Synthesis of Novel Key Chromophoric Intermediates via C-C Coupling Reactions

: The fundamentals of Pd-catalyzed Csp 2 − Csp 2 Miyaura borylation, Suzuki cross-coupling, and Stille cross-coupling reactions for a variety of borylated precursors based on phenothiazine (PTZ), phenoxazine (POZ), carbazole (Cz), and quinoxaline (QX) units have been explored. Three palladium-based catalysts were chosen for this study: Pd(PPh 3 ) 4 , Pd(PPh 3 ) 2 Cl 2 , and Pd(dppf)Cl 2 , applying different reaction conditions. Around 16 desired chromophores were successfully designed and synthesized using C-C cross-coupling reactions in moderate to excellent yields, including PTZ, POZ, and Cz units coupled with QX, indolinium iodide, thienyl, phenyl, or triphenylamine moieties. Addition-ally, PTZ, POZ, and Cz have been employed in synthesizing various pinacol boronate ester derivatives in good to moderate yields. Interestingly, Pd(dppf)Cl 2 was found to be the best catalyst for borylation, and C-C cross-coupling reactions occurred in as little as 30 min, with an excellent yield exceeding 98%. Pd(PPh 3 ) 4 and Pd(PPh 3 ) 2 Cl 2 catalyzed the reaction to obtain the desired products in moderate to good yields after a long time (20–24 h). On the other hand, the Suzuki-Miyaura cross-coupling between N -(2-methyl)hexyl carbazole pinacol boronate ester derivative 10c and three halogenated quinoxaline derivatives—4-(3-(5-bromothiophen-2-yl)quinoxalin-2-yl)benzaldehyde ( 27 ), 4-(5-(3-(5-bromothiophen-2-yl)quinoxalin-2-yl)thiophen-2-yl)benzaldehyde ( 30 ), and 4-(3-chloroquinoxalin-2-yl)benzaldehyde ( 25 ) catalyzed by Pd(PPh 3 ) 4 —afforded three carbazole-quinoxaline chromophores ( 28 , 30 , and 31 , respectively) in 2–3 h, with good to excellent yields reaching 86%. The electron-deﬁcient QX couplers proved to be coupled efﬁciently using the Stille coupling reaction, which involves the coupling between electron-rich orgaostannane and electron-deﬁcient halide. The synthesized precursors and desired chromophores were characterized by FTIR, 1 H-NMR, 13 C-NMR, and HRMS.

Quinoxaline is considered an electron-deficient moiety thanks to the two electronwithdrawing imine (C=N) groups in the pyrazine ring. Subsequently, it was selected to be a good coupler in C-C coupling reactions. Wisely, three quinoxaline derivatives (21,24,26) have been synthesized utilizing the Suzuki cross-coupling reaction and Stille coupling reaction (Scheme 3) using Pd(PPh 3 ) 4 and Pd(PPh 3 ) 2 Cl 2 , respectively. The substituted dibromoquinoxaline coupler 20 was successfully synthesized in four steps, starting from the benzothiadiazole compound 17 obtained from the reaction of o-phenylenediamine with thionyl chloride in the presence of pyridine. Then, a di-bromination reaction with N-bromosuccimide followed by a sulfur extrusion reaction using the good reducing reagent sodium borohydride afforded 18 and 19, respectively. Forming 2,3-diphenylquinoxaline moiety was accomplished through the condensation of compound 19 with benzil in an acidic medium. The Stille coupling reaction was performed on coupler 20 for the decoration of chromophore 21 with two thiophene rings. This coupling reaction utilized 2-(tributylstannyl)thiophene in the presence of Pd(PPh 3 ) 2 Cl 2 , which gives an excellent yield of 85%, owing to the electron deficiency of the quinoxaline central core. On the other hand, the reaction between o-phenylenediamine and oxalic acid afforded quinoxalinedione 22, which underwent a double chlorination reaction using POCl 3

in DMF to
Catalysts 2022, 12, 1292 6 of 24 obtain 2,3-dichloroquinoxaline 23. Then, again, the Stille coupling reaction was performed between coupler 23 and 2-(tributylstannyl)thiophene to obtain 2.3-dithienylquinoxaline 24. The two Cl in compound 23 were exploited for the synthesis of chromophore 26 in two steps: first, Suzuki cross-coupling with 4-formylphenylboronic acid using Pd(PPh 3 ) 4 to obtain compound 25, which then coupled with 2-(tributylstannyl)thiophene through a Stille coupling reaction to afford 26 in a moderate yield (66%). acidic medium. The Stille coupling reaction was performed on coupler 20 for the decoration of chromophore 21 with two thiophene rings. This coupling reaction utilized 2-(tributylstannyl)thiophene in the presence of Pd(PPh3)2Cl2, which gives an excellent yield of 85%, owing to the electron deficiency of the quinoxaline central core. On the other hand, the reaction between o-phenylenediamine and oxalic acid afforded quinoxalinedione 22, which underwent a double chlorination reaction using POCl3 in DMF to obtain 2,3-dichloroquinoxaline 23. Then, again, the Stille coupling reaction was performed between coupler 23 and 2-(tributylstannyl)thiophene to obtain 2.3-dithienylquinoxaline 24. The two Cl in compound 23 were exploited for the synthesis of chromophore 26 in two steps: first, Suzuki cross-coupling with 4-formylphenylboronic acid using Pd(PPh3)4 to obtain compound 25, which then coupled with 2-(tributylstannyl)thiophene through a Stille coupling reaction to afford 26 in a moderate yield (66%).
Additionally, the synthesized quinoxaline chromophores 24 and 26 and the carbazole-BPin derivative 10c were used in the synthesis of the three carbazole-quinoxaline chromophores 28, 31, and 32, as shown in Scheme 4. Initially, the thiophene ring in both 24 and 26 were brominated at position 5 using the formal bromination conditions of NBS in DMF to afford two couplers, 27 and 29. Coupler 30 was obtained from the Suzuki cross-coupling reaction between coupler 29 and 4-formylphenylboronic acid. Finally, cou-plers 27, 30, and 25 were coupled with the carbazole-BPin derivative 10c for the synthesis of 28, 31, and 32 in good yields. The structures of all of these compounds were confirmed by the spectral data of IR, 1 H-NMR, 13 C-NMR, DEPT-135, and HRMS (see supplementary data; Figures S1-S83).
To discuss the different conditions of the Miyaura borylation, Suzuki cross-coupling reaction, and Stille coupling reactions, summaries of our work in the field were illustrated in Tables 1-4. The Miyaura borylation reaction has been accomplished for the synthesis of PTZ, POZ, and Cz heteroarylboronates (4, 6a-c, and 10a-c) under the following conditions: Pd(PPh 3 ) 2 Cl 2 or Pd(dppf)Cl 2 as catalysts and sources for palladium, potassium acetate as a weak base, toluene or dioxane as reaction media, and refluxing from 90 to 110 • C for 12-24 h under N 2 or Ar (Table 1). Obviously, the use of Pd(PPh 3 ) 2 Cl 2 in the borylation of PTZ-, POZ-, and Cz-based boronates linked to imidazolyl (5) or p-tolyl (10a-c) moieties afforded the corresponding boronates in moderate yields of Pd-catalyzed borylation reaction (60-70%), even by using two different linking groups of bulky triphenyl imidazole and simple p-tolyl units and two different molar ratios (substrate:catalyst:base of 50:1:125 for imidazolyl derivative 5 and 20:1:60 for p-tolyl derivatives 10a-c). Fortunately, the use of Pd(dppf)Cl 2 in the borylation reaction catalysis of brominated PTZ, POZ, and Cz compounds was successfully accomplished in the synthesis of PTZ, POZ, and Cz heteroarylboronates bearing an aldehyde group 6a-c in excellent yields (94-98%), applying a molar ratio of 20:1:60 but with the same long time of 24 h. It is noteworthy that the yield obtained was much higher for the boronate esters 6a-c compared with 5 and 10a-c. This result is mainly attributed to the electronic structure of the substrate. As can be seen, the formyl substrates are much more deactivated due to the formyl group compared with the imidazolyl moiety. This attribution is manifested using the p-tolyl analogues 10a-c, as these compounds are electronically activated; thus, the yield was lower than that of 6a-c.  5 24 h under N2 or Ar (Table 1). Obviously, the use of Pd(PPh3)2Cl2 in the borylation of PTZ-, POZ-, and Cz-based boronates linked to imidazolyl (5) or p-tolyl (10a-c) moieties afforded the corresponding boronates in moderate yields of Pd-catalyzed borylation reaction (60-70%), even by using two different linking groups of bulky triphenyl imidazole and simple p-tolyl units and two different molar ratios (substrate:catalyst:base of 50:1:125 for imidazolyl derivative 5 and 20:1:60 for p-tolyl derivatives 10a-c). Fortunately, the use of Pd(dppf)Cl2 in the borylation reaction catalysis of brominated PTZ, POZ, and Cz compounds was successfully accomplished in the synthesis of PTZ, POZ, and Cz heteroarylboronates bearing an aldehyde group 6a-c in excellent yields (94-98%), applying a molar ratio of 20:1:60 but with the same long time of 24 h. It is noteworthy that the yield obtained was much higher for the boronate esters 6a-c compared with 5 and 10a-c. This result is mainly attributed to the electronic structure of the substrate. As can be seen, the formyl substrates are much more deactivated due to the formyl group compared with the imidazolyl moiety. This attribution is manifested using the p-tolyl analogues 10a-c, as these compounds are electronically activated; thus, the yield was lower than that of 6a-c. By applying Suzuki cross-coupling conditions in reacting brominated electron-donors PTZ, POZ, and Cz with 4-tolylboronic acid in the presence of Pd(PPh3)4 and potassium carbonate in toluene, compounds 9a-c were obtained in moderate yields (76-50%) during a reaction period of 24 h. Lower yields (37-20%) were obtained for compounds 25 and 30 from Suzuki coupling between the electron-deficient halogenated QX couplers 23 and 29 and 4-formylphenyl boronic acid using the same conditions of Pd(PPh3)4 and K2CO3 and a reaction time of 20-24 h. The low yields may be attributed to the acidity of compounds 23 and 29, which makes this compound susceptible to hydrolysis, together with the orthodicholoro steric factor. Furthermore, boronic acids easily undergo side reactions such as oxidation, protodeboronation, or palladium-catalyzed homocoupling during Suzuki coupling reactions [56]. Moreover, in anhydrous conditions, boronic acids tend to be in equilibrium with a trimeric anhydride (boroxine), and this process is not straightforward. Thus, an excess of boronic acids is required in the Suzuki cross-coupling reaction [17].  (Table 1). Obviously, the use of Pd(PPh3)2Cl2 in the borylation of PTZ-, POZ-, and Cz-based boronates linked to imidazolyl (5) or p-tolyl (10a-c) moieties afforded the corresponding boronates in moderate yields of Pd-catalyzed borylation reaction (60-70%), even by using two different linking groups of bulky triphenyl imidazole and simple p-tolyl units and two different molar ratios (substrate:catalyst:base of 50:1:125 for imidazolyl derivative 5 and 20:1:60 for p-tolyl derivatives 10a-c). Fortunately, the use of Pd(dppf)Cl2 in the borylation reaction catalysis of brominated PTZ, POZ, and Cz compounds was successfully accomplished in the synthesis of PTZ, POZ, and Cz heteroarylboronates bearing an aldehyde group 6a-c in excellent yields (94-98%), applying a molar ratio of 20:1:60 but with the same long time of 24 h. It is noteworthy that the yield obtained was much higher for the boronate esters 6a-c compared with 5 and 10a-c. This result is mainly attributed to the electronic structure of the substrate. As can be seen, the formyl substrates are much more deactivated due to the formyl group compared with the imidazolyl moiety. This attribution is manifested using the p-tolyl analogues 10a-c, as these compounds are electronically activated; thus, the yield was lower than that of 6a-c. By applying Suzuki cross-coupling conditions in reacting brominated electron-donors PTZ, POZ, and Cz with 4-tolylboronic acid in the presence of Pd(PPh3)4 and potassium carbonate in toluene, compounds 9a-c were obtained in moderate yields (76-50%) during a reaction period of 24 h. Lower yields (37-20%) were obtained for compounds 25 and 30 from Suzuki coupling between the electron-deficient halogenated QX couplers 23 and 29 and 4-formylphenyl boronic acid using the same conditions of Pd(PPh3)4 and K2CO3 and a reaction time of 20-24 h. The low yields may be attributed to the acidity of compounds 23 and 29, which makes this compound susceptible to hydrolysis, together with the orthodicholoro steric factor. Furthermore, boronic acids easily undergo side reactions such as oxidation, protodeboronation, or palladium-catalyzed homocoupling during Suzuki coupling reactions [56]. Moreover, in anhydrous conditions, boronic acids tend to be in equilibrium with a trimeric anhydride (boroxine), and this process is not straightforward. Thus, an excess of boronic acids is required in the Suzuki cross-coupling reaction [17].  (Table 1). Obviously, the use of Pd(PPh3)2Cl2 in the borylation of PTZ-, POZ-, and Cz-based boronates linked to imidazolyl (5) or p-tolyl (10a-c) moieties afforded the corresponding boronates in moderate yields of Pd-catalyzed borylation reaction (60-70%), even by using two different linking groups of bulky triphenyl imidazole and simple p-tolyl units and two different molar ratios (substrate:catalyst:base of 50:1:125 for imidazolyl derivative 5 and 20:1:60 for p-tolyl derivatives 10a-c). Fortunately, the use of Pd(dppf)Cl2 in the borylation reaction catalysis of brominated PTZ, POZ, and Cz compounds was successfully accomplished in the synthesis of PTZ, POZ, and Cz heteroarylboronates bearing an aldehyde group 6a-c in excellent yields (94-98%), applying a molar ratio of 20:1:60 but with the same long time of 24 h. It is noteworthy that the yield obtained was much higher for the boronate esters 6a-c compared with 5 and 10a-c. This result is mainly attributed to the electronic structure of the substrate. As can be seen, the formyl substrates are much more deactivated due to the formyl group compared with the imidazolyl moiety. This attribution is manifested using the p-tolyl analogues 10a-c, as these compounds are electronically activated; thus, the yield was lower than that of 6a-c. By applying Suzuki cross-coupling conditions in reacting brominated electron-donors PTZ, POZ, and Cz with 4-tolylboronic acid in the presence of Pd(PPh3)4 and potassium carbonate in toluene, compounds 9a-c were obtained in moderate yields (76-50%) during a reaction period of 24 h. Lower yields (37-20%) were obtained for compounds 25 and 30 from Suzuki coupling between the electron-deficient halogenated QX couplers 23 and 29 and 4-formylphenyl boronic acid using the same conditions of Pd(PPh3)4 and K2CO3 and a reaction time of 20-24 h. The low yields may be attributed to the acidity of compounds 23 and 29, which makes this compound susceptible to hydrolysis, together with the orthodicholoro steric factor. Furthermore, boronic acids easily undergo side reactions such as oxidation, protodeboronation, or palladium-catalyzed homocoupling during Suzuki coupling reactions [56]. Moreover, in anhydrous conditions, boronic acids tend to be in equilibrium with a trimeric anhydride (boroxine), and this process is not straightforward. Thus, an excess of boronic acids is required in the Suzuki cross-coupling reaction [17]. By applying Suzuki cross-coupling conditions in reacting brominated electron-donors PTZ, POZ, and Cz with 4-tolylboronic acid in the presence of Pd(PPh 3 ) 4 and potassium carbonate in toluene, compounds 9a-c were obtained in moderate yields (76-50%) during a reaction period of 24 h. Lower yields (37-20%) were obtained for compounds 25 and 30 from Suzuki coupling between the electron-deficient halogenated QX couplers 23 and 29 and 4-formylphenyl boronic acid using the same conditions of Pd(PPh 3 ) 4 and K 2 CO 3 and a reaction time of 20-24 h. The low yields may be attributed to the acidity of compounds 23 and 29, which makes this compound susceptible to hydrolysis, together with the orthodicholoro steric factor. Furthermore, boronic acids easily undergo side reactions such as oxidation, protodeboronation, or palladium-catalyzed homocoupling during Suzuki coupling reactions [56]. Moreover, in anhydrous conditions, boronic acids tend to be in equilibrium with a trimeric anhydride (boroxine), and this process is not straightforward. Thus, an excess of boronic acids is required in the Suzuki cross-coupling reaction [17].
Interestingly, the electron-deficient QX couplers proved to be coupled efficiently using the Stille coupling reaction, which involves the coupling between electron-rich orgaostannane and electron-deficient halide, without the use of the base. This result confirms that the basic medium is unsuitable for such electron-deficient molecules, owing to their acidity. Thus, di-brominated and di-and mono-chlorinated QX couplers were subjected to Stille coupling conditions in the presence of tributyl stannyl thiophene catalyzed by Pd(PPh 3 ) 2 Cl 2 .
Among the three halogenated couplers demonstrated in Table 3, the most electron-deficient QX derivative, 2,3-dichloroquioxaline 23, afforded chromophore 24 in an excellent yield Catalysts 2022, 12, 1292 9 of 24 (98%) in only one hour. The di-brominated QX coupler 20, which is less electron-deficient due to the conjugation with two phenyl groups, gave a good yield (85%) of product 21 in 2 h. Coupler 25, which has a QX unit linked to the 4-formylphenyl moiety, afforded a moderate yield (66%) of product 26, which may be attributed to a steric factor. The overall results of QX-based couplers confirm the suitability of the Stille coupling condition compared with the Suzuki one.  Interestingly, the electron-deficient QX couplers proved to be coupled efficiently using the Stille coupling reaction, which involves the coupling between electron-rich orgaostannane and electron-deficient halide, without the use of the base. This result confirms that the basic medium is unsuitable for such electron-deficient molecules, owing to their acidity. Thus, di-brominated and di-and mono-chlorinated QX couplers were subjected to Stille coupling conditions in the presence of tributyl stannyl thiophene catalyzed by Pd(PPh3)2Cl2. Among the three halogenated couplers demonstrated in Table 3, the most electron-deficient QX derivative, 2,3-dichloroquioxaline 23, afforded chromophore 24 in an excellent yield (98%) in only one hour. The di-brominated QX coupler 20, which is less electron-deficient due to the conjugation with two phenyl groups, gave a good yield (85%) of product 21 in 2 h. Coupler 25, which has a QX unit linked to the 4-formylphenyl moiety, afforded a moderate yield (66%) of product 26, which may be attributed to a steric factor. The overall results of QX-based couplers confirm the suitability of the Stille coupling condition compared with the Suzuki one.  Interestingly, the electron-deficient QX couplers proved to be coupled efficiently using the Stille coupling reaction, which involves the coupling between electron-rich orgaostannane and electron-deficient halide, without the use of the base. This result confirms that the basic medium is unsuitable for such electron-deficient molecules, owing to their acidity. Thus, di-brominated and di-and mono-chlorinated QX couplers were subjected to Stille coupling conditions in the presence of tributyl stannyl thiophene catalyzed by Pd(PPh3)2Cl2. Among the three halogenated couplers demonstrated in Table 3, the most electron-deficient QX derivative, 2,3-dichloroquioxaline 23, afforded chromophore 24 in an excellent yield (98%) in only one hour. The di-brominated QX coupler 20, which is less electron-deficient due to the conjugation with two phenyl groups, gave a good yield (85%) of product 21 in 2 h. Coupler 25, which has a QX unit linked to the 4-formylphenyl moiety, afforded a moderate yield (66%) of product 26, which may be attributed to a steric factor. The overall results of QX-based couplers confirm the suitability of the Stille coupling condition compared with the Suzuki one.  Interestingly, the electron-deficient QX couplers proved to be coupled efficiently using the Stille coupling reaction, which involves the coupling between electron-rich orgaostannane and electron-deficient halide, without the use of the base. This result confirms that the basic medium is unsuitable for such electron-deficient molecules, owing to their acidity. Thus, di-brominated and di-and mono-chlorinated QX couplers were subjected to Stille coupling conditions in the presence of tributyl stannyl thiophene catalyzed by Pd(PPh3)2Cl2. Among the three halogenated couplers demonstrated in Table 3, the most electron-deficient QX derivative, 2,3-dichloroquioxaline 23, afforded chromophore 24 in an excellent yield (98%) in only one hour. The di-brominated QX coupler 20, which is less electron-deficient due to the conjugation with two phenyl groups, gave a good yield (85%) of product 21 in 2 h. Coupler 25, which has a QX unit linked to the 4-formylphenyl moiety, afforded a moderate yield (66%) of product 26, which may be attributed to a steric factor. The overall results of QX-based couplers confirm the suitability of the Stille coupling condition compared with the Suzuki one.  Interestingly, the electron-deficient QX couplers proved to be coupled efficiently using the Stille coupling reaction, which involves the coupling between electron-rich orgaostannane and electron-deficient halide, without the use of the base. This result confirms that the basic medium is unsuitable for such electron-deficient molecules, owing to their acidity. Thus, di-brominated and di-and mono-chlorinated QX couplers were subjected to Stille coupling conditions in the presence of tributyl stannyl thiophene catalyzed by Pd(PPh3)2Cl2. Among the three halogenated couplers demonstrated in Table 3, the most electron-deficient QX derivative, 2,3-dichloroquioxaline 23, afforded chromophore 24 in an excellent yield (98%) in only one hour. The di-brominated QX coupler 20, which is less electron-deficient due to the conjugation with two phenyl groups, gave a good yield (85%) of product 21 in 2 h. Coupler 25, which has a QX unit linked to the 4-formylphenyl moiety, afforded a moderate yield (66%) of product 26, which may be attributed to a steric factor. The overall results of QX-based couplers confirm the suitability of the Stille coupling condition compared with the Suzuki one.  Interestingly, the electron-deficient QX couplers proved to be coupled efficiently using the Stille coupling reaction, which involves the coupling between electron-rich orgaostannane and electron-deficient halide, without the use of the base. This result confirms that the basic medium is unsuitable for such electron-deficient molecules, owing to their acidity. Thus, di-brominated and di-and mono-chlorinated QX couplers were subjected to Stille coupling conditions in the presence of tributyl stannyl thiophene catalyzed by Pd(PPh3)2Cl2. Among the three halogenated couplers demonstrated in Table 3, the most electron-deficient QX derivative, 2,3-dichloroquioxaline 23, afforded chromophore 24 in an excellent yield (98%) in only one hour. The di-brominated QX coupler 20, which is less electron-deficient due to the conjugation with two phenyl groups, gave a good yield (85%) of product 21 in 2 h. Coupler 25, which has a QX unit linked to the 4-formylphenyl moiety, afforded a moderate yield (66%) of product 26, which may be attributed to a steric factor. The overall results of QX-based couplers confirm the suitability of the Stille coupling condition compared with the Suzuki one.  Interestingly, the electron-deficient QX couplers proved to be coupled efficiently using the Stille coupling reaction, which involves the coupling between electron-rich orgaostannane and electron-deficient halide, without the use of the base. This result confirms that the basic medium is unsuitable for such electron-deficient molecules, owing to their acidity. Thus, di-brominated and di-and mono-chlorinated QX couplers were subjected to Stille coupling conditions in the presence of tributyl stannyl thiophene catalyzed by Pd(PPh3)2Cl2. Among the three halogenated couplers demonstrated in Table 3, the most electron-deficient QX derivative, 2,3-dichloroquioxaline 23, afforded chromophore 24 in an excellent yield (98%) in only one hour. The di-brominated QX coupler 20, which is less electron-deficient due to the conjugation with two phenyl groups, gave a good yield (85%) of product 21 in 2 h. Coupler 25, which has a QX unit linked to the 4-formylphenyl moiety, afforded a moderate yield (66%) of product 26, which may be attributed to a steric factor. The overall results of QX-based couplers confirm the suitability of the Stille coupling condition compared with the Suzuki one.  Interestingly, the electron-deficient QX couplers proved to be coupled efficiently using the Stille coupling reaction, which involves the coupling between electron-rich orgaostannane and electron-deficient halide, without the use of the base. This result confirms that the basic medium is unsuitable for such electron-deficient molecules, owing to their acidity. Thus, di-brominated and di-and mono-chlorinated QX couplers were subjected to Stille coupling conditions in the presence of tributyl stannyl thiophene catalyzed by Pd(PPh3)2Cl2. Among the three halogenated couplers demonstrated in Table 3, the most electron-deficient QX derivative, 2,3-dichloroquioxaline 23, afforded chromophore 24 in an excellent yield (98%) in only one hour. The di-brominated QX coupler 20, which is less electron-deficient due to the conjugation with two phenyl groups, gave a good yield (85%) of product 21 in 2 h. Coupler 25, which has a QX unit linked to the 4-formylphenyl moiety, afforded a moderate yield (66%) of product 26, which may be attributed to a steric factor. The overall results of QX-based couplers confirm the suitability of the Stille coupling condition compared with the Suzuki one.  Interestingly, the electron-deficient QX couplers proved to be coupled efficiently using the Stille coupling reaction, which involves the coupling between electron-rich orgaostannane and electron-deficient halide, without the use of the base. This result confirms that the basic medium is unsuitable for such electron-deficient molecules, owing to their acidity. Thus, di-brominated and di-and mono-chlorinated QX couplers were subjected to Stille coupling conditions in the presence of tributyl stannyl thiophene catalyzed by Pd(PPh3)2Cl2. Among the three halogenated couplers demonstrated in Table 3, the most electron-deficient QX derivative, 2,3-dichloroquioxaline 23, afforded chromophore 24 in an excellent yield (98%) in only one hour. The di-brominated QX coupler 20, which is less electron-deficient due to the conjugation with two phenyl groups, gave a good yield (85%) of product 21 in 2 h. Coupler 25, which has a QX unit linked to the 4-formylphenyl moiety, afforded a moderate yield (66%) of product 26, which may be attributed to a steric factor. The overall results of QX-based couplers confirm the suitability of the Stille coupling condition compared with the Suzuki one. The conditions of the Suzuki cross-coupling reactions between the synthesized PTZ, POZ, and Cz boronates and the halogenated indolinium, triphenylamine, and quinoxaline couplers are summarized in Table 4. In terms of catalysis, Pd(dppf)Cl2 efficiently catalyzed the reaction to afford the desired chromophores 14 and 15a-c in excellent yields ranging from 90% to 98%. The phenoxazine-based indolinium chromophores 14 and 15b took a longer reaction time (24 h) in contrast to the phenothiazine and carbazole counterparts,  mine coupler, in which the Br-C bond is very much activated with the electron-donor character of the amine moiety that would hamper the oxidative coupling when compared with the other cationic coupler. It is worth noting that QX-based couplers could afford a higher yield when boronate ester is used (Table 4) instead of boronic acid ( Table 2). This result reflects the usefulness of Miyaura boronate ester over boronic acid for the C-C cross-coupling reaction, because boronic acid acts as a proton donor during the coupling condition, which could lower the yield of the reaction. mine coupler, in which the Br-C bond is very much activated with the electron-donor character of the amine moiety that would hamper the oxidative coupling when compared with the other cationic coupler. It is worth noting that QX-based couplers could afford a higher yield when boronate ester is used (Table 4) instead of boronic acid ( Table 2). This result reflects the usefulness of Miyaura boronate ester over boronic acid for the C-C cross-coupling reaction, because boronic acid acts as a proton donor during the coupling condition, which could lower the yield of the reaction. mine coupler, in which the Br-C bond is very much activated with the electron-donor character of the amine moiety that would hamper the oxidative coupling when compared with the other cationic coupler. It is worth noting that QX-based couplers could afford a higher yield when boronate ester is used (Table 4) instead of boronic acid ( Table 2). This result reflects the usefulness of Miyaura boronate ester over boronic acid for the C-C cross-coupling reaction, because boronic acid acts as a proton donor during the coupling condition, which could lower the yield of the reaction. mine coupler, in which the Br-C bond is very much activated with the electron-donor character of the amine moiety that would hamper the oxidative coupling when compared with the other cationic coupler. It is worth noting that QX-based couplers could afford a higher yield when boronate ester is used (Table 4) instead of boronic acid ( Table 2). This result reflects the usefulness of Miyaura boronate ester over boronic acid for the C-C cross-coupling reaction, because boronic acid acts as a proton donor during the coupling condition, which could lower the yield of the reaction. mine coupler, in which the Br-C bond is very much activated with the electron-donor character of the amine moiety that would hamper the oxidative coupling when compared with the other cationic coupler. It is worth noting that QX-based couplers could afford a higher yield when boronate ester is used (Table 4) instead of boronic acid ( Table 2). This result reflects the usefulness of Miyaura boronate ester over boronic acid for the C-C cross-coupling reaction, because boronic acid acts as a proton donor during the coupling condition, which could lower the yield of the reaction. mine coupler, in which the Br-C bond is very much activated with the electron-donor character of the amine moiety that would hamper the oxidative coupling when compared with the other cationic coupler. It is worth noting that QX-based couplers could afford a higher yield when boronate ester is used (Table 4) instead of boronic acid ( Table 2). This result reflects the usefulness of Miyaura boronate ester over boronic acid for the C-C cross-coupling reaction, because boronic acid acts as a proton donor during the coupling condition, which could lower the yield of the reaction. triphenylamine chromophore 16, the low yield of 49% was attributed to the triphenyla-mine coupler, in which the Br-C bond is very much activated with the electron-donor character of the amine moiety that would hamper the oxidative coupling when compared with the other cationic coupler. It is worth noting that QX-based couplers could afford a higher yield when boronate ester is used (Table 4) instead of boronic acid ( Table 2). This result reflects the usefulness of Miyaura boronate ester over boronic acid for the C-C cross-coupling reaction, because boronic acid acts as a proton donor during the coupling condition, which could lower the yield of the reaction. quinoxaline chromophores 28, 31, and 32, which were catalyzed by Pd(PPh3)4 and gave good yields of 69-86% in a comparatively short time (2-3 h). In the case of phenothiazinetriphenylamine chromophore 16, the low yield of 49% was attributed to the triphenylamine coupler, in which the Br-C bond is very much activated with the electron-donor character of the amine moiety that would hamper the oxidative coupling when compared with the other cationic coupler. It is worth noting that QX-based couplers could afford a higher yield when boronate ester is used (Table 4) instead of boronic acid (Table 2). This result reflects the usefulness of Miyaura boronate ester over boronic acid for the C-C cross-coupling reaction, because boronic acid acts as a proton donor during the coupling condition, which could lower the yield of the reaction. triphenylamine chromophore 16, the low yield of 49% was attributed to the triphenylamine coupler, in which the Br-C bond is very much activated with the electron-donor character of the amine moiety that would hamper the oxidative coupling when compared with the other cationic coupler. It is worth noting that QX-based couplers could afford a higher yield when boronate ester is used (Table 4) instead of boronic acid (Table 2). This result reflects the usefulness of Miyaura boronate ester over boronic acid for the C-C cross-coupling reaction, because boronic acid acts as a proton donor during the coupling condition, which could lower the yield of the reaction.

Materials and Instrumentation
Solvents produced from Sigma, Aldrich, and Fisher were used without purification. All of the used chemicals were of the analytical grade and were used in the synthesis without more purification. The separations of compounds were performed by column chromatography on silica gel (0.063-0.2 mm). The purity of the products was checked by thin layer chromatography (TLC) using an aluminum silica gel F254, and the spot was detected by iodine and/or UV light absorption. NMR spectra were recorded in DMSO-d6 or CDCl3 on Bruker Avance 600 MHz or 850 MHz spectrometers for 1 H-NMR and on a 213 MHz spectrometer for 13 C-NMR, using the deuterated solvent signal as the internal standard. Chemical shifts (δ) are given in ppm, and coupling constants are given in Hz. The Fourier transform infrared (FTIR) spectra were carried out on a Thermo Scientific Nicolet iS10 FTIR spectrometer. The Thermo Scientific Orbitrap ID-X Tribrid mass spectrometer was used to obtain high-resolution mass spectra (HRMS).

Synthesis of 10-octyl-10H-phenothiazine (1a)
Sodium hydroxide (2.0 g, 35.7 mmol) was added to a solution of 10H-phenothiazine (2.4 g, 11.9 mmol), 1-bromooctane (3.5 g, 17.9 mmol), and potassium iodide (catalytic) in 50 mL dimethyl formamide (DMF). The reaction mixture was stirred for 5 h at room temperature, and then 200 mL of water was added. The crude product was extracted with chloroform (3 × 50 mL), and the organic layer was washed with saturated ammonium The conditions of the Suzuki cross-coupling reactions between the synthesized PTZ, POZ, and Cz boronates and the halogenated indolinium, triphenylamine, and quinoxaline couplers are summarized in Table 4. In terms of catalysis, Pd(dppf)Cl 2 efficiently catalyzed the reaction to afford the desired chromophores 14 and 15a-c in excellent yields ranging from 90% to 98%. The phenoxazine-based indolinium chromophores 14 and 15b took a longer reaction time (24 h) in contrast to the phenothiazine and carbazole counterparts, which were obtained in half an hour. This is in contrast to the synthesis of the carbazolequinoxaline chromophores 28, 31, and 32, which were catalyzed by Pd(PPh 3 ) 4 and gave good yields of 69-86% in a comparatively short time (2-3 h). In the case of phenothiazinetriphenylamine chromophore 16, the low yield of 49% was attributed to the triphenylamine coupler, in which the Br-C bond is very much activated with the electron-donor character of the amine moiety that would hamper the oxidative coupling when compared with the other cationic coupler. It is worth noting that QX-based couplers could afford a higher yield when boronate ester is used (Table 4) instead of boronic acid (Table 2). This result reflects the usefulness of Miyaura boronate ester over boronic acid for the C-C cross-coupling reaction, because boronic acid acts as a proton donor during the coupling condition, which could lower the yield of the reaction.

Materials and Instrumentation
Solvents produced from Sigma, Aldrich, and Fisher were used without purification. All of the used chemicals were of the analytical grade and were used in the synthesis without more purification. The separations of compounds were performed by column chromatography on silica gel (0.063-0.2 mm). The purity of the products was checked by thin layer chromatography (TLC) using an aluminum silica gel F254, and the spot was detected by iodine and/or UV light absorption. NMR spectra were recorded in DMSO-d 6 or CDCl 3 on Bruker Avance 600 MHz or 850 MHz spectrometers for 1 H-NMR and on a 213 MHz spectrometer for 13 C-NMR, using the deuterated solvent signal as the internal standard. Chemical shifts (δ) are given in ppm, and coupling constants are given in Hz. The Fourier transform infrared (FTIR) spectra were carried out on a Thermo Scientific Nicolet iS10 FTIR spectrometer. The Thermo Scientific Orbitrap ID-X Tribrid mass spectrometer was used to obtain high-resolution mass spectra (HRMS).

Synthesis of 10-octyl-10H-phenothiazine (1a)
Sodium hydroxide (2.0 g, 35.7 mmol) was added to a solution of 10H-phenothiazine (2.4 g, 11.9 mmol), 1-bromooctane (3.5 g, 17.9 mmol), and potassium iodide (catalytic) in 50 mL dimethyl formamide (DMF). The reaction mixture was stirred for 5 h at room temperature, and then 200 mL of water was added. The crude product was extracted with chloroform (3 × 50 mL), and the organic layer was washed with saturated ammonium chloride aqueous solution and then water. The organic layer was dried over anhydrous sodium sulfate. After removing the solvent, the residue was purified by column chromatography on silica gel by using n-Hexane as an eluent to obtain 3.4 g (90%) of compound 1a as a colorless oil. 1

4-(3-Chloroquinoxalin-2-yl)benzaldehyde (25)
Compound 23 (0.5 g, 2.5 mmol, 1.0 eq), 4-formylphenylboronic acid (0.6 g, 3.8 mmol, 1.5 eq), K 2 CO 3 (0.3 g, 2.5 mmol, 1.0 eq), and Pd(PPh 3 ) 4 (0.1 g, 0.1 mmol, 0.03 eq) were mixed in mixture solvent of dry toluene/MeOH 5:1 (60 mL) under an argon atmosphere and a drying system of CaCl 2 with stirring at ambient temperature. Then, the reaction mixture was heated for 20 h at 80 • C and monitored by TLC. After the reaction was complete, the solvent was removed under vacuum and extracted by distilled water and EA (30 mL × 4-5 times). The combined organic extract was washed with brine and dried over anhydrous Na 2 SO 4 . Then, the solvent was removed at reduced pressure to afford the crude product and was purified by silica gel column chromatography, using PE/EA (9:1) as an eluent, to remove the residue of the start. This was followed by increasing the polarity of the eluent gradually until 8:2 to obtain the desired compound 25 as a white powder (0.3 g, 37%) (m.p. 167 • C). 1  To a mixture of compound 25 (0.2 g, 0.7 mmol, 1.0 eq) and tributyl(thiophen-2yl)stannane (0.6 g, 1.5 mmol, 2.0 eq) in dry DMF (30 mL), Pd(PPh 3 ) 2 Cl 2 (0.03 g, 0.04 mmol, 0.05 eq) was added under an argon atmosphere. It was then refluxed for 2 h at 110 • C while monitoring the reaction by TLC. After the reaction was complete, the temperature was lowered to get the mixture to room temperature, followed by the addition of water to stop the reaction. Following CHCl 3 extraction of the product (30 mL × 4-5 times), it was washed with brine and dried over anhydrous Na 2 SO 4 . Then, the solvent was removed under reduced pressure to obtain the crude product and was purified by column chromatography on silica gel, using PE/EA (9:1) as an eluent, to obtain 26 as a yellow powder (0.2 g, 66%) (m.p. 157 • C). 1