Bicyclic 1,3a,6a-Triazapentalene Chromophores: Synthesis, Spectroscopy and Their Use as Fluorescent Sensors and Probes

: The 1,3a,6a-triazapentalene (TAP) is an aromatic heterocyclic fluorescent dye with interesting features such as its small size, large Stokes shift, solvatochromism, and emission wavelengths that are spread across the visible spectrum. TAPs have been synthesized via different synthetic strategies involving click − cyclization − aromatization domino reactions, gold-catalyzed cyclization of propargyl triazoles or triazolization of acetophenones. As a result, TAPs with diverse substitution patterns were obtained, showing varying fluorescence properties. Based on these properties, several TAPs have been selected and studied as fluorescent imaging probes in living cells and as sensors. This mini review provides an overview of the research on the bicyclic TAPs and does not comment on the literature about benzo or otherwise fused systems. The synthetic methodologies for the preparation of TAPs, the substituent effects on the fluorescence properties, and the behavior of the TAP core as an element of biological imaging probes and sensors are discussed.

The bicyclic TAPs, which are the subject of this mini review, have been prepared via different synthetic pathways.Hirobe et al. were the first to report the bicyclic (non-fused) triazapentalenes in 1978 [26].However, during the decades that followed, this heterocyclic scaffold was somehow not further studied, until a reappearance was made in 2011 [17].Namba et al. cleverly applied the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction for the synthesis of the parent TAPs, which resulted in a number of valuable studies published by this group throughout the past decade [27][28][29][30].Furthermore, these findings also encouraged other researchers to study the TAP fluorophore and to develop alternative methods for their preparation [31,32].
In this mini review, we will cover the different synthetic methods toward bicyclic triazapentalenes, along with the photophysical data and applications of the respective dyes.Throughout the remaining part of this text, TAP will only refer to bicyclic, non-aryl-fused triazapentalenes.

Synthetic Methods and Spectroscopic Properties 2.1. Aminopyrazole-Mediated Syntheses
The bicyclic 1,3a,6a-triazapentalenes, firstly reported by the Hirobe group, were synthesized via two different reaction pathways (Scheme 1) [26].One pathway involved the synthesis of 3-acetyl-2-methyl-TAP 4. Starting from the parent pyrazole 1 and hydroxylamine-O-sulfonic acid 2, 1-aminopyrazole 3 was prepared and further reacted with 3-chloropentane-2,4-dione at elevated temperatures.In the next step, the resulting TAP 4 could be deacetylated under acidic conditions to afford the colorless 2-methyl-TAP 5 in the 95% yield.In another pathway, the 2-phenyl-TAP derivative 8 was synthesized through the amination of phenacylpyrazole 7 with O-(mesitylenesulfonyl)hydroxylamine 6.Interestingly, the deacetylated TAP 5 appeared to be sensitive to air and distinctly less stable compared to the 3-acyl derivative 4. The 2-phenyl-TAP 8 was slightly more stable than its methyl analog 5. From this initial study, the authors already recognized the stabilizing effect of an electron withdrawing group on the TAP core.much less described, and this is why we will not include them in this literature study.However, we should mention a recent (2020) synthetic method based on intramolecular N-N bond formation of pyrazole-substituted aminopyridines and aminodiazines in the presence of hypervalent iodine(III) leading to tricyclic TAP derivatives with fluorescent behavior, that was published by Suzenet et al. [25].This is a very interesting new development in TAP chemistry.
The bicyclic TAPs, which are the subject of this mini review, have been prepared via different synthetic pathways.Hirobe et al. were the first to report the bicyclic (non-fused) triazapentalenes in 1978 [26].However, during the decades that followed, this heterocyclic scaffold was somehow not further studied, until a reappearance was made in 2011 [17].Namba et al. cleverly applied the copper-catalyzed azide-alkyne cycloaddition (Cu-AAC) reaction for the synthesis of the parent TAPs, which resulted in a number of valuable studies published by this group throughout the past decade [27][28][29][30].Furthermore, these findings also encouraged other researchers to study the TAP fluorophore and to develop alternative methods for their preparation [31,32].
In this mini review, we will cover the different synthetic methods toward bicyclic triazapentalenes, along with the photophysical data and applications of the respective dyes.Throughout the remaining part of this text, TAP will only refer to bicyclic, non-arylfused triazapentalenes.

Aminopyrazole-Mediated Syntheses
The bicyclic 1,3a,6a-triazapentalenes, firstly reported by the Hirobe group, were synthesized via two different reaction pathways (Scheme 1) [26].One pathway involved the synthesis of 3-acetyl-2-methyl-TAP 4. Starting from the parent pyrazole 1 and hydroxylamine-O-sulfonic acid 2, 1-aminopyrazole 3 was prepared and further reacted with 3-chloropentane-2,4-dione at elevated temperatures.In the next step, the resulting TAP 4 could be deacetylated under acidic conditions to afford the colorless 2-methyl-TAP 5 in the 95% yield.In another pathway, the 2-phenyl-TAP derivative 8 was synthesized through the amination of phenacylpyrazole 7 with O-(mesitylenesulfonyl)hydroxylamine 6.Interestingly, the deacetylated TAP 5 appeared to be sensitive to air and distinctly less stable compared to the 3-acyl derivative 4. The 2-phenyl-TAP 8 was slightly more stable than its methyl analog 5. From this initial study, the authors already recognized the stabilizing effect of an electron withdrawing group on the TAP core.

CuAAC-Based Syntheses
Namba et al. envisioned the renowned copper-click reaction as a valuable tool for the preparation of TAPs [17].Starting from terminal alkynes 9 and 1-azidopropane building blocks 10 containing leaving groups (LG) at positions 2 and 3, the azide-alkyne cycloaddition in the presence of catalytic Cu(I) provided 1,2,3-triazoles as intermediate substrates.

CuAAC-Based Syntheses
Namba et al. envisioned the renowned copper-click reaction as a valuable tool for the preparation of TAPs [17].Starting from terminal alkynes 9 and 1-azidopropane building blocks 10 containing leaving groups (LG) at positions 2 and 3, the azide-alkyne cycloaddition in the presence of catalytic Cu(I) provided 1,2,3-triazoles as intermediate substrates.
Next, cyclization of the 1,2,3-triazoles easily occurred in the basic environment via the substitution of one leaving group and was followed by the elimination of the second leaving group, causing aromatization (Scheme 2).Normally, the substituents on the azidopropanes were trifluoromethanesulfonate (triflate) groups.By changing the substituents on the alkynes and introducing additional side groups on the azido substrates, 3-unsubstituted TAP derivatives with various functionalization patterns were obtained by means of this general reaction pathway.
substitution of one leaving group and was followed by the elimination of the second leaving group, causing aromatization (Scheme 2).Normally, the substituents on the azidopropanes were trifluoromethanesulfonate (triflate) groups.By changing the substituents on the alkynes and introducing additional side groups on the azido substrates, 3-unsubstituted TAP derivatives with various functionalization patterns were obtained by means of this general reaction pathway.Scheme 2. CuAAC-based synthesis of 3-unsubstituted TAPs 11.

The 2-Substituted 1,3a,6a-Triazapentalenes
Various 2-substituted TAPs 12 were synthesized by the Namba group starting from terminal alkynes 9 and 3-azido-propane-1,2-diyl bistriflate 10a (Scheme 3) [17,28].The reactions were carried out with copper(I) iodide, bis[2-(N,N-dimethylamino)ethyl] ether (BDMAEE) ligand and triethylamine (TEA) base in tetrahydrofuran (THF).It was found that the presence of an electron withdrawing group at the C2 position led to better reaction yields.Whereas the reaction with 4-nitrophenylacetylene reached a 96% yield of TAP 12g, TAP 12d with a 4-methoxyphenyl substituent was only obtained with a yield of 56%.Intriguingly, the unsubstituted triazapentalene 12b was obtained for the first time by the direct desilylation of crude 2-trimethylsilyl-TAP 12a.However, TAPs lacking an aryl substituent and 4-methoxyphenyl-TAP 12d gradually decomposed under UV irradiation.Therefore, it was confirmed that an electron poor aryl group is needed to stabilize the TAP core.
Scheme 3. The synthesis of 2-substituted TAPs 12 and the parent TAP 12b.
The fluorescent properties of TAPs were investigated by Namba et al. already in this first report and in subsequent articles.As indicated in Table 1, it was clear that the emission maxima of 2-substituted TAP in dichloromethane (DCM) underwent a bathochromic shift as the Hammett σp value of the para substituted phenyl groups increased from −0.28 to 0.81 (Table 1) [17,28].As a result of introducing additional electron withdrawing groups on the aryl group, compounds 12i and 12j exhibited bathochromically shifted yellow and red fluorescence, respectively [28].Moreover, the Stokes shifts of these 2-substituted TAPs were between 83 and 166 nm, which are rather large values.Notably, compounds 12f and 12i showed a strong positive solvatochromism as the emission maxima increased with 72 nm and 99 nm, respectively, when changing the solvent from benzene to acetone.The trends based on the Hammett values and the solvatochromic effect might be of use to predict the emission wavelengths of TAPs with other substituents at position 2 and in different solvents.Unfortunately, the quantum yields of the fluorescence of most 2-substituted TAPs were rather low (3-44%).The fluorescent properties of TAPs were investigated by Namba et al. already in this first report and in subsequent articles.As indicated in Table 1, it was clear that the emission maxima of 2-substituted TAP in dichloromethane (DCM) underwent a bathochromic shift as the Hammett σ p value of the para substituted phenyl groups increased from −0.28 to 0.81 (Table 1) [17,28].As a result of introducing additional electron withdrawing groups on the aryl group, compounds 12i and 12j exhibited bathochromically shifted yellow and red fluorescence, respectively [28].Moreover, the Stokes shifts of these 2-substituted TAPs were between 83 and 166 nm, which are rather large values.Notably, compounds 12f and 12i showed a strong positive solvatochromism as the emission maxima increased with 72 nm and 99 nm, respectively, when changing the solvent from benzene to acetone.The trends based on the Hammett values and the solvatochromic effect might be of use to predict the emission wavelengths of TAPs with other substituents at position 2 and in different solvents.Unfortunately, the quantum yields of the fluorescence of most 2-substituted TAPs were rather low (3-44%).The 2,5-disubstituted 1,3a,6a-triazapentalenes were prep dure by using 2-substituted 3-azido-2-methoxypropyl triflat aromatization failed when using triethylamine as the base.In DBU as a stronger base or in an acidic environment, eliminatio not happen.However, the elimination occurred by using KH substituted TAPs 13 were obtained successfully (Scheme 4) [2 were good, except for the examples with a phenyl group at t a 4-nitrophenyl substituent at position 2 (13i).Note that the pared without heating to reflux temperature or by using lith spectively.An interesting observation was that the quantum yields o dramatically increased as a result of introducing a functional 2-cyanophenyl-TAP 12f, as shown in Table 2 [27].Moreover the C5 position had no obvious effect on the emission wavel duction of a 5-cyano group that caused a hypsochromic effec emission wavelengths.When changing the aryl substituent a 5-methyl-TAPs, the quantum yields substantially increased w increased from 0 to 0.71, as shown in Table 3.For the 4-meth the 4-nitrophenyl (σp = 0.81) substituents, the quantum yiel respectively.Thus, for some examples, a relation could be no  The 2,5-disubstituted 1,3a,6a-triazapentalenes were prepared via the general procedure by using 2-substituted 3-azido-2-methoxypropyl triflates 10b [27].In this case, the aromatization failed when using triethylamine as the base.In addition, in the presence of DBU as a stronger base or in an acidic environment, elimination of the methoxy group did not happen.However, the elimination occurred by using KHMDS at −78 °C, and 2,5-disubstituted TAPs 13 were obtained successfully (Scheme 4) [27].Nearly all reaction yields were good, except for the examples with a phenyl group at the C5 position (13d) or with a 4-nitrophenyl substituent at position 2 (13i).Note that the latter derivatives were prepared without heating to reflux temperature or by using lithium diethylamide base, respectively.An interesting observation was that the quantum yields of fluorescence for 13ad were dramatically increased as a result of introducing a functional group at the C5 position of 2-cyanophenyl-TAP 12f, as shown in Table 2 [27].Moreover, these functional groups at the C5 position had no obvious effect on the emission wavelengths, except for the introduction of a 5-cyano group that caused a hypsochromic effect on both the absorption and emission wavelengths.When changing the aryl substituent at the C2 position of different 5-methyl-TAPs, the quantum yields substantially increased when the Hammett values σp increased from 0 to 0.71, as shown in Table 3.For the 4-methoxyphenyl (σp = −0.28)and the 4-nitrophenyl (σp = 0.81) substituents, the quantum yields were only 0.02 and 0.03, respectively.Thus, for some examples, a relation could be noticed between the quantum yield of 2-arylated 5-methyl-TAPs and the Hammett parameter of the phenyl substituent.The 2,5-disubstituted 1,3a,6a-triazapentalenes were prepared via the general procedure by using 2-substituted 3-azido-2-methoxypropyl triflates 10b [27].In this case, the aromatization failed when using triethylamine as the base.In addition, in the presence of DBU as a stronger base or in an acidic environment, elimination of the methoxy group did not happen.However, the elimination occurred by using KHMDS at −78 °C, and 2,5-disubstituted TAPs 13 were obtained successfully (Scheme 4) [27].Nearly all reaction yields were good, except for the examples with a phenyl group at the C5 position (13d) or with a 4-nitrophenyl substituent at position 2 (13i).Note that the latter derivatives were prepared without heating to reflux temperature or by using lithium diethylamide base, respectively.An interesting observation was that the quantum yields of fluorescence for 13ad were dramatically increased as a result of introducing a functional group at the C5 position of 2-cyanophenyl-TAP 12f, as shown in Table 2 [27].Moreover, these functional groups at the C5 position had no obvious effect on the emission wavelengths, except for the introduction of a 5-cyano group that caused a hypsochromic effect on both the absorption and emission wavelengths.When changing the aryl substituent at the C2 position of different 5-methyl-TAPs, the quantum yields substantially increased when the Hammett values σp increased from 0 to 0.71, as shown in Table 3.For the 4-methoxyphenyl (σp = −0.28)and the 4-nitrophenyl (σp = 0.81) substituents, the quantum yields were only 0.02 and 0.03, respectively.Thus, for some examples, a relation could be noticed between the quantum yield of 2-arylated 5-methyl-TAPs and the Hammett parameter of the phenyl substituent.The 2,5-disubstituted 1,3a,6a-triazapentalenes were prepared via the general procedure by using 2-substituted 3-azido-2-methoxypropyl triflates 10b [27].In this case, the aromatization failed when using triethylamine as the base.In addition, in the presence of DBU as a stronger base or in an acidic environment, elimination of the methoxy group did not happen.However, the elimination occurred by using KHMDS at −78 °C, and 2,5-disubstituted TAPs 13 were obtained successfully (Scheme 4) [27].Nearly all reaction yields were good, except for the examples with a phenyl group at the C5 position (13d) or with a 4-nitrophenyl substituent at position 2 (13i).Note that the latter derivatives were prepared without heating to reflux temperature or by using lithium diethylamide base, respectively.An interesting observation was that the quantum yields of fluorescence for 13ad were dramatically increased as a result of introducing a functional group at the C5 position of 2-cyanophenyl-TAP 12f, as shown in Table 2 [27].Moreover, these functional groups at the C5 position had no obvious effect on the emission wavelengths, except for the introduction of a 5-cyano group that caused a hypsochromic effect on both the absorption and emission wavelengths.When changing the aryl substituent at the C2 position of different 5-methyl-TAPs, the quantum yields substantially increased when the Hammett values σp increased from 0 to 0.71, as shown in Table 3.For the 4-methoxyphenyl (σp = −0.28)and the 4-nitrophenyl (σp = 0.81) substituents, the quantum yields were only 0.02 and 0.03, respectively.Thus, for some examples, a relation could be noticed between the quantum yield of 2-arylated 5-methyl-TAPs and the Hammett parameter of the phenyl substituent.The 2,5-disubstituted 1,3a,6a-triazapentalenes were prepared via the general procedure by using 2-substituted 3-azido-2-methoxypropyl triflates 10b [27].In this case, the aromatization failed when using triethylamine as the base.In addition, in the presence of DBU as a stronger base or in an acidic environment, elimination of the methoxy group did not happen.However, the elimination occurred by using KHMDS at −78 °C, and 2,5-disubstituted TAPs 13 were obtained successfully (Scheme 4) [27].Nearly all reaction yields were good, except for the examples with a phenyl group at the C5 position (13d) or with a 4-nitrophenyl substituent at position 2 (13i).Note that the latter derivatives were prepared without heating to reflux temperature or by using lithium diethylamide base, respectively.An interesting observation was that the quantum yields of fluorescence for 13ad were dramatically increased as a result of introducing a functional group at the C5 position of 2-cyanophenyl-TAP 12f, as shown in Table 2 [27].Moreover, these functional groups at the C5 position had no obvious effect on the emission wavelengths, except for the introduction of a 5-cyano group that caused a hypsochromic effect on both the absorption and emission wavelengths.When changing the aryl substituent at the C2 position of different 5-methyl-TAPs, the quantum yields substantially increased when the Hammett values σp increased from 0 to 0.71, as shown in Table 3.For the 4-methoxyphenyl (σp = −0.28)and the 4-nitrophenyl (σp = 0.81) substituents, the quantum yields were only 0.02 and 0.03, respectively.Thus, for some examples, a relation could be noticed between the quantum yield of 2-arylated 5-methyl-TAPs and the Hammett parameter of the phenyl substituent.The 2,5-disubstituted 1,3a,6a-triazapentalenes were prepared via the general procedure by using 2-substituted 3-azido-2-methoxypropyl triflates 10b [27].In this case, the aromatization failed when using triethylamine as the base.In addition, in the presence of DBU as a stronger base or in an acidic environment, elimination of the methoxy group did not happen.However, the elimination occurred by using KHMDS at −78 °C, and 2,5-disubstituted TAPs 13 were obtained successfully (Scheme 4) [27].Nearly all reaction yields were good, except for the examples with a phenyl group at the C5 position (13d) or with a 4-nitrophenyl substituent at position 2 (13i).Note that the latter derivatives were prepared without heating to reflux temperature or by using lithium diethylamide base, respectively.An interesting observation was that the quantum yields of fluorescence for 13ad were dramatically increased as a result of introducing a functional group at the C5 position of 2-cyanophenyl-TAP 12f, as shown in Table 2 [27].Moreover, these functional groups at the C5 position had no obvious effect on the emission wavelengths, except for the introduction of a 5-cyano group that caused a hypsochromic effect on both the absorption and emission wavelengths.When changing the aryl substituent at the C2 position of different 5-methyl-TAPs, the quantum yields substantially increased when the Hammett values σp increased from 0 to 0.71, as shown in Table 3.For the 4-methoxyphenyl (σp = −0.28)and the 4-nitrophenyl (σp = 0.81) substituents, the quantum yields were only 0.02 and 0.03, respectively.Thus, for some examples, a relation could be noticed between the quantum yield of 2-arylated 5-methyl-TAPs and the Hammett parameter of the phenyl substituent.The 2,5-disubstituted 1,3a,6a-triazapentalenes were prepared via the general procedure by using 2-substituted 3-azido-2-methoxypropyl triflates 10b [27].In this case, the aromatization failed when using triethylamine as the base.In addition, in the presence of DBU as a stronger base or in an acidic environment, elimination of the methoxy group did not happen.However, the elimination occurred by using KHMDS at −78 °C, and 2,5-disubstituted TAPs 13 were obtained successfully (Scheme 4) [27].Nearly all reaction yields were good, except for the examples with a phenyl group at the C5 position (13d) or with a 4-nitrophenyl substituent at position 2 (13i).Note that the latter derivatives were prepared without heating to reflux temperature or by using lithium diethylamide base, respectively.An interesting observation was that the quantum yields of fluorescence for 13ad were dramatically increased as a result of introducing a functional group at the C5 position of 2-cyanophenyl-TAP 12f, as shown in Table 2 [27].Moreover, these functional groups at the C5 position had no obvious effect on the emission wavelengths, except for the introduction of a 5-cyano group that caused a hypsochromic effect on both the absorption and emission wavelengths.When changing the aryl substituent at the C2 position of different 5-methyl-TAPs, the quantum yields substantially increased when the Hammett values σp increased from 0 to 0.71, as shown in Table 3.For the 4-methoxyphenyl (σp = −0.28)and the 4-nitrophenyl (σp = 0.81) substituents, the quantum yields were only 0.02 and 0.03, respectively.Thus, for some examples, a relation could be noticed between the quantum yield of 2-arylated 5-methyl-TAPs and the Hammett parameter of the phenyl substituent.The 2,5-disubstituted 1,3a,6a-triazapentalenes were prepared via the general procedure by using 2-substituted 3-azido-2-methoxypropyl triflates 10b [27].In this case, the aromatization failed when using triethylamine as the base.In addition, in the presence of DBU as a stronger base or in an acidic environment, elimination of the methoxy group did not happen.However, the elimination occurred by using KHMDS at −78 °C, and 2,5-disubstituted TAPs 13 were obtained successfully (Scheme 4) [27].Nearly all reaction yields were good, except for the examples with a phenyl group at the C5 position (13d) or with a 4-nitrophenyl substituent at position 2 (13i).Note that the latter derivatives were prepared without heating to reflux temperature or by using lithium diethylamide base, respectively.An interesting observation was that the quantum yields of fluorescence for 13ad were dramatically increased as a result of introducing a functional group at the C5 position of 2-cyanophenyl-TAP 12f, as shown in Table 2 [27].Moreover, these functional groups at the C5 position had no obvious effect on the emission wavelengths, except for the introduction of a 5-cyano group that caused a hypsochromic effect on both the absorption and emission wavelengths.When changing the aryl substituent at the C2 position of different 5-methyl-TAPs, the quantum yields substantially increased when the Hammett values σp increased from 0 to 0.71, as shown in Table 3.For the 4-methoxyphenyl (σp = −0.28)and the 4-nitrophenyl (σp = 0.81) substituents, the quantum yields were only 0.02 and 0.03, respectively.Thus, for some examples, a relation could be noticed between the quantum yield of 2-arylated 5-methyl-TAPs and the Hammett parameter of the phenyl substituent.The 2,5-disubstituted 1,3a,6a-triazapentalenes were prepared via the general procedure by using 2-substituted 3-azido-2-methoxypropyl triflates 10b [27].In this case, the aromatization failed when using triethylamine as the base.In addition, in the presence of DBU as a stronger base or in an acidic environment, elimination of the methoxy group did not happen.However, the elimination occurred by using KHMDS at −78 °C, and 2,5-disubstituted TAPs 13 were obtained successfully (Scheme 4) [27].Nearly all reaction yields were good, except for the examples with a phenyl group at the C5 position (13d) or with a 4-nitrophenyl substituent at position 2 (13i).Note that the latter derivatives were prepared without heating to reflux temperature or by using lithium diethylamide base, respectively.An interesting observation was that the quantum yields of fluorescence for 13ad were dramatically increased as a result of introducing a functional group at the C5 position of 2-cyanophenyl-TAP 12f, as shown in Table 2 [27].Moreover, these functional groups at the C5 position had no obvious effect on the emission wavelengths, except for the introduction of a 5-cyano group that caused a hypsochromic effect on both the absorption and emission wavelengths.When changing the aryl substituent at the C2 position of different 5-methyl-TAPs, the quantum yields substantially increased when the Hammett values σp increased from 0 to 0.71, as shown in Table 3.For the 4-methoxyphenyl (σp = −0.28)and the 4-nitrophenyl (σp = 0.81) substituents, the quantum yields were only 0.02 and 0.03, respectively.Thus, for some examples, a relation could be noticed between the quantum yield of 2-arylated 5-methyl-TAPs and the Hammett parameter of the phenyl substituent.The 2,5-disubstituted 1,3a,6a-triazapentalenes were prepared via the general procedure by using 2-substituted 3-azido-2-methoxypropyl triflates 10b [27].In this case, the aromatization failed when using triethylamine as the base.In addition, in the presence of DBU as a stronger base or in an acidic environment, elimination of the methoxy group did not happen.However, the elimination occurred by using KHMDS at −78 • C, and 2,5-disubstituted TAPs 13 were obtained successfully (Scheme 4) [27].Nearly all reaction yields were good, except for the examples with a phenyl group at the C5 position (13d) or with a 4-nitrophenyl substituent at position 2 (13i).Note that the latter derivatives were prepared without heating to reflux temperature or by using lithium diethylamide base, respectively.The 2,5-disubstituted 1,3a,6a-triazapentalenes were prepared via the general procedure by using 2-substituted 3-azido-2-methoxypropyl triflates 10b [27].In this case, the aromatization failed when using triethylamine as the base.In addition, in the presence of DBU as a stronger base or in an acidic environment, elimination of the methoxy group did not happen.However, the elimination occurred by using KHMDS at −78 °C, and 2,5-disubstituted TAPs 13 were obtained successfully (Scheme 4) [27].Nearly all reaction yields were good, except for the examples with a phenyl group at the C5 position (13d) or with a 4-nitrophenyl substituent at position 2 (13i).Note that the latter derivatives were prepared without heating to reflux temperature or by using lithium diethylamide base, respectively.An interesting observation was that the quantum yields of fluorescence for 13ad were dramatically increased as a result of introducing a functional group at the C5 position of 2-cyanophenyl-TAP 12f, as shown in Table 2 [27].Moreover, these functional groups at the C5 position had no obvious effect on the emission wavelengths, except for the introduction of a 5-cyano group that caused a hypsochromic effect on both the absorption and emission wavelengths.When changing the aryl substituent at the C2 position of different 5-methyl-TAPs, the quantum yields substantially increased when the Hammett values σp increased from 0 to 0.71, as shown in Table 3.For the 4-methoxyphenyl (σp = −0.28)and the 4-nitrophenyl (σp = 0.81) substituents, the quantum yields were only 0.02 and 0.03, respectively.Thus, for some examples, a relation could be noticed between the quantum yield of 2-arylated 5-methyl-TAPs and the Hammett parameter of the phenyl substituent.An interesting observation was that the quantum yields of fluorescence for 13ad were dramatically increased as a result of introducing a functional group at the C5 position of 2-cyanophenyl-TAP 12f, as shown in Table 2 [27].Moreover, these functional groups at the C5 position had no obvious effect on the emission wavelengths, except for the introduction of a 5-cyano group that caused a hypsochromic effect on both the absorption and emission wavelengths.When changing the aryl substituent at the C2 position of different 5-methyl-TAPs, the quantum yields substantially increased when the Hammett values σ p increased from 0 to 0.71, as shown in Table 3.For the 4-methoxyphenyl (σ p = −0.28)and the 4-nitrophenyl (σ p = 0.81) substituents, the quantum yields were only 0.02 and 0.03, respectively.Thus, for some examples, a relation could be noticed between the quantum yield of 2-arylated 5-methyl-TAPs and the Hammett parameter of the phenyl substituent.The 2,5-disubstituted 1,3a,6a-triazapentalenes were prepared via the general procedure by using 2-substituted 3-azido-2-methoxypropyl triflates 10b [27].In this case, the aromatization failed when using triethylamine as the base.In addition, in the presence of DBU as a stronger base or in an acidic environment, elimination of the methoxy group did not happen.However, the elimination occurred by using KHMDS at −78 °C, and 2,5-disubstituted TAPs 13 were obtained successfully (Scheme 4) [27].Nearly all reaction yields were good, except for the examples with a phenyl group at the C5 position (13d) or with a 4-nitrophenyl substituent at position 2 (13i).Note that the latter derivatives were prepared without heating to reflux temperature or by using lithium diethylamide base, respectively.An interesting observation was that the quantum yields of fluorescence for 13ad were dramatically increased as a result of introducing a functional group at the C5 position of 2-cyanophenyl-TAP 12f, as shown in Table 2 [27].Moreover, these functional groups at the C5 position had no obvious effect on the emission wavelengths, except for the introduction of a 5-cyano group that caused a hypsochromic effect on both the absorption and emission wavelengths.When changing the aryl substituent at the C2 position of different 5-methyl-TAPs, the quantum yields substantially increased when the Hammett values σp increased from 0 to 0.71, as shown in Table 3.For the 4-methoxyphenyl (σp = −0.28)and the 4-nitrophenyl (σp = 0.81) substituents, the quantum yields were only 0.02 and 0.03, respectively.Thus, for some examples, a relation could be noticed between the quantum yield of 2-arylated 5-methyl-TAPs and the Hammett parameter of the phenyl substituent.To investigate the effect of substituents at the C4 position, various 4-methyl and phenyl-TAP analogs were synthesized by the Namba group (Scheme 5) [29].The yields the 4-methyl-TAP analogs were more variable (19-94%) (Table 4).On the other hand, t 4-phenyl-TAPs were obtained in moderate-to-high yields (50-88%) (Table 5).For som derivatives, the low yields were attributed to decomposition during purification.To e pand the scope of 4-methyl-TAP analogs, 1,4-diethynylbenzene 9b and cyclic strained a kyne 9c were applied to synthesize 14a and 14b, respectively, via the reaction with 3-a ido-3-methylpropane-1,2-diyl bistriflate.The designed compound 14a was not obtain as the reaction stopped after the mono-TAP was formed.This intermediate was readi decomposed during purification.Compound 14b was obtained successfully in 49% yie via the general procedure but without the use of a copper catalyst.For comparison, simil reactions were carried out to afford the corresponding 4-unsubstituted TAPs 12k and 1 in 46% and 51% yields, respectively.To investigate the effect of substituents at the C4 position, various 4-methyl and 4phenyl-TAP analogs were synthesized by the Namba group (Scheme 5) [29].The yields of the 4-methyl-TAP analogs were more variable (19-94%) (Table 4).On the other hand, the 4-phenyl-TAPs were obtained in moderate-to-high yields (50-88%) (Table 5).For some derivatives, the low yields were attributed to decomposition during purification.To expand the scope of 4-methyl-TAP analogs, 1,4-diethynylbenzene 9b and cyclic strained alkyne 9c were applied to synthesize 14a and 14b, respectively, via the reaction with 3-azido-3-methylpropane-1,2-diyl bistriflate.The designed compound 14a was not obtained as the reaction stopped after the mono-TAP was formed.This intermediate was readily decomposed during purification.Compound 14b was obtained successfully in 49% yield via the general procedure but without the use of a copper catalyst.For comparison, similar reactions were carried out to afford the corresponding 4-unsubstituted TAPs 12k and 12l in 46% and 51% yields, respectively.To investigate the effect of substituents at the C4 position, various 4-methyl and 4phenyl-TAP analogs were synthesized by the Namba group (Scheme 5) [29].The yields of the 4-methyl-TAP analogs were more variable (19-94%) (Table 4).On the other hand, the 4-phenyl-TAPs were obtained in moderate-to-high yields (50-88%) (Table 5).For some derivatives, the low yields were attributed to decomposition during purification.To expand the scope of 4-methyl-TAP analogs, 1,4-diethynylbenzene 9b and cyclic strained alkyne 9c were applied to synthesize 14a and 14b, respectively, via the reaction with 3-azido-3-methylpropane-1,2-diyl bistriflate.The designed compound 14a was not obtained as the reaction stopped after the mono-TAP was formed.This intermediate was readily decomposed during purification.Compound 14b was obtained successfully in 49% yield via the general procedure but without the use of a copper catalyst.For comparison, similar reactions were carried out to afford the corresponding 4-unsubstituted TAPs 12k and 12l in 46% and 51% yields, respectively.To investigate the effect of substituents at the C4 position, various 4-methyl and 4phenyl-TAP analogs were synthesized by the Namba group (Scheme 5) [29].The yields of the 4-methyl-TAP analogs were more variable (19-94%) (Table 4).On the other hand, the 4-phenyl-TAPs were obtained in moderate-to-high yields (50-88%) (Table 5).For some derivatives, the low yields were attributed to decomposition during purification.To expand the scope of 4-methyl-TAP analogs, 1,4-diethynylbenzene 9b and cyclic strained alkyne 9c were applied to synthesize 14a and 14b, respectively, via the reaction with 3-azido-3-methylpropane-1,2-diyl bistriflate.The designed compound 14a was not obtained as the reaction stopped after the mono-TAP was formed.This intermediate was readily decomposed during purification.Compound 14b was obtained successfully in 49% yield via the general procedure but without the use of a copper catalyst.For comparison, similar reactions were carried out to afford the corresponding 4-unsubstituted TAPs 12k and 12l in 46% and 51% yields, respectively.To investigate the effect of substituents at the C4 position, various 4-methyl and 4phenyl-TAP analogs were synthesized by the Namba group (Scheme 5) [29].The yields of the 4-methyl-TAP analogs were more variable (19-94%) (Table 4).On the other hand, the 4-phenyl-TAPs were obtained in moderate-to-high yields (50-88%) (Table 5).For some derivatives, the low yields were attributed to decomposition during purification.To expand the scope of 4-methyl-TAP analogs, 1,4-diethynylbenzene 9b and cyclic strained alkyne 9c were applied to synthesize 14a and 14b, respectively, via the reaction with 3-azido-3-methylpropane-1,2-diyl bistriflate.The designed compound 14a was not obtained as the reaction stopped after the mono-TAP was formed.This intermediate was readily decomposed during purification.Compound 14b was obtained successfully in 49% yield via the general procedure but without the use of a copper catalyst.For comparison, similar reactions were carried out to afford the corresponding 4-unsubstituted TAPs 12k and 12l in 46% and 51% yields, respectively.To investigate the effect of substituents at the C4 position, various 4-methyl and 4phenyl-TAP analogs were synthesized by the Namba group (Scheme 5) [29].The yields of the 4-methyl-TAP analogs were more variable (19-94%) (Table 4).On the other hand, the 4-phenyl-TAPs were obtained in moderate-to-high yields (50-88%) (Table 5).For some derivatives, the low yields were attributed to decomposition during purification.To expand the scope of 4-methyl-TAP analogs, 1,4-diethynylbenzene 9b and cyclic strained alkyne 9c were applied to synthesize 14a and 14b, respectively, via the reaction with 3-azido-3-methylpropane-1,2-diyl bistriflate.The designed compound 14a was not obtained as the reaction stopped after the mono-TAP was formed.This intermediate was readily decomposed during purification.Compound 14b was obtained successfully in 49% yield via the general procedure but without the use of a copper catalyst.For comparison, similar reactions were carried out to afford the corresponding 4-unsubstituted TAPs 12k and 12l in 46% and 51% yields, respectively.To investigate the effect of substituents at the C4 position, various 4-methyl and 4phenyl-TAP analogs were synthesized by the Namba group (Scheme 5) [29].The yields of the 4-methyl-TAP analogs were more variable (19-94%) (Table 4).On the other hand, the 4-phenyl-TAPs were obtained in moderate-to-high yields (50-88%) (Table 5).For some derivatives, the low yields were attributed to decomposition during purification.To expand the scope of 4-methyl-TAP analogs, 1,4-diethynylbenzene 9b and cyclic strained alkyne 9c were applied to synthesize 14a and 14b, respectively, via the reaction with 3-azido-3-methylpropane-1,2-diyl bistriflate.The designed compound 14a was not obtained as the reaction stopped after the mono-TAP was formed.This intermediate was readily decomposed during purification.Compound 14b was obtained successfully in 49% yield via the general procedure but without the use of a copper catalyst.For comparison, similar reactions were carried out to afford the corresponding 4-unsubstituted TAPs 12k and 12l in 46% and 51% yields, respectively.To investigate the effect of substituents at the C4 position, various 4-methyl and 4phenyl-TAP analogs were synthesized by the Namba group (Scheme 5) [29].The yields of the 4-methyl-TAP analogs were more variable (19-94%) (Table 4).On the other hand, the 4-phenyl-TAPs were obtained in moderate-to-high yields (50-88%) (Table 5).For some derivatives, the low yields were attributed to decomposition during purification.To expand the scope of 4-methyl-TAP analogs, 1,4-diethynylbenzene 9b and cyclic strained alkyne 9c were applied to synthesize 14a and 14b, respectively, via the reaction with 3-azido-3-methylpropane-1,2-diyl bistriflate.The designed compound 14a was not obtained as the reaction stopped after the mono-TAP was formed.This intermediate was readily decomposed during purification.Compound 14b was obtained successfully in 49% yield via the general procedure but without the use of a copper catalyst.For comparison, similar reactions were carried out to afford the corresponding 4-unsubstituted TAPs 12k and 12l in 46% and 51% yields, respectively.Interestingly, the emission maxima of 4-phenyl-TAP (such as 14m, λem,max = 61 and 4-methyl-TAP (such as 14e, λem,max = 611 nm) analogs were similar to each othe Therefore, it could be concluded that the expansion of π-conjugation between the C nyl and TAP core did not show an effect on the emission wavelength.To compare w unsubstituted TAPs, the extinction coefficient (ε) values of 4-phenyl analogs were ured at slightly longer absorption wavelengths and larger ε values were observed, may enhance the brightness as for 14j and 14k (Table 5).Remarkably, both a meth phenyl group at the C4 position could induce a redshift of the maximum emission length.To obtain the 2,6-disubstituted TAPs, the initial plan was to use the general dure starting from 3-azido-1-methylpropane-1,2-diyl bistriflates and terminal al However, the methylazidoditriflate was not stable enough to prepare.In 2013, Nam al. reported a Payne-type rearrangement of 1-(oxiranylmethyl)-1,2,3-triazoles [33].on this earlier study, a reported procedure was developed for the synthesis of 2,6stituted 1,3a,6a-triazapentalenes 21.The intermediate 20 was formed by the triflic mediated epoxide-opening reaction, then followed by the subsequent reactions of lation and base-induced elimination (Scheme 6) [30].Due to the poor stability of methyl-substituted TAPs, all reaction yields were relatively low (Table 6), while the stable 6-(methoxycarbonyl)-TAP 23 was obtained in 40% yield.On the other hand, phenyl-TAP was not obtained after attempts under various conditions.Interestingly, the emission maxima of 4-phenyl-TAP (such as 14m, λem,max = 613 nm) and 4-methyl-TAP (such as 14e, λem,max = 611 nm) analogs were similar to each other [29].Therefore, it could be concluded that the expansion of π-conjugation between the C4 phenyl and TAP core did not show an effect on the emission wavelength.To compare with 4unsubstituted TAPs, the extinction coefficient (ε) values of 4-phenyl analogs were measured at slightly longer absorption wavelengths and larger ε values were observed, which may enhance the brightness as for 14j and 14k (Table 5).Remarkably, both a methyl and phenyl group at the C4 position could induce a redshift of the maximum emission wavelength.To obtain the 2,6-disubstituted TAPs, the initial plan was to use the general procedure starting from 3-azido-1-methylpropane-1,2-diyl bistriflates and terminal alkynes.However, the methylazidoditriflate was not stable enough to prepare.In 2013, Namba et al. reported a Payne-type rearrangement of 1-(oxiranylmethyl)-1,2,3-triazoles [33].Based on this earlier study, a reported procedure was developed for the synthesis of 2,6-disubstituted 1,3a,6a-triazapentalenes 21.The intermediate 20 was formed by the triflic acidmediated epoxide-opening reaction, then followed by the subsequent reactions of acetylation and base-induced elimination (Scheme 6) [30].Due to the poor stability of the 6methyl-substituted TAPs, all reaction yields were relatively low (Table 6), while the more stable 6-(methoxycarbonyl)-TAP 23 was obtained in 40% yield.On the other hand, the 6phenyl-TAP was not obtained after attempts under various conditions.Interestingly, the emission maxima of 4-phenyl-TAP (such as 14m, λem,max = 613 nm) and 4-methyl-TAP (such as 14e, λem,max = 611 nm) analogs were similar to each other [29].Therefore, it could be concluded that the expansion of π-conjugation between the C4 phenyl and TAP core did not show an effect on the emission wavelength.To compare with 4unsubstituted TAPs, the extinction coefficient (ε) values of 4-phenyl analogs were measured at slightly longer absorption wavelengths and larger ε values were observed, which may enhance the brightness as for 14j and 14k (Table 5).Remarkably, both a methyl and phenyl group at the C4 position could induce a redshift of the maximum emission wavelength.To obtain the 2,6-disubstituted TAPs, the initial plan was to use the general procedure starting from 3-azido-1-methylpropane-1,2-diyl bistriflates and terminal alkynes.However, the methylazidoditriflate was not stable enough to prepare.In 2013, Namba et al. reported a Payne-type rearrangement of 1-(oxiranylmethyl)-1,2,3-triazoles [33].Based on this earlier study, a reported procedure was developed for the synthesis of 2,6-disubstituted 1,3a,6a-triazapentalenes 21.The intermediate 20 was formed by the triflic acidmediated epoxide-opening reaction, then followed by the subsequent reactions of acetylation and base-induced elimination (Scheme 6) [30].Due to the poor stability of the 6methyl-substituted TAPs, all reaction yields were relatively low (Table 6), while the more stable 6-(methoxycarbonyl)-TAP 23 was obtained in 40% yield.On the other hand, the 6phenyl-TAP was not obtained after attempts under various conditions.Interestingly, the emission maxima of 4-phenyl-TAP (such as 14m, λem,max = 613 nm) and 4-methyl-TAP (such as 14e, λem,max = 611 nm) analogs were similar to each other [29].Therefore, it could be concluded that the expansion of π-conjugation between the C4 phenyl and TAP core did not show an effect on the emission wavelength.To compare with 4unsubstituted TAPs, the extinction coefficient (ε) values of 4-phenyl analogs were measured at slightly longer absorption wavelengths and larger ε values were observed, which may enhance the brightness as for 14j and 14k (Table 5).Remarkably, both a methyl and phenyl group at the C4 position could induce a redshift of the maximum emission wavelength.To obtain the 2,6-disubstituted TAPs, the initial plan was to use the general procedure starting from 3-azido-1-methylpropane-1,2-diyl bistriflates and terminal alkynes.However, the methylazidoditriflate was not stable enough to prepare.In 2013, Namba et al. reported a Payne-type rearrangement of 1-(oxiranylmethyl)-1,2,3-triazoles [33].Based on this earlier study, a reported procedure was developed for the synthesis of 2,6-disubstituted 1,3a,6a-triazapentalenes 21.The intermediate 20 was formed by the triflic acidmediated epoxide-opening reaction, then followed by the subsequent reactions of acetylation and base-induced elimination (Scheme 6) [30].Due to the poor stability of the 6methyl-substituted TAPs, all reaction yields were relatively low (Table 6), while the more stable 6-(methoxycarbonyl)-TAP 23 was obtained in 40% yield.On the other hand, the 6phenyl-TAP was not obtained after attempts under various conditions.Interestingly, the emission maxima of 4-phenyl-TAP (such as 14m, λem,max = 613 nm) and 4-methyl-TAP (such as 14e, λem,max = 611 nm) analogs were similar to each other [29].Therefore, it could be concluded that the expansion of π-conjugation between the C4 phenyl and TAP core did not show an effect on the emission wavelength.To compare with 4unsubstituted TAPs, the extinction coefficient (ε) values of 4-phenyl analogs were measured at slightly longer absorption wavelengths and larger ε values were observed, which may enhance the brightness as for 14j and 14k (Table 5).Remarkably, both a methyl and phenyl group at the C4 position could induce a redshift of the maximum emission wavelength.To obtain the 2,6-disubstituted TAPs, the initial plan was to use the general procedure starting from 3-azido-1-methylpropane-1,2-diyl bistriflates and terminal alkynes.However, the methylazidoditriflate was not stable enough to prepare.In 2013, Namba et al. reported a Payne-type rearrangement of 1-(oxiranylmethyl)-1,2,3-triazoles [33].Based on this earlier study, a reported procedure was developed for the synthesis of 2,6-disubstituted 1,3a,6a-triazapentalenes 21.The intermediate 20 was formed by the triflic acidmediated epoxide-opening reaction, then followed by the subsequent reactions of acetylation and base-induced elimination (Scheme 6) [30].Due to the poor stability of the 6methyl-substituted TAPs, all reaction yields were relatively low (Table 6), while the more stable 6-(methoxycarbonyl)-TAP 23 was obtained in 40% yield.On the other hand, the 6phenyl-TAP was not obtained after attempts under various conditions.Interestingly, the emission maxima of 4-phenyl-TAP (such as 14m, λem,max = 613 nm) and 4-methyl-TAP (such as 14e, λem,max = 611 nm) analogs were similar to each other [29].Therefore, it could be concluded that the expansion of π-conjugation between the C4 phenyl and TAP core did not show an effect on the emission wavelength.To compare with 4unsubstituted TAPs, the extinction coefficient (ε) values of 4-phenyl analogs were measured at slightly longer absorption wavelengths and larger ε values were observed, which may enhance the brightness as for 14j and 14k (Table 5).Remarkably, both a methyl and phenyl group at the C4 position could induce a redshift of the maximum emission wavelength.To obtain the 2,6-disubstituted TAPs, the initial plan was to use the general procedure starting from 3-azido-1-methylpropane-1,2-diyl bistriflates and terminal alkynes.However, the methylazidoditriflate was not stable enough to prepare.In 2013, Namba et al. reported a Payne-type rearrangement of 1-(oxiranylmethyl)-1,2,3-triazoles [33].Based on this earlier study, a reported procedure was developed for the synthesis of 2,6-disubstituted 1,3a,6a-triazapentalenes 21.The intermediate 20 was formed by the triflic acidmediated epoxide-opening reaction, then followed by the subsequent reactions of acetylation and base-induced elimination (Scheme 6) [30].Due to the poor stability of the 6methyl-substituted TAPs, all reaction yields were relatively low (Table 6), while the more stable 6-(methoxycarbonyl)-TAP 23 was obtained in 40% yield.On the other hand, the 6phenyl-TAP was not obtained after attempts under various conditions.Interestingly, the emission maxima of 4-phenyl-TAP (such as 14m, λ em,max = 613 nm) and 4-methyl-TAP (such as 14e, λ em,max = 611 nm) analogs were similar to each other [29].Therefore, it could be concluded that the expansion of π-conjugation between the C4 phenyl and TAP core did not show an effect on the emission wavelength.To compare with 4-unsubstituted TAPs, the extinction coefficient (ε) values of 4-phenyl analogs were measured at slightly longer absorption wavelengths and larger ε values were observed, which may enhance the brightness as for 14j and 14k (Table 5).Remarkably, both a methyl and phenyl group at the C4 position could induce a redshift of the maximum emission wavelength.Interestingly, the emission maxima of 4-phenyl-TAP (such as 14m, λem,max = 613 and 4-methyl-TAP (such as 14e, λem,max = 611 nm) analogs were similar to each other Therefore, it could be concluded that the expansion of π-conjugation between the C4 nyl and TAP core did not show an effect on the emission wavelength.To compare w unsubstituted TAPs, the extinction coefficient (ε) values of 4-phenyl analogs were m ured at slightly longer absorption wavelengths and larger ε values were observed, w may enhance the brightness as for 14j and 14k (Table 5).Remarkably, both a methy phenyl group at the C4 position could induce a redshift of the maximum emission w length.

The 2,6-Disubstituted 1,3a,6a-Triazapentalenes
To obtain the 2,6-disubstituted TAPs, the initial plan was to use the general p dure starting from 3-azido-1-methylpropane-1,2-diyl bistriflates and terminal alk However, the methylazidoditriflate was not stable enough to prepare.In 2013, Nam al. reported a Payne-type rearrangement of 1-(oxiranylmethyl)-1,2,3-triazoles [33].B on this earlier study, a reported procedure was developed for the synthesis of 2,6-d stituted 1,3a,6a-triazapentalenes 21.The intermediate 20 was formed by the triflic mediated epoxide-opening reaction, then followed by the subsequent reactions of a lation and base-induced elimination (Scheme 6) [30].Due to the poor stability of t methyl-substituted TAPs, all reaction yields were relatively low (Table 6), while the stable 6-(methoxycarbonyl)-TAP 23 was obtained in 40% yield.On the other hand, phenyl-TAP was not obtained after attempts under various conditions.Interestingly, the emission maxima of 4-phenyl-TAP (such as 14m, λem,max = 613 nm) and 4-methyl-TAP (such as 14e, λem,max = 611 nm) analogs were similar to each other [29].Therefore, it could be concluded that the expansion of π-conjugation between the C4 phenyl and TAP core did not show an effect on the emission wavelength.To compare with 4unsubstituted TAPs, the extinction coefficient (ε) values of 4-phenyl analogs were measured at slightly longer absorption wavelengths and larger ε values were observed, which may enhance the brightness as for 14j and 14k (Table 5).Remarkably, both a methyl and phenyl group at the C4 position could induce a redshift of the maximum emission wavelength.

The 2,6-Disubstituted 1,3a,6a-Triazapentalenes
To obtain the 2,6-disubstituted TAPs, the initial plan was to use the general procedure starting from 3-azido-1-methylpropane-1,2-diyl bistriflates and terminal alkynes.However, the methylazidoditriflate was not stable enough to prepare.In 2013, Namba et al. reported a Payne-type rearrangement of 1-(oxiranylmethyl)-1,2,3-triazoles [33].Based on this earlier study, a reported procedure was developed for the synthesis of 2,6-disubstituted 1,3a,6a-triazapentalenes 21.The intermediate 20 was formed by the triflic acidmediated epoxide-opening reaction, then followed by the subsequent reactions of acetylation and base-induced elimination (Scheme 6) [30].Due to the poor stability of the 6methyl-substituted TAPs, all reaction yields were relatively low (Table 6), while the more stable 6-(methoxycarbonyl)-TAP 23 was obtained in 40% yield.On the other hand, the 6phenyl-TAP was not obtained after attempts under various conditions.Interestingly, the emission maxima of 4-phenyl-TAP (such as 14m, λem,max = 613 nm) and 4-methyl-TAP (such as 14e, λem,max = 611 nm) analogs were similar to each other [29].Therefore, it could be concluded that the expansion of π-conjugation between the C4 phenyl and TAP core did not show an effect on the emission wavelength.To compare with 4unsubstituted TAPs, the extinction coefficient (ε) values of 4-phenyl analogs were measured at slightly longer absorption wavelengths and larger ε values were observed, which may enhance the brightness as for 14j and 14k (Table 5).Remarkably, both a methyl and phenyl group at the C4 position could induce a redshift of the maximum emission wavelength.

The 2,6-Disubstituted 1,3a,6a-Triazapentalenes
To obtain the 2,6-disubstituted TAPs, the initial plan was to use the general procedure starting from 3-azido-1-methylpropane-1,2-diyl bistriflates and terminal alkynes.However, the methylazidoditriflate was not stable enough to prepare.In 2013, Namba et al. reported a Payne-type rearrangement of 1-(oxiranylmethyl)-1,2,3-triazoles [33].Based on this earlier study, a reported procedure was developed for the synthesis of 2,6-disubstituted 1,3a,6a-triazapentalenes 21.The intermediate 20 was formed by the triflic acidmediated epoxide-opening reaction, then followed by the subsequent reactions of acetylation and base-induced elimination (Scheme 6) [30].Due to the poor stability of the 6methyl-substituted TAPs, all reaction yields were relatively low (Table 6), while the more stable 6-(methoxycarbonyl)-TAP 23 was obtained in 40% yield.On the other hand, the 6phenyl-TAP was not obtained after attempts under various conditions.Interestingly, the emission maxima of 4-phenyl-TAP (such as 14m, λem,max = 613 nm) and 4-methyl-TAP (such as 14e, λem,max = 611 nm) analogs were similar to each other [29].Therefore, it could be concluded that the expansion of π-conjugation between the C4 phenyl and TAP core did not show an effect on the emission wavelength.To compare with 4unsubstituted TAPs, the extinction coefficient (ε) values of 4-phenyl analogs were measured at slightly longer absorption wavelengths and larger ε values were observed, which may enhance the brightness as for 14j and 14k (Table 5).Remarkably, both a methyl and phenyl group at the C4 position could induce a redshift of the maximum emission wavelength.

The 2,6-Disubstituted 1,3a,6a-Triazapentalenes
To obtain the 2,6-disubstituted TAPs, the initial plan was to use the general procedure starting from 3-azido-1-methylpropane-1,2-diyl bistriflates and terminal alkynes.However, the methylazidoditriflate was not stable enough to prepare.In 2013, Namba et al. reported a Payne-type rearrangement of 1-(oxiranylmethyl)-1,2,3-triazoles [33].Based on this earlier study, a reported procedure was developed for the synthesis of 2,6-disubstituted 1,3a,6a-triazapentalenes 21.The intermediate 20 was formed by the triflic acidmediated epoxide-opening reaction, then followed by the subsequent reactions of acetylation and base-induced elimination (Scheme 6) [30].Due to the poor stability of the 6methyl-substituted TAPs, all reaction yields were relatively low (Table 6), while the more stable 6-(methoxycarbonyl)-TAP 23 was obtained in 40% yield.On the other hand, the 6phenyl-TAP was not obtained after attempts under various conditions.Interestingly, the emission maxima of 4-phenyl-TAP (such as 14m, λem,max = 613 nm) and 4-methyl-TAP (such as 14e, λem,max = 611 nm) analogs were similar to each other [29].Therefore, it could be concluded that the expansion of π-conjugation between the C4 phenyl and TAP core did not show an effect on the emission wavelength.To compare with 4unsubstituted TAPs, the extinction coefficient (ε) values of 4-phenyl analogs were measured at slightly longer absorption wavelengths and larger ε values were observed, which may enhance the brightness as for 14j and 14k (Table 5).Remarkably, both a methyl and phenyl group at the C4 position could induce a redshift of the maximum emission wavelength.

The 2,6-Disubstituted 1,3a,6a-Triazapentalenes
To obtain the 2,6-disubstituted TAPs, the initial plan was to use the general procedure starting from 3-azido-1-methylpropane-1,2-diyl bistriflates and terminal alkynes.However, the methylazidoditriflate was not stable enough to prepare.In 2013, Namba et al. reported a Payne-type rearrangement of 1-(oxiranylmethyl)-1,2,3-triazoles [33].Based on this earlier study, a reported procedure was developed for the synthesis of 2,6-disubstituted 1,3a,6a-triazapentalenes 21.The intermediate 20 was formed by the triflic acidmediated epoxide-opening reaction, then followed by the subsequent reactions of acetylation and base-induced elimination (Scheme 6) [30].Due to the poor stability of the 6methyl-substituted TAPs, all reaction yields were relatively low (Table 6), while the more stable 6-(methoxycarbonyl)-TAP 23 was obtained in 40% yield.On the other hand, the 6phenyl-TAP was not obtained after attempts under various conditions.Interestingly, the emission maxima of 4-phenyl-TAP (such as 14m, λem,max = 613 nm) and 4-methyl-TAP (such as 14e, λem,max = 611 nm) analogs were similar to each other [29].Therefore, it could be concluded that the expansion of π-conjugation between the C4 phenyl and TAP core did not show an effect on the emission wavelength.To compare with 4unsubstituted TAPs, the extinction coefficient (ε) values of 4-phenyl analogs were measured at slightly longer absorption wavelengths and larger ε values were observed, which may enhance the brightness as for 14j and 14k (Table 5).Remarkably, both a methyl and phenyl group at the C4 position could induce a redshift of the maximum emission wavelength.

The 2,6-Disubstituted 1,3a,6a-Triazapentalenes
To obtain the 2,6-disubstituted TAPs, the initial plan was to use the general procedure starting from 3-azido-1-methylpropane-1,2-diyl bistriflates and terminal alkynes.However, the methylazidoditriflate was not stable enough to prepare.In 2013, Namba et al. reported a Payne-type rearrangement of 1-(oxiranylmethyl)-1,2,3-triazoles [33].Based on this earlier study, a reported procedure was developed for the synthesis of 2,6-disubstituted 1,3a,6a-triazapentalenes 21.The intermediate 20 was formed by the triflic acidmediated epoxide-opening reaction, then followed by the subsequent reactions of acetylation and base-induced elimination (Scheme 6) [30].Due to the poor stability of the 6methyl-substituted TAPs, all reaction yields were relatively low (Table 6), while the more stable 6-(methoxycarbonyl)-TAP 23 was obtained in 40% yield.On the other hand, the 6phenyl-TAP was not obtained after attempts under various conditions.Interestingly, the emission maxima of 4-phenyl-TAP (such as 14m, λem,max = 613 nm) and 4-methyl-TAP (such as 14e, λem,max = 611 nm) analogs were similar to each other [29].Therefore, it could be concluded that the expansion of π-conjugation between the C4 phenyl and TAP core did not show an effect on the emission wavelength.To compare with 4unsubstituted TAPs, the extinction coefficient (ε) values of 4-phenyl analogs were measured at slightly longer absorption wavelengths and larger ε values were observed, which may enhance the brightness as for 14j and 14k (Table 5).Remarkably, both a methyl and phenyl group at the C4 position could induce a redshift of the maximum emission wavelength.
Introducing the methyl group at the C6 position of 2-substituted 1,3a,6atriazapentalenes not only induced a long-wavelength shift of the emission maxima but also affected the quantum yields (Table 6) [30].Nearly all the quantum yields were somewhat increased, except for compounds 21d and 21e.Notably, the methoxycarbonyl group at the C6 position ( 23) quenched the fluorescence.It was assumed that the electron withdrawing group disturbed the charge transfer between the TAP core and C2 substituents.a Absorption maximum of the corresponding 6-unsubstituted analog.b Fluorescence maximum of the corresponding 6unsubstituted analog.c Quantum yield of corresponding to the 6-unsubstituted analog.

Gold-Catalyzed Cyclization of Propargyl-1,2,3-Triazoles
In 2010, Shi et al. reported an efficient method to synthesize propargyl-1,2,3-triazoles 24 via the iron-catalyzed alkylation with propargyl alcohols and found that the N2-substituted propargyl triazoles 24 could be further transformed via the intramolecular goldcatalyzed triazole-yne cyclization (Scheme 7) [34].Later in 2014, the same group demonstrated that this cyclization resulted in the formation of TAPs 27 by using propargyl triazoles 24 bearing an electron withdrawing group (Scheme 7) [31].The electron withdrawing group on the triazole ring, mainly ketones and esters, changed the electron density distribution of the intermediate bicyclic system.This electron density redistribution induced an effective regioselection followed by protodeauration to afford differently substituted triazapentalenes 27.In general, ester-substituted TAPs were obtained in slightly lower yields.However, the diester-substituted TAPs were shown to form in high yields (over 80%).Furthermore, starting from mono ester-substituted TAPs, 3-unsubstituted TAPs were obtained via LiOH-induced saponification/decarboxylation.Introducing the methyl group at the C6 position of 2-substituted 1,3a,6a-triazapentalenes not only induced a long-wavelength shift of the emission maxima but also affected the quantum yields (Table 6) [30].Nearly all the quantum yields were somewhat increased, except for compounds 21d and 21e.Notably, the methoxycarbonyl group at the C6 position ( 23) quenched the fluorescence.It was assumed that the electron withdrawing group disturbed the charge transfer between the TAP core and C2 substituents.Introducing the methyl group at the C6 position of 2-substituted 1,3a,6atriazapentalenes not only induced a long-wavelength shift of the emission maxima but also affected the quantum yields (Table 6) [30].Nearly all the quantum yields were somewhat increased, except for compounds 21d and 21e.Notably, the methoxycarbonyl group at the C6 position ( 23) quenched the fluorescence.It was assumed that the electron withdrawing group disturbed the charge transfer between the TAP core and C2 substituents.a Absorption maximum of the corresponding 6-unsubstituted analog.b Fluorescence maximum of the corresponding 6unsubstituted analog.c Quantum yield of corresponding to the 6-unsubstituted analog.

Gold-Catalyzed Cyclization of Propargyl-1,2,3-Triazoles
In 2010, Shi et al. reported an efficient method to synthesize propargyl-1,2,3-triazoles 24 via the iron-catalyzed alkylation with propargyl alcohols and found that the N2-substituted propargyl triazoles 24 could be further transformed via the intramolecular goldcatalyzed triazole-yne cyclization (Scheme 7) [34].Later in 2014, the same group demonstrated that this cyclization resulted in the formation of TAPs 27 by using propargyl triazoles 24 bearing an electron withdrawing group (Scheme 7) [31].The electron withdrawing group on the triazole ring, mainly ketones and esters, changed the electron density distribution of the intermediate bicyclic system.This electron density redistribution induced an effective regioselection followed by protodeauration to afford differently substituted triazapentalenes 27.In general, ester-substituted TAPs were obtained in slightly lower yields.However, the diester-substituted TAPs were shown to form in high yields (over 80%).Furthermore, starting from mono ester-substituted TAPs, 3-unsubstituted TAPs were obtained via LiOH-induced saponification/decarboxylation.Introducing the methyl group at the C6 position of 2-substituted 1,3a,6atriazapentalenes not only induced a long-wavelength shift of the emission maxima but also affected the quantum yields (Table 6) [30].Nearly all the quantum yields were somewhat increased, except for compounds 21d and 21e.Notably, the methoxycarbonyl group at the C6 position (23) quenched the fluorescence.It was assumed that the electron withdrawing group disturbed the charge transfer between the TAP core and C2 substituents.
a Absorption maximum of the corresponding 6-unsubstituted analog.b Fluorescence maximum of the corresponding 6unsubstituted analog.c Quantum yield of corresponding to the 6-unsubstituted analog.

Gold-Catalyzed Cyclization of Propargyl-1,2,3-Triazoles
In 2010, Shi et al. reported an efficient method to synthesize propargyl-1,2,3-triazoles 24 via the iron-catalyzed alkylation with propargyl alcohols and found that the N2-substituted propargyl triazoles 24 could be further transformed via the intramolecular goldcatalyzed triazole-yne cyclization (Scheme 7) [34].Later in 2014, the same group demonstrated that this cyclization resulted in the formation of TAPs 27 by using propargyl triazoles 24 bearing an electron withdrawing group (Scheme 7) [31].The electron withdrawing group on the triazole ring, mainly ketones and esters, changed the electron density distribution of the intermediate bicyclic system.This electron density redistribution induced an effective regioselection followed by protodeauration to afford differently substituted triazapentalenes 27.In general, ester-substituted TAPs were obtained in slightly lower yields.However, the diester-substituted TAPs were shown to form in high yields (over 80%).Furthermore, starting from mono ester-substituted TAPs, 3-unsubstituted TAPs were obtained via LiOH-induced saponification/decarboxylation.
Introducing the methyl group at the C6 position of 2-substituted 1,3a,6atriazapentalenes not only induced a long-wavelength shift of the emission maxima but also affected the quantum yields (Table 6) [30].Nearly all the quantum yields were somewhat increased, except for compounds 21d and 21e.Notably, the methoxycarbonyl group at the C6 position (23) quenched the fluorescence.It was assumed that the electron withdrawing group disturbed the charge transfer between the TAP core and C2 substituents.
a Absorption maximum of the corresponding 6-unsubstituted analog.b Fluorescence maximum of the corresponding 6unsubstituted analog.c Quantum yield of corresponding to the 6-unsubstituted analog.

Gold-Catalyzed Cyclization of Propargyl-1,2,3-Triazoles
In 2010, Shi et al. reported an efficient method to synthesize propargyl-1,2,3-triazoles 24 via the iron-catalyzed alkylation with propargyl alcohols and found that the N2-substituted propargyl triazoles 24 could be further transformed via the intramolecular goldcatalyzed triazole-yne cyclization (Scheme 7) [34].Later in 2014, the same group demonstrated that this cyclization resulted in the formation of TAPs 27 by using propargyl triazoles 24 bearing an electron withdrawing group (Scheme 7) [31].The electron withdrawing group on the triazole ring, mainly ketones and esters, changed the electron density distribution of the intermediate bicyclic system.This electron density redistribution induced an effective regioselection followed by protodeauration to afford differently substituted triazapentalenes 27.In general, ester-substituted TAPs were obtained in slightly lower yields.However, the diester-substituted TAPs were shown to form in high yields (over 80%).Furthermore, starting from mono ester-substituted TAPs, 3-unsubstituted TAPs were obtained via LiOH-induced saponification/decarboxylation.
Introducing the methyl group at the C6 position of 2-substituted 1,3a,6atriazapentalenes not only induced a long-wavelength shift of the emission maxima but also affected the quantum yields (Table 6) [30].Nearly the quantum yields were somewhat increased, except for compounds 21d and 21e.Notably, the methoxycarbonyl group at the C6 position (23) the fluorescence.It was assumed that the electron withdrawing group disturbed the charge transfer between TAP core and C2 a Absorption maximum of the corresponding 6-unsubstituted analog.b Fluorescence maximum of the corresponding 6unsubstituted analog.c Quantum yield of corresponding to the 6-unsubstituted analog.

Gold-Catalyzed Cyclization of Propargyl-1,2,3-Triazoles
In 2010, Shi et al. reported an efficient method to synthesize propargyl-1,2,3-triazoles 24 via the iron-catalyzed alkylation with propargyl alcohols and found that the N2-substituted propargyl triazoles 24 could be further transformed via the intramolecular goldcatalyzed triazole-yne cyclization (Scheme 7) [34].Later in 2014, the same group demonstrated that this cyclization resulted in the formation of TAPs 27 by using propargyl triazoles 24 bearing an electron withdrawing group (Scheme 7) [31].The electron withdrawing group on the triazole ring, mainly ketones and esters, changed the electron density distribution of the intermediate bicyclic system.This electron density redistribution induced an effective regioselection followed by protodeauration to afford differently substituted triazapentalenes 27.In general, ester-substituted TAPs were obtained in slightly lower yields.However, the diester-substituted TAPs were shown to form in high yields (over 80%).Furthermore, starting from mono ester-substituted TAPs, 3-unsubstituted TAPs were obtained via LiOH-induced saponification/decarboxylation.
Introducing the methyl group at the C6 position of 2-substituted 1,3a,6atriazapentalenes not only induced a long-wavelength shift of the emission maxima but also affected the quantum yields (Table 6) [30].Nearly all the quantum yields were somewhat increased, except for compounds 21d and 21e.Notably, the methoxycarbonyl group at the C6 position (23) quenched the fluorescence.It was assumed that the electron withdrawing group disturbed the charge transfer between the TAP core and C2 substituents.
a Absorption maximum of the corresponding 6-unsubstituted analog.b Fluorescence maximum of the corresponding 6unsubstituted analog.c Quantum yield of corresponding to the 6-unsubstituted analog.

Gold-Catalyzed Cyclization of Propargyl-1,2,3-Triazoles
In 2010, Shi et al. reported an efficient method to synthesize propargyl-1,2,3-triazoles 24 via the iron-catalyzed alkylation with propargyl alcohols and found that the N2-substituted propargyl triazoles 24 could be further transformed via the intramolecular goldcatalyzed triazole-yne cyclization (Scheme 7) [34].Later in 2014, the same group demonstrated that this cyclization resulted in the formation of TAPs 27 by using propargyl triazoles 24 bearing an electron withdrawing group (Scheme 7) [31].The electron withdrawing group on the triazole ring, mainly ketones and esters, changed the electron density distribution of the intermediate bicyclic system.This electron density redistribution induced an effective regioselection followed by protodeauration to afford differently substituted triazapentalenes 27.In general, ester-substituted TAPs were obtained in slightly lower yields.However, the diester-substituted TAPs were shown to form in high yields (over 80%).Furthermore, starting from mono ester-substituted TAPs, 3-unsubstituted TAPs were obtained via LiOH-induced saponification/decarboxylation.
a Absorption maximum of the corresponding 6-unsubstituted analog.b Fluorescence maximum of the corresponding 6-unsubstituted analog.c Quantum yield of corresponding to the 6-unsubstituted analog.

Gold-Catalyzed Cyclization of Propargyl-1,2,3-Triazoles
In 2010, Shi et al. reported an efficient method to synthesize propargyl-1,2,3-triazoles 24 via the iron-catalyzed alkylation with propargyl alcohols and found that the N2substituted propargyl triazoles 24 could be further transformed via the intramolecular gold-catalyzed triazole-yne cyclization (Scheme 7) [34].Later in 2014, the same group demonstrated that this cyclization resulted in the formation of TAPs 27 by using propargyl triazoles 24 bearing an electron withdrawing group (Scheme 7) [31].The electron withdrawing group on the triazole ring, mainly ketones and esters, changed the electron density distribution of the intermediate bicyclic system.This electron density redistribution induced an effective regioselection followed by protodeauration to afford differently substituted triazapentalenes 27.In general, ester-substituted TAPs were obtained in slightly lower yields.However, the diester-substituted TAPs were shown to form in high yields (over 80%).Furthermore, starting from mono ester-substituted TAPs, 3-unsubstituted TAPs were obtained via LiOH-induced saponification/decarboxylation.
Compared to previous methods, this two-step pathway started from commercially available compounds and there was no need for toxic transition metal catalysts.However, only TAPs with electron poor aryl groups at the C3 position were successfully obtained.
The fluorescence properties of 3-substituted TAPs were studied in acetonitrile, DCM and toluene [32].Surprisingly, compound 31a with a 4-nitrophenyl group at the C3 position showed no fluorescence, which was different from its fluorescent isomer 2-(4-nitrophenyl)-triazapentalene 12g.In contrast with the other 3-aryl-TAPs 31, compound 31a exhibited a longer absorption maximum wavelength and a broader absorption peak (Table 7).These properties of 31a might be due to the intramolecular charge transfer caused by the nitro group.Compared to the 2-cyanophenyl TAP 12f, the Stokes shift of compound 31b (63 nm) was relatively small in DCM, but the quantum yield of fluorescence was quite high (57%).The Stokes shifts of compounds 31b and 31c increased as the polarity of the solvent increased, and the full widths at half maximum of emission of compounds 31b and 31c were similar to each other.Remarkably, the quantum yield of the fluorescence of compound 31c was 79% in DCM, which was the highest quantum yield measured so far for any TAP derivative, although this was a lot less in the polar solvent acetonitrile (4%).
Compared to previous methods, this two-step pathway started from commercially available compounds and there was no need for toxic transition metal catalysts.However, only TAPs with electron poor aryl groups at the C3 position were successfully obtained.
The fluorescence properties of 3-substituted TAPs were studied in acetonitrile, DCM and toluene [32].Surprisingly, compound 31a with a 4-nitrophenyl group at the C3 position showed no fluorescence, which was different from its fluorescent isomer 2-(4-nitrophenyl)-triazapentalene 12g.In contrast with the other 3-aryl-TAPs 31, compound 31a exhibited a longer absorption maximum wavelength and a broader absorption peak (Table 7).These properties of 31a might be due to the intramolecular charge transfer caused by the nitro group.Compared to the 2-cyanophenyl TAP 12f, the Stokes shift of compound 31b (63 nm) was relatively small in DCM, but the quantum yield of fluorescence was quite high (57%).The Stokes shifts of compounds 31b and 31c increased as the polarity of the solvent increased, and the full widths at half maximum of emission of compounds 31b and 31c were similar to each other.Remarkably, the quantum yield of the fluorescence of compound 31c was 79% in DCM, which was the highest quantum yield measured so far for any TAP derivative, although this was a lot less in the polar solvent acetonitrile (4%).Compared to previous methods, this two-step pathway started from commercially available compounds and there was no need for toxic transition metal catalysts.However, only TAPs with electron poor aryl groups at the C3 position were successfully obtained.
The fluorescence properties of 3-substituted TAPs were studied in acetonitrile, DCM and toluene [32].Surprisingly, compound 31a with a 4-nitrophenyl group at the C3 position showed no fluorescence, which was different from its fluorescent isomer 2-(4-nitrophenyl)triazapentalene 12g.In contrast with the other 3-aryl-TAPs 31, compound 31a exhibited a longer absorption maximum wavelength and a broader absorption peak (Table 7).These properties of 31a might be due to the intramolecular charge transfer caused by the nitro group.Compared to the 2-cyanophenyl TAP 12f, the Stokes shift of compound 31b (63 nm) was relatively small in DCM, but the quantum yield of fluorescence was quite high (57%).The Stokes shifts of compounds 31b and 31c increased as the polarity of the solvent increased, and the full widths at half maximum of emission of compounds 31b and 31c were similar to each other.Remarkably, the quantum yield of the fluorescence of compound 31c was 79% in DCM, which was the highest quantum yield measured so far for any TAP derivative, although this was a lot less in the polar solvent acetonitrile (4%).

Acetylation and Nitrosation
Although 2-substituted TAPs 5 and 8 were sensitive to air, acetylation and nitrosation of these compounds could be carried out.The TAPs reacted at the C3 position, resulting in 3-acetyl and 3-nitroso derivatives in high yields (Scheme 9) [26].The successful electrophilic substitution reactions clearly demonstrated the electron rich nature of the TAP core.

Linearly Bonded 1,3a,6a-Triazapentalene Dimers and Trimer
Starting from the azidotriflate 33 with protected alkyne function, a 2,5-disubstituted TAP with tert-butyldimethylsilyl ether (TBS) protecting group was synthesized via click reaction followed by cyclization.The azidotriflate 33 was prepared via a multistep synthesis [36].After removing the TBS group, the monoethyl-substituted triazapentalene 34 was applied as the starting material together with one more equivalent of 33 in a reiteration of this TAP formation, to develop the linearly bonded oligomeric systems 35 (Scheme 10) [36].The TAP dimers (n = 2) with different substituents at the C2 position were reported by the Namba group, including a 2-unsubstituted TAP dimer.Unfortunately, the TAP trimers (n = 3) were, in general, too difficult to obtain due to decomposition during the elimination reactions (Table 8).An exception was the derivative with a tridecyl group at the C2 position.
The properties of TAP monomers, TAP dimers, and the TAP trimer were rather similar in the diluted solution in DCM, showing that introducing additional TAP rings had no drastic effect on the fluorescence characteristics [36].Interestingly, the linearly bonded TAP dimer 35 (n = 2, R = Ph) showed different fluorescence properties when varying the concentration, which suggested changes in the aggregation state.The phenyl-TAP-dimer showed mechanochromic fluorescence in the solid phase and a fluorescence wavelength redshift while going from the crystalline to the amorphous state upon grinding.Emission lifetimes were determined for the solid dimer 35 (n = 2, R = Ph) at 540 nm before (λem,max = 535 nm) and after grinding (λem,max = 590 nm), and were found to be 4.9 and 1.2, respectively.Notably, density functional theory (DFT) calculations verified the planar form of trimer-TAP (R = C13H27).

Acetylation and Nitrosation
Although 2-substituted TAPs 5 and 8 were sensitive to air, acetylation and nitrosation of these compounds could be carried out.The TAPs reacted at the C3 position, resulting in 3-acetyl and 3-nitroso derivatives in high yields (Scheme 9) [26].The successful electrophilic substitution reactions clearly demonstrated the electron rich nature of the TAP core.

Linearly Bonded 1,3a,6a-Triazapentalene Dimers and Trimer
Starting from the azidotriflate 33 with protected alkyne function, a 2,5-disubstituted TAP with tert-butyldimethylsilyl ether (TBS) protecting group was synthesized via click reaction followed by cyclization.The azidotriflate 33 was prepared via a multistep synthesis [36].After removing the TBS group, the monoethyl-substituted triazapentalene 34 was applied as the starting material together with one more equivalent of 33 in a reiteration of this TAP formation, to develop the linearly bonded oligomeric systems 35 (Scheme 10) [36].The TAP dimers (n = 2) with different substituents at the C2 position were reported by the Namba group, including a 2-unsubstituted TAP dimer.Unfortunately, the TAP trimers (n = 3) were, in general, too difficult to obtain due to decomposition during the elimination reactions (Table 8).An exception was the derivative with a tridecyl group at the C2 position.
The properties of TAP monomers, TAP dimers, and the TAP trimer were rather similar in the diluted solution in DCM, showing that introducing additional TAP rings had no drastic effect on the fluorescence characteristics [36].Interestingly, the linearly bonded TAP dimer 35 (n = 2, R = Ph) showed different fluorescence properties when varying the concentration, which suggested changes in the aggregation state.The phenyl-TAP-dimer showed mechanochromic fluorescence in the solid phase and a fluorescence wavelength redshift while going from the crystalline to the amorphous state upon grinding.Emission lifetimes were determined for the solid dimer 35 (n = 2, R = Ph) at 540 nm before (λem,max = 535 nm) and after grinding (λem,max = 590 nm), and were found to be 4.9 and 1.2, respectively.Notably, density functional theory (DFT) calculations verified the planar form of trimer-TAP (R = C13H27).

Acetylation and Nitrosation
Although 2-substituted TAPs 5 and 8 were sensitive to air, acetylation and nitrosation of these compounds could be carried out.The TAPs reacted at the C3 position, resulting in 3-acetyl and 3-nitroso derivatives in high yields (Scheme 9) [26].The successful electrophilic substitution reactions clearly demonstrated the electron rich nature of the TAP core.

Linearly Bonded 1,3a,6a-Triazapentalene Dimers and Trimer
Starting from the azidotriflate 33 with protected alkyne function, a 2,5-disubstituted TAP with tert-butyldimethylsilyl ether (TBS) protecting group was synthesized via click reaction followed by cyclization.The azidotriflate 33 was prepared via a multistep synthesis [36].After removing the TBS group, the monoethyl-substituted triazapentalene 34 was applied as the starting material together with one more equivalent of 33 in a reiteration of this TAP formation, to develop the linearly bonded oligomeric systems 35 (Scheme 10) [36].The TAP dimers (n = 2) with different substituents at the C2 position were reported by the Namba group, including a 2-unsubstituted TAP dimer.Unfortunately, the TAP trimers (n = 3) were, in general, too difficult to obtain due to decomposition during the elimination reactions (Table 8).An exception was the derivative with a tridecyl group at the C2 position.
The properties of TAP monomers, TAP dimers, and the TAP trimer were rather similar in the diluted solution in DCM, showing that introducing additional TAP rings had no drastic effect on the fluorescence characteristics [36].Interestingly, the linearly bonded TAP dimer 35 (n = 2, R = Ph) showed different fluorescence properties when varying the concentration, which suggested changes in the aggregation state.The phenyl-TAP-dimer showed mechanochromic fluorescence in the solid phase and a fluorescence wavelength redshift while going from the crystalline to the amorphous state upon grinding.Emission lifetimes were determined for the solid dimer 35 (n = 2, R = Ph) at 540 nm before (λem,max = 535 nm) and after grinding (λem,max = 590 nm), and were found to be 4.9 and 1.2, respectively.Notably, density functional theory (DFT) calculations verified the planar form of trimer-TAP (R = C13H27).

Acetylation and Nitrosation
Although 2-substituted TAPs 5 and 8 were sensitive to air, acetylation and nitrosation of these compounds could be carried out.The TAPs reacted at the C3 position, resulting in 3-acetyl and 3-nitroso derivatives in high yields (Scheme 9) [26].The successful electrophilic substitution reactions clearly demonstrated the electron rich nature of the TAP core.

Linearly Bonded 1,3a,6a-Triazapentalene Dimers and Trimer
Starting from the azidotriflate 33 with protected alkyne function, a 2,5-disubstituted TAP with tert-butyldimethylsilyl ether (TBS) protecting group was synthesized via click reaction followed by cyclization.The azidotriflate 33 was prepared via a multistep synthesis [36].After removing the TBS group, the monoethyl-substituted triazapentalene 34 was applied as the starting material together with one more equivalent of 33 in a reiteration of this TAP formation, to develop the linearly bonded oligomeric systems 35 (Scheme 10) [36].The TAP dimers (n = 2) with different substituents at the C2 position were reported by the Namba group, including a 2-unsubstituted TAP dimer.Unfortunately, the TAP trimers (n = 3) were, in general, too difficult to obtain due to decomposition during the elimination reactions (Table 8).An exception was the derivative with a tridecyl group at the C2 position.
The properties of TAP monomers, TAP dimers, and the TAP trimer were rather similar in the diluted solution in DCM, showing that introducing additional TAP rings had no drastic effect on the fluorescence characteristics [36].Interestingly, the linearly bonded TAP dimer 35 (n = 2, R = Ph) showed different fluorescence properties when varying the concentration, which suggested changes in the aggregation state.The phenyl-TAP-dimer showed mechanochromic fluorescence in the solid phase and a fluorescence wavelength redshift while going from the crystalline to the amorphous state upon grinding.Emission lifetimes were determined for the solid dimer 35 (n = 2, R = Ph) at 540 nm before (λem,max = 535 nm) and after grinding (λem,max = 590 nm), and were found to be 4.9 and 1.2, respectively.Notably, density functional theory (DFT) calculations verified the planar form of trimer-TAP (R = C13H27).

Acetylation and Nitrosation
Although 2-substituted TAPs 5 and 8 were sensitive to air, acetylation and nitrosation of these compounds could be carried out.The TAPs reacted at the C3 position, resulting in 3-acetyl and 3-nitroso derivatives in high yields (Scheme 9) [26].The successful electrophilic substitution reactions clearly demonstrated the electron rich nature of the TAP core.

Acetylation and Nitrosation
Although 2-substituted TAPs 5 and 8 were sensitive to air, acetylation and nitrosation of these compounds could be carried out.The TAPs reacted at the C3 position, resulting in 3-acetyl and 3-nitroso derivatives in high yields (Scheme 9) [26].The successful electrophilic substitution reactions clearly demonstrated the electron rich nature of the TAP core.

Linearly Bonded 1,3a,6a-Triazapentalene Dimers and Trimer
Starting from the azidotriflate 33 with protected alkyne function, a 2,5-disubstituted TAP with tert-butyldimethylsilyl ether (TBS) protecting group was synthesized via click reaction followed by cyclization.The azidotriflate 33 was prepared via a multistep synthesis [36].After removing the TBS group, the monoethyl-substituted triazapentalene 34 was applied as the starting material together with one more equivalent of 33 in a reiteration of this TAP formation, to develop the linearly bonded oligomeric systems 35 (Scheme 10) [36].The TAP dimers (n = 2) with different substituents at the C2 position were reported by the Namba group, including a 2-unsubstituted TAP dimer.Unfortunately, the TAP trimers (n = 3) were, in general, too difficult to obtain due to decomposition during the elimination reactions (Table 8).An exception was the derivative with a tridecyl group at the C2 position.
The properties of TAP monomers, TAP dimers, and the TAP trimer were rather similar in the diluted solution in DCM, showing that introducing additional TAP rings had no drastic effect on the fluorescence characteristics [36].Interestingly, the linearly bonded TAP dimer 35 (n = 2, R = Ph) showed different fluorescence properties when varying the concentration, which suggested changes in the aggregation state.The phenyl-TAP-dimer showed mechanochromic fluorescence in the solid phase and a fluorescence wavelength redshift while going from the crystalline to the amorphous state upon grinding.Emission lifetimes were determined for the solid dimer 35 (n = 2, R = Ph) at 540 nm before (λem,max = 535 nm) and after grinding (λem,max = 590 nm), and were found to be 4.9 and 1.2, respectively.Notably, density functional theory (DFT) calculations verified the planar form of trimer-TAP (R = C13H27).

Linearly Bonded 1,3a,6a-Triazapentalene Dimers and Trimer
Starting from the azidotriflate 33 with protected alkyne function, a 2,5-disubstituted TAP with tert-butyldimethylsilyl ether (TBS) protecting group was synthesized via click reaction followed by cyclization.The azidotriflate 33 was prepared via a multistep synthesis [36].After removing the TBS group, the monoethyl-substituted triazapentalene 34 was applied as the starting material together with one more equivalent of 33 in a reiteration of this TAP formation, to develop the linearly bonded oligomeric systems 35 (Scheme 10) [36].The TAP dimers (n = 2) with different substituents at the C2 position were reported by the Namba group, including a 2-unsubstituted TAP dimer.Unfortunately, the TAP trimers (n = 3) were, in general, too difficult to obtain due to decomposition during the elimination reactions (Table 8).An exception was the derivative with a tridecyl group at the C2 position.
The properties of TAP monomers, TAP dimers, and the TAP trimer were rather similar in the diluted solution in DCM, showing that introducing additional TAP rings had no drastic effect on the fluorescence characteristics [36].Interestingly, the linearly bonded TAP dimer 35 (n = 2, R = Ph) showed different fluorescence properties when varying the concentration, which suggested changes in the aggregation state.The phenyl-TAP-dimer showed mechanochromic fluorescence in the solid phase and a fluorescence wavelength redshift while going from the crystalline to the amorphous state upon grinding.Emission lifetimes were determined for the solid dimer 35 (n = 2, R = Ph) at 540 nm before (λ em,max = 535 nm) and after grinding (λ em,max = 590 nm), and were found to be 4.9 and 1.2, respectively.Notably, density functional theory (DFT) calculations verified the planar form of trimer-TAP (R = C 13 H 27 ).
Then, the TAP 12i was developed as a fluorescent reagent to label glycine ethyl ester and tripeptide Gly-Pro-Leu [28].By treating methyl ester TAP 12i with lithium hydroxide, a benzoic acid derivative was obtained that was directly converted into an activated Nhydroxysuccinimide (NHS) ester 38.As the purification from the DCC-derived urea was troublesome, instead, polymer-supported DCC was used and could be filtered off to give pure reactive ester 38.Subsequently, compound 38 was reacted with glycine ethyl ester and tripeptide Gly-Pro-Leu to obtain the labeled glycine 39 and tripeptide 40, respectively.Compounds 39 and 40 showed the same fluorescence maximum at 567 nm with 37% and 24% fluorescence quantum yields in DCM, respectively.The fluorescence measurements for these compounds in water demonstrated decreased Stokes shifts and quantum yields.Then, the TAP 12i was developed as a fluorescent reagent to label glycine ethyl ester and tripeptide Gly-Pro-Leu [28].By treating methyl ester TAP 12i with lithium hydroxide, a benzoic acid derivative was obtained that was directly converted into an activated Nhydroxysuccinimide (NHS) ester 38.As the purification from the DCC-derived urea was troublesome, instead, polymer-supported DCC was used and could be filtered off to give pure reactive ester 38.Subsequently, compound 38 was reacted with glycine ethyl ester and tripeptide Gly-Pro-Leu to obtain the labeled glycine 39 and tripeptide 40, respectively.Compounds 39 and 40 showed the same fluorescence maximum at 567 nm with 37% and 24% fluorescence quantum yields in DCM, respectively.The fluorescence measurements for these compounds in water demonstrated decreased Stokes shifts and quantum yields.The second application was based on compound 12e (Figure 2), which showed high fluorescence intensity in phosphate-buffered saline (PBS) and was applied as a fluorescent probe to observe cellular differentiation processes in various living cells [38].After treatment with a PBS solution of 12e, cytoplasmic and nuclear morphological changes during the differentiation processes were monitored by fluorescence microscopy.It was found that the fluorescence probe 12e had no toxicity, neither was there an effect on the cellular differentiation processes, and the probe could be easily washed away from the cells that can continue to culture for following studies.In a third application, TAP analogs of biphenyl-type kinesin spindle protein (KSP) inhibitors 41 and 42 (Figure 3) were prepared and investigated as bifunctional fluorescent probes [39].Both analogs showed inhibitory activity against KSP ATPase, although 42 was more potent (half maximal inhibitory concentration (IC50) was 6.8 µ M).Further microscopic studies were carried out with 42 in cultured cells in order to visualize the intracellular distribution.The partial colocalization of compound 42 with KSP, combined with its inhibitory activity, demonstrated the potency of the TAP fluorophore to be used as a probe for the visualization of bioactive substances and their targets.The second application was based on compound 12e (Figure 2), which showed high fluorescence intensity in phosphate-buffered saline (PBS) and was applied as a fluorescent probe to observe cellular differentiation processes in various living cells [38].After treatment with a PBS solution of 12e, cytoplasmic and nuclear morphological changes during the differentiation processes were monitored by fluorescence microscopy.It was found that the fluorescence probe 12e had no toxicity, neither was there an effect on the cellular differentiation processes, and the probe could be easily washed away from the cells that can continue to culture for following studies.Then, the TAP 12i was developed as a fluorescent reagent to label glycine ethyl ester and tripeptide Gly-Pro-Leu [28].By treating methyl ester TAP 12i with lithium hydroxide, a benzoic acid derivative was obtained that was directly converted into an activated Nhydroxysuccinimide (NHS) ester 38.As the purification from the DCC-derived urea was troublesome, instead, polymer-supported DCC was used and could be filtered off to give pure reactive ester 38.Subsequently, compound 38 was reacted with glycine ethyl ester and tripeptide Gly-Pro-Leu to obtain the labeled glycine 39 and tripeptide 40, respectively.Compounds 39 and 40 showed the same fluorescence maximum at 567 nm with 37% and 24% fluorescence quantum yields in DCM, respectively.The fluorescence measurements for these compounds in water demonstrated decreased Stokes shifts and quantum yields.The second application was based on compound 12e (Figure 2), which showed high fluorescence intensity in phosphate-buffered saline (PBS) and was applied as a fluorescent probe to observe differentiation processes in various living cells [38].After treatment with a PBS solution of 12e, cytoplasmic and nuclear morphological changes during the differentiation processes were monitored by fluorescence microscopy.It was found that the fluorescence probe 12e had no toxicity, neither was there an effect on the cellular differentiation processes, and the probe could be easily washed away from the cells that can continue to culture for following studies.In a third application, TAP analogs of biphenyl-type kinesin spindle protein (KSP) inhibitors 41 and 42 (Figure 3) were prepared and investigated as bifunctional fluorescent probes [39].Both analogs showed inhibitory activity against KSP ATPase, although 42 was more potent (half maximal inhibitory concentration (IC50) was 6.8 µ M).Further microscopic studies were carried out with 42 in cultured cells in order to visualize the intracellular distribution.The partial colocalization of compound 42 with KSP, combined with its inhibitory activity, demonstrated the potency of the TAP fluorophore to be used as a probe for the visualization of bioactive substances and their targets.In a third application, TAP analogs of biphenyl-type kinesin spindle protein (KSP) inhibitors 41 and 42 (Figure 3) were prepared and investigated as bifunctional fluorescent probes [39].Both analogs showed inhibitory activity against KSP ATPase, although 42 was more potent (half maximal inhibitory concentration (IC 50 ) was 6.8 µM).Further microscopic studies were carried out with 42 in cultured cells in order to visualize the intracellular distribution.The partial colocalization of compound 42 with KSP, combined with its inhibitory activity, demonstrated the potency of the TAP fluorophore to be used as a probe for the visualization of bioactive substances and their targets.Most recently, a compact vinyl ketone functionalized TAP 45 was cleverly designed by Namba et al. as a thiol-specific fluorescent labeling reagent [40].Starting from the previously reported 2-methoxycarbonyl-TAP 43, the electrophilic α,β-unsaturated ketone TAP 45 was prepared via a high-yielding multistep synthesis involving Weinreb amide 44 (Scheme 13).The 2-vinyl ketone-TAP 45 was then reacted with various thiols via thiol Michael additions to obtain compounds 46.Remarkably, the fluorescence intensity of 45 was turned off due to the conjugation of the vinyl ketone at the C2 position.After the addition of the thiol group, this conjugation was interrupted, and the fluorescence of compound 46 was turned on again while also exhibiting shorter emission wavelengths as compared to 45.A water-soluble R8 peptide was also successfully labeled in a phosphate buffer (pH 7).Although no fluorescence was observed in water, the labeled peptide became luminescent after uptake and localization in the hydrophobic regions of A549 cells.Advantageously, the vinyl ketone TAP did not cause any background fluorescence and was not found to be cytotoxic.Next, a captopril-TAP conjugate was prepared for drug imaging.Captopril is a cysteine derivative that inhibits angiotensin converting enzyme (ACE) and has been used for the treatment of hypertensive patients.The inhibitory activity and confocal laser microscope imaging studies in vascular endothelial cells demonstrated that the fluorophore had no impact on the activity of captopril and that the fluorophore could be used as a probe for mechanistic studies.In a final application, TAP derivative 51 was used as a fluorescent sensor for iron (Scheme 14) [41].Starting with a protected catechol-containing alkyne 48 and azide 10a, TAP 49 was obtained via the CuAAC reaction strategy.In order to increase the stability, an acetyl group was introduced into compound 49 at the C3 position through acylation.The acetylated compound 50 was further conjugated to serine trimer 47 by saponification and amide coupling.After deprotection with HCl, the TAP labeled enterobactin 51 was obtained.The influence of iron on the fluorescent properties of sensor 51 was studied with Fe(acac)3 as an Fe 3+ ion source at different concentrations.When increasing the amount of Fe 3+ in a DMSO solution of 51, the fluorescence intensity was decreased gradually, with complete disappearance at 1.2 equivalents of Fe(acac)3.The emission maximum did not change.In DMF and tert-butanol, a similar phenomenon was observed.Fourth-period metals also caused a clear decrease in fluorescence intensity, although no complete quenching was observed, even while adding 5.0 equivalents.Thus, 1,3a,6atriazapentalene-labeled enterobactin 51 was shown to be a selective and highly sensitive fluorescence-quenching sensor for iron (III).Most recently, a compact vinyl ketone functionalized TAP 45 was cleverly designed by Namba et al. as a thiol-specific fluorescent labeling reagent [40].Starting from the previously reported 2-methoxycarbonyl-TAP 43, the electrophilic α,β-unsaturated ketone TAP 45 was prepared via a high-yielding multistep synthesis involving Weinreb amide 44 (Scheme 13).The 2-vinyl ketone-TAP 45 was then reacted with various thiols via thiol Michael additions to obtain compounds 46.Remarkably, the fluorescence intensity of 45 was turned off due to the conjugation of the vinyl ketone at the C2 position.After addition of the thiol group, this conjugation was interrupted, and the fluorescence of compound 46 was turned on again while also exhibiting shorter emission wavelengths as compared to 45.A water-soluble R8 peptide was also successfully labeled in a phosphate buffer (pH 7).Although no fluorescence was observed in water, the labeled peptide became luminescent after uptake and localization in the hydrophobic regions of A549 cells.Advantageously, the vinyl ketone TAP did not cause any background fluorescence and was not found to be cytotoxic.Next, a captopril-TAP conjugate was prepared for drug imaging.Captopril is a cysteine derivative that inhibits angiotensin converting enzyme (ACE) and has been used for the treatment of hypertensive patients.The inhibitory activity and confocal laser microscope imaging studies in vascular endothelial cells demonstrated that the fluorophore had no impact on the activity of captopril and that the fluorophore could be used as a probe for mechanistic studies.Most recently, a compact vinyl ketone functionalized TAP 45 was cleverly designed by Namba et al. as a thiol-specific fluorescent labeling reagent [40].Starting from the previously reported 2-methoxycarbonyl-TAP 43, the electrophilic α,β-unsaturated ketone TAP 45 was prepared via a high-yielding multistep synthesis involving Weinreb amide 44 (Scheme 13).The 2-vinyl ketone-TAP 45 was then reacted with various thiols via thiol Michael additions to obtain compounds 46.Remarkably, the fluorescence intensity of 45 was turned off due to the conjugation of the vinyl ketone at the C2 position.After the addition of the thiol group, this conjugation was interrupted, and the fluorescence of compound 46 was turned on again while also exhibiting shorter emission wavelengths as compared to 45.A water-soluble R8 peptide was also successfully labeled in a phosphate buffer (pH 7).Although no fluorescence was observed in water, the labeled peptide became luminescent after uptake and localization in the hydrophobic regions of A549 cells.Advantageously, the vinyl ketone TAP did not cause any background fluorescence and was not found to be cytotoxic.Next, a captopril-TAP conjugate was prepared for drug imaging.Captopril is a cysteine derivative that inhibits angiotensin converting enzyme (ACE) and has been used for the treatment of hypertensive patients.The inhibitory activity and confocal laser microscope imaging studies in vascular endothelial cells demonstrated that the fluorophore had no impact on the activity of captopril and that the fluorophore could be used as a probe for mechanistic studies.In a final application, TAP derivative 51 was used as a fluorescent sensor for iron (Scheme 14) [41].Starting with a protected catechol-containing alkyne 48 and azide 10a, TAP 49 was obtained via the CuAAC reaction strategy.In order to increase the stability, an acetyl group was introduced into compound 49 at the C3 position through acylation.The acetylated compound 50 was further conjugated to serine trimer 47 by saponification and amide coupling.After deprotection with HCl, the TAP labeled enterobactin 51 was obtained.The influence of iron on the fluorescent properties of sensor 51 was studied with Fe(acac)3 as an Fe 3+ ion source at different concentrations.When increasing the amount of Fe 3+ in a DMSO solution of 51, the fluorescence intensity was decreased gradually, with complete disappearance at 1.2 equivalents of Fe(acac)3.The emission maximum did not change.In DMF and tert-butanol, a similar phenomenon was observed.Fourth-period metals also caused a clear decrease in fluorescence intensity, although no complete quenching was observed, even while adding 5.0 equivalents.Thus, 1,3a,6atriazapentalene-labeled enterobactin 51 was shown to be a selective and highly sensitive fluorescence-quenching sensor for iron (III).In a final application, TAP derivative 51 was used as a fluorescent sensor for iron (Scheme 14) [41].Starting with a protected catechol-containing alkyne 48 and azide 10a, TAP 49 was obtained via the CuAAC reaction strategy.In order to increase the stability, an acetyl group was introduced into compound 49 at the C3 position through acylation.The acetylated compound 50 was further conjugated to serine trimer 47 by saponification and amide coupling.After deprotection with HCl, the TAP labeled enterobactin 51 was obtained.The influence of iron on the fluorescent properties of sensor 51 was studied with Fe(acac) 3 as an Fe 3+ ion source at different concentrations.When increasing the amount of Fe 3+ in a DMSO solution of 51, the fluorescence intensity was decreased gradually, with complete disappearance at 1.2 equivalents of Fe(acac) 3 .The emission maximum did not change.In DMF and tert-butanol, a similar phenomenon was observed.Fourth-period metals also caused a clear decrease in fluorescence intensity, although no complete quenching was observed, even while adding 5.0 equivalents.Thus, 1,3a,6a-triazapentalene-labeled enterobactin 51 was shown to be a selective and highly sensitive fluorescence-quenching sensor for iron (III).

Conclusions
In this mini review, we have discussed the different synthetic methodologies of bicyclic 1,3a,6a-triazapentalenes.An alternative to the earlier synthesis from pyrazoles and aminating reagents was provided by the CuAAC-based strategy, which could be used to synthesize a wide scope of 2-substituted TAPs.The gold-catalyzed cyclization pathway afforded excellent yields of highly functionalized TAPs with electron withdrawing functional groups at the C3 position.Unfortunately, the starting materials for these methods often need to be prepared via a multistep synthesis.The triazolization-mediated synthesis provided access to 2-unsubstituted TAPs from readily available starting materials.Therefore, this was complementary to the previous strategies.
As a result of the profound studies by Namba et al., the substituent effects on the properties of TAP are known and could allow one to design the fluorophores according to the requirements of a particular application.For example, the stability of the TAP core could at first be ensured by introducing an electron withdrawing group at the C3 position, while the fluorescence wavelength could be adjusted by variation of the substituent at the C2 position.Further adjustments of the properties could be made with the substituent at

Conclusions
In this mini review, we have discussed the different synthetic methodologies of bicyclic 1,3a,6a-triazapentalenes.An alternative to the earlier synthesis from pyrazoles and aminating reagents was provided by the CuAAC-based strategy, which could be used to synthesize a wide scope of 2-substituted TAPs.The gold-catalyzed cyclization pathway afforded excellent yields of highly functionalized TAPs with electron withdrawing functional groups at the C3 position.Unfortunately, the starting materials for these methods often need to be prepared via a multistep synthesis.The triazolization-mediated synthesis provided access to 2-unsubstituted TAPs from readily available starting materials.Therefore, this was complementary to the previous strategies.
As a result of the profound studies by Namba et al., the substituent effects on the properties of TAP are known and could allow one to design the fluorophores according to the requirements of a particular application.For example, the stability of the TAP core could at first be ensured by introducing an electron withdrawing group at the C3 position, while the fluorescence wavelength could be adjusted by variation of the substituent at the C2 position.Further adjustments of the properties could be made with the substituent at the C4, C5 or C6 position.For instance, the extinction coefficient and therefore brightness of TAPs could be increased by introducing a substituent at the C4 position.For the TAP compounds that require high quantum yields, often it is a good idea to introduce a substituent at the C5 or C6 position.
Applications of TAPs were mainly focused on live-cell fluorescence imaging, in particular drug imaging, although an application as iron chemosensor was also reported.The small size of the TAP core is often mentioned as an advantage compared to other fluorescent probes.Up to this moment, reports about TAP probes and sensors have been limited to 2-substituted TAPs, which are obtained via the CuAAC method.Problems that often occur and still need to be solved are poor solubility and weak fluorescence intensity of the TAP probes in water.
We are only at the start of the applications of this new and compact fluorophore TAP.Hopefully, this review will stimulate further investigations.

Scheme 3 .
Scheme 3. The synthesis of 2-substituted TAPs 12 and the parent TAP 12b.

Scheme 12 .
Scheme 12. Synthesis of TAP-labeled labeled glycine 39 and tripeptide 40 and properties in DCM. a Measured in water.Su = succinimide.

Scheme 12 .
Scheme 12. Synthesis of TAP-labeled labeled glycine 39 and tripeptide 40 and properties in DCM. a Measured in water.Su = succinimide.

Scheme 12 .
Scheme 12. Synthesis of TAP-labeled labeled glycine 39 and tripeptide 40 and properties in DCM. a Measured in water.Su = succinimide.

Table 1 .
Fluorescence properties and reaction yields of selected 2-substituted TAPs 12c-g in DCM.

Table 1 .
Fluorescence properties and reaction yields of selected 2-substituted TAPs 12c-g in DCM.

Table 1 .
Fluorescence properties and reaction yields of selected 2-substituted TAPs 12c-g in DCM.

Table 1 .
Fluorescence properties and reaction yields of selected 2-substituted TAPs 12c-g in DCM.

Table 1 .
Fluorescence properties and reaction yields of selected 2-substituted TAPs 12c-g in DCM.

Table 1 .
Fluorescence properties and reaction yields of selected 2-substituted TAPs 12c-g in DCM.

Table 1 .
Fluorescence properties and reaction yields of selected 2-substituted TAPs 12c-g in DCM.

Table 1 .
Fluorescence properties and reaction yields of selected 2-substituted TAPs 12c-g in DCM.

Table 1 .
Fluorescence properties and reaction yields of selected 2-substituted TAPs 12c-g in DCM.

Table 1 .
Fluorescence properties and reaction yields of selected 2-substituted TAPs 12c-g in DCM.

Table 1 .
Fluorescence properties and reaction yields of selected 2-substituted TAPs 12c-g in DCM.

Table 4 .
Fluorescence properties and reaction yields of 2-substituted 4-methyl-TAPs 14c-h in DCM.Reaction yield of 4-unsubstituted analog.b Absorption maximum of corresponding 4-unsubstituted analog.c Fluorescenc maximum of corresponding 4-unsubstituted analog.d Quantum yield of corresponding 4-unsubstituted analog. a
a Absorption maximum of corresponding 4-unsubstituted analog.b Fluorescence maximum of corresponding 4-unsubst tuted analog.c Quantum yield of corresponding 4-unsubstituted analog.d Extinction coefficient value

Table 4 .
Fluorescence properties and reaction yields of 2-substituted 4-methyl-TAPs 14c-h in DCM.Reaction yield of 4-unsubstituted analog.b Absorption maximum of corresponding 4-unsubstituted analog.c Fluorescence maximum of corresponding 4-unsubstituted analog.d Quantum yield of corresponding 4-unsubstituted analog. a

Table 4 .
Fluorescence properties and reaction yields of 2-substituted 4-methyl-TAPs 14c-h in DCM.Reaction yield of 4-unsubstituted analog.b Absorption maximum of corresponding 4-unsubstituted analog.c Fluorescence maximum of corresponding 4-unsubstituted analog.d Quantum yield of corresponding 4-unsubstituted analog. a
a Absorption maximum of corresponding 4-unsubstituted analog.b Fluorescence maximum of corresponding 4-unsubstituted analog.c Quantum yield of corresponding 4-unsubstituted analog.d Extinction coefficient value of

Table 4 .
Fluorescence properties and reaction yields of 2-substituted 4-methyl-TAPs 14c-h in DCM.Reaction yield of 4-unsubstituted analog.b Absorption maximum of corresponding 4-unsubstituted analog.c Fluorescence maximum of corresponding 4-unsubstituted analog.d Quantum yield of corresponding 4-unsubstituted analog. a
a Absorption maximum of corresponding 4-unsubstituted analog.b Fluorescence maximum of corresponding 4-unsubstituted analog.c Quantum yield of corresponding 4-unsubstituted analog.d Extinction coefficient value of

Table 4 .
Fluorescence properties and reaction yields of 2-substituted 4-methyl-TAPs 14c-h in DCM.Reaction yield of 4-unsubstituted analog.b Absorption maximum of corresponding 4-unsubstituted analog.c Fluorescence maximum of corresponding 4-unsubstituted analog.d Quantum yield of corresponding 4-unsubstituted analog. a
a Absorption maximum of corresponding 4-unsubstituted analog.b Fluorescence maximum of corresponding 4-unsubstituted analog.c Quantum yield of corresponding 4-unsubstituted analog.d Extinction coefficient value of

Table 4 .
Fluorescence properties and reaction yields of 2-substituted 4-methyl-TAPs 14c-h in DCM.Reaction yield of 4-unsubstituted analog.b Absorption maximum of corresponding 4-unsubstituted analog.c Fluorescence maximum of corresponding 4-unsubstituted analog.d Quantum yield of corresponding 4-unsubstituted analog. a
a Absorption maximum of corresponding 4-unsubstituted analog.b Fluorescence maximum of corresponding 4-unsubstituted analog.c Quantum yield of corresponding 4-unsubstituted analog.d Extinction coefficient value of Reaction yield of 4-unsubstituted analog.b Absorption maximum of corresponding 4-unsubstituted analog.c Fluorescence maximum of corresponding 4-unsubstituted analog.d Quantum yield of corresponding 4-unsubstituted analog. a

Table 4 .
Fluorescence properties and reaction yields of 2-substituted 4-methyl-TAPs 14c-h in DCM.Reaction yield of 4-unsubstituted analog.b Absorption maximum of corresponding 4-unsubstituted analog.c Fluorescence maximum of corresponding 4-unsubstituted analog.d Quantum yield of corresponding 4-unsubstituted analog. a
a Absorption maximum of corresponding 4-unsubstituted analog.b Fluorescence maximum of corresponding 4-unsubsti tuted analog.c Quantum yield of corresponding 4-unsubstituted analog.d Extinction coefficient value of corresponding 4 unsubstituted analog.
a Absorption maximum of corresponding 4-unsubstituted analog.b Fluorescence maximum of corresponding 4-unsubstituted analog.c Quantum yield of corresponding 4-unsubstituted analog.d Extinction coefficient value of corresponding 4unsubstituted analog.
a Absorption maximum of corresponding 4-unsubstituted analog.b Fluorescence maximum of corresponding 4-unsubstituted analog.c Quantum yield of corresponding 4-unsubstituted analog.d Extinction coefficient value of corresponding 4unsubstituted analog.
a Absorption maximum of corresponding 4-unsubstituted analog.b Fluorescence maximum of corresponding 4-unsubstituted analog.c Quantum yield of corresponding 4-unsubstituted analog.d Extinction coefficient value of corresponding 4unsubstituted analog.
a Absorption maximum of corresponding 4-unsubstituted analog.b Fluorescence maximum of corresponding 4-unsubstituted analog.c Quantum yield of corresponding 4-unsubstituted analog.d Extinction coefficient value of corresponding 4unsubstituted analog.

Table 4 .
Fluorescence properties and reaction yields of 2-substituted 4-methyl-TAPs 14c-h in DCM.Reaction yield of 4-unsubstituted analog.b Absorption maximum of corresponding 4-unsubstituted analog.c Fluorescence maximum of corresponding 4-unsubstituted analog.d Quantum yield of corresponding 4-unsubstituted analog. a
a Absorption maximum of corresponding 4-unsubstituted analog.b Fluorescence maximum of corresponding 4-unsubstituted analog.c Quantum yield of corresponding 4-unsubstituted analog.d Extinction coefficient value of corresponding 4unsubstituted analog.
a Reaction yield of 4-unsubstituted analog.b Absorption maximum of corresponding 4-unsubstituted analog.c Fluorescence maximum of corresponding 4-unsubstituted analog.d Quantum yield of corresponding 4-unsubstituted analog.
a Absorption maximum of corresponding 4-unsubstituted analog.b Fluorescence maximum of corresponding 4-unsubstituted analog.c Quantum yield of corresponding 4-unsubstituted analog.d Extinction coefficient value of corresponding 4-unsubstituted analog.

Table 6 .
Fluorescence properties and reaction yields of selected 2-substituted 6-methyl-TAPs in DCM.

Table 7 .
Fluorescent properties and reaction yields of 3-substituted TAPs 31 in DCM.

Table 7 .
Fluorescent properties and reaction yields of 3-substituted TAPs 31 in DCM.

Table 7 .
Fluorescent properties and reaction yields of 3-substituted TAPs 31 in DCM.

Table 7 .
Fluorescent properties and reaction yields of 3-substituted TAPs 31 in DCM.

Table 7 .
Fluorescent properties and reaction yields of 3-substituted TAPs 31 in DCM.

Table 7 .
Fluorescent properties and reaction yields of 3-substituted TAPs 31 in DCM.
a No data available.