Condensation of Diacetyl with Alkyl Amines: Synthesis and Reactivity of p-Iminobenzoquinones and p-Diiminobenzoquinones

Condensation reactions between diacetyl and α-branched primary alkylamines under mild and neutral conditions provided a mixture of 2,5-dimethylbenzoquinone(alkylimines), 2,5-dimethylbenzoquinone(bis-alkyldiimines), and N,N′-dialkyl-2,5-dimethylbenzene-1,4-diamines, which were efficiently separated as pure products by column chromatography. Both 2,5-dimethylbenzoquinone(alkylimines) and 2,5-dimethylbenzoquinone(bis-alkyldiimines) underwent an interchange of the alkylimino group when treated with anilines, followed by reductive aromatization, to provide diarylamines and 1,4-dianilinobenzenes, respectively. Evaluation was also made of the reactivity and selectivity of these compounds in the presence of anilines, thiophenols and alkylhalides.

Recently, as a result of the synthesis of novel 2-imidazolidinone-base outer-ring exo-heterocyclic dienes 5 [27], we found that a base-assisted condensation/cyclization cascade reaction of monoimino diacetyl derivatives 3 and isocyanates in the presence of a dehydrating agent provided the desired dienes in high yields (Scheme 1). The monoimino diacetyl derivatives 3 were efficiently prepared by reacting 1a with anilines 2 under neutral or Lewis acid catalysis conditions. However, derivatives 3 could not be prepared by using primary alkylamines. Only a limited number of old reports have described this kind of reaction, which exclusively yield brownish resins and oils, except for the thermochromic amber-yellow colored crystalline 2,5-dimethylbenzoquinone-bis-cyclohexyldiimine (8b) afforded by cyclohexylamine (6b) [33] (see below). All our attempts to purify these compounds by column chromatography over silica gel furnished decomposition resins.
Considering the limited scope of this reaction and the instability of the products, it is comprehensible that, to our best knowledge, no additional studies on this process have been reported. In spite of the drawbacks of an apparently disappointing and uninspiring reaction, we saw promise. With further investigation, in the mixture found of products 7-9, the proportion depended on the reaction conditions. Therefore, we herein describe the efforts to gain insight into the limits and scope of this interesting reaction between diacetyl (1a) and alkylamines 6.
Molecules 2015, 20, page-page 2 Recently, as a result of the synthesis of novel 2-imidazolidinone-base outer-ring exo-heterocyclic dienes 5 [27], we found that a base-assisted condensation/cyclization cascade reaction of monoimino diacetyl derivatives 3 and isocyanates in the presence of a dehydrating agent provided the desired dienes in high yields (Scheme 1). The monoimino diacetyl derivatives 3 were efficiently prepared by reacting 1a with anilines 2 under neutral or Lewis acid catalysis conditions. However, derivatives 3 could not be prepared by using primary alkylamines. Only a limited number of old reports have described this kind of reaction, which exclusively yield brownish resins and oils, except for the thermochromic amber-yellow colored crystalline 2,5-dimethylbenzoquinone-bis-cyclohexyldiimine (8b) afforded by cyclohexylamine (6b) [33] (see below). All our attempts to purify these compounds by column chromatography over silica gel furnished decomposition resins.
Considering the limited scope of this reaction and the instability of the products, it is comprehensible that, to our best knowledge, no additional studies on this process have been reported. In spite of the drawbacks of an apparently disappointing and uninspiring reaction, we saw promise. With further investigation, in the mixture found of products 7-9, the proportion depended on the reaction conditions. Therefore, we herein describe the efforts to gain insight into the limits and scope of this interesting reaction between diacetyl (1a) and alkylamines 6. Scheme 1. Reaction of diacetyl (1a) with anilines 2 and alkylamines 6. Table 1 summarizes the reaction conditions of the process between 1a and isopropylamine (6a). It appears that both the presence and proportion of two or three products depends not only on the number of mol equivalents of the amine, but also on the concentration of the reaction mixture (entries [1][2][3][4]. Among the several solvents tested, methanol turned out to be the most efficient, though propanol could provide similar results albeit in lower yields (entry 5). The process yielded a larger proportion of iminoquinones 7a and 8a as well as their greater conversion when using twice the amount of 6a and at high dilution (entry 4).

Condensation of Diacetyl (1a) with Amines 6
Interestingly, when hydroquinone was added to quench the probable formation of radical species, 1,4-diaminobenzene compound 9a was the lone product (entry 6). This result suggests that the aromatization was readily performed under mild reductive conditions (see below). These three products could be separated as solids by flash column chromatography over 10% triethylamine pre-treated silica gel. However, if the crude mixture remained in the column for a long time, the yields decreased and many red and brown resin products were formed. Particular caution should be taken with products 7 and 8, keeping them under refrigeration. Despite their instability, they can be handled at room temperature for further transformations. Scheme 1. Reaction of diacetyl (1a) with anilines 2 and alkylamines 6.

Results and Discussion
2.1. Condensation of Diacetyl (1a) with Amines 6 Table 1 summarizes the reaction conditions of the process between 1a and isopropylamine (6a). It appears that both the presence and proportion of two or three products depends not only on the number of mol equivalents of the amine, but also on the concentration of the reaction mixture (entries [1][2][3][4]. Among the several solvents tested, methanol turned out to be the most efficient, though propanol could provide similar results albeit in lower yields (entry 5). The process yielded a larger proportion of iminoquinones 7a and 8a as well as their greater conversion when using twice the amount of 6a and at high dilution (entry 4).
Interestingly, when hydroquinone was added to quench the probable formation of radical species, 1,4-diaminobenzene compound 9a was the lone product (entry 6). This result suggests that the aromatization was readily performed under mild reductive conditions (see below). These three products could be separated as solids by flash column chromatography over 10% triethylamine pre-treated silica gel. However, if the crude mixture remained in the column for a long time, the yields decreased and many red and brown resin products were formed. Particular caution should be 20720 Molecules 2015, 20, taken with products 7 and 8, keeping them under refrigeration. Despite their instability, they can be handled at room temperature for further transformations.

Entry
i-PrNH2 (6a) (mol equiv.) Analogous results were obtained when other α-branched primary amines were used (Table 2). Thus, cyclohexylamine (6b) reacted with 1a under similar conditions to those used for 6a to yield the expected three products 7b/8b/9b (entry 1). Nevertheless, for (S)-methylbenzylamine (6c), the iminoquinone 7c was not observed (entry 2). Also tested were primary n-alkylamines, such as n-propylamine (6e) and benzylamine (6f), obtaining a complex mixture of products (Table 2, entries 4-5). n-Butylamine (6d) afforded the corresponding 1,4-diaminobenzene 9d in low yield (18%). These results could not be improved even when modifying the solvent, temperature and reaction times. Therefore, it appears that this kind of processes (leading to the formation of iminoquinones 7-9) did not occur when primary amines were used, with the exception of n-butylamine that led to 9d in low yield.

Functionalization of Iminoquinone 7a. Synthesis of Diarylamines and Polysubstituted Benzene Rings
Iminoquinone 7a underwent substitution at the isopropylimino moiety when it reacted with anilines 2a-c to furnish iminoquinones 10a-c in moderate to good yields (Scheme 2). Diverse studies have used the latter kind of molecules as intermediates for oxidative couplings of anilines with phenols to form dyes [34,35]. Iminoquinones have more recently resulted from oxidative bioconjugated couplings of anilines [36,37]. Interestingly, only the first of the two possible (E) and (Z) geometric isomers was obtained presently, which may be due to the destabilizing steric interactions generated Entry i-PrNH 2 (6a) (mol equiv.) Analogous results were obtained when other α-branched primary amines were used (Table 2). Thus, cyclohexylamine (6b) reacted with 1a under similar conditions to those used for 6a to yield the expected three products 7b/8b/9b (entry 1). Nevertheless, for (S)-methylbenzylamine (6c), the iminoquinone 7c was not observed (entry 2).

Entry
i-PrNH2 (6a) (mol equiv.) Analogous results were obtained when other α-branched primary amines were used (Table 2). Thus, cyclohexylamine (6b) reacted with 1a under similar conditions to those used for 6a to yield the expected three products 7b/8b/9b (entry 1). Nevertheless, for (S)-methylbenzylamine (6c), the iminoquinone 7c was not observed (entry 2). Also tested were primary n-alkylamines, such as n-propylamine (6e) and benzylamine (6f), obtaining a complex mixture of products (Table 2, entries 4-5). n-Butylamine (6d) afforded the corresponding 1,4-diaminobenzene 9d in low yield (18%). These results could not be improved even when modifying the solvent, temperature and reaction times. Therefore, it appears that this kind of processes (leading to the formation of iminoquinones 7-9) did not occur when primary amines were used, with the exception of n-butylamine that led to 9d in low yield.

Functionalization of Iminoquinone 7a. Synthesis of Diarylamines and Polysubstituted Benzene Rings
Iminoquinone 7a underwent substitution at the isopropylimino moiety when it reacted with anilines 2a-c to furnish iminoquinones 10a-c in moderate to good yields (Scheme 2). Diverse studies have used the latter kind of molecules as intermediates for oxidative couplings of anilines with phenols to form dyes [34,35]. Iminoquinones have more recently resulted from oxidative bioconjugated couplings of anilines [36,37]. Interestingly, only the first of the two possible (E) and (Z) geometric isomers was obtained presently, which may be due to the destabilizing steric interactions generated Also tested were primary n-alkylamines, such as n-propylamine (6e) and benzylamine (6f), obtaining a complex mixture of products (Table 2, entries 4-5). n-Butylamine (6d) afforded the corresponding 1,4-diaminobenzene 9d in low yield (18%). These results could not be improved even when modifying the solvent, temperature and reaction times. Therefore, it appears that this kind of processes (leading to the formation of iminoquinones 7-9) did not occur when primary amines were used, with the exception of n-butylamine that led to 9d in low yield.

Functionalization of Iminoquinone 7a. Synthesis of Diarylamines and Polysubstituted Benzene Rings
Iminoquinone 7a underwent substitution at the isopropylimino moiety when it reacted with anilines 2a-c to furnish iminoquinones 10a-c in moderate to good yields (Scheme 2). Diverse studies have used the latter kind of molecules as intermediates for oxidative couplings of anilines with phenols to form dyes [34,35]. Iminoquinones have more recently resulted from oxidative bioconjugated couplings of anilines [36,37]. Interestingly, only the first of the two possible (E) and (Z) geometric isomers was obtained presently, which may be due to the destabilizing steric interactions generated in the (Z) isomer. The geometry was established by NOE experiments and single crystal X-ray diffraction of 8a ( Figure 1).
Consequently, we have investigated the conversion of iminoquinones 10a-c into polysubstituted diarylamines 11-18. Aromatization of iminoquinones 10a-c under mild treatment with sodium hydrosulfite led to diarylamines 11a-c in high yields (Scheme 2). The latter compounds were reacted with different alkyl halides in order to obtain the O-or N-alkyl derivatives 12a-d. Accordingly, benzyl bromide (1.0 mol equiv.) afforded the O-benzylated diarylamine 12a in high yield, while the reaction of 11a-b with methyl bromoacetate led to phenoxyacetates 12b-c, respectively, in good yields. When compound 11b was submitted to methylation with methyl iodine (2.0 mol equiv.), the O,N-dimethyl diarylamine 12d was yielded.

Scheme 2. Conversion of 7a into diarylamines 11-14.
A further functionalization of iminoquinone 10b was successfully accomplished by adding a series of thiols 13a-d, furnishing the series of diarylamines 14a-d in modest to good yields (Scheme 2). Thus, the aminophenolic ring became a pentasubstituted benzene ring. Although we expected that the most polarized enone-quinoid system of 10b would be the most reactive site for the nucleophilic Diarylamines have become important synthetic targets as fine chemicals and precursors of a variety of N-containing pharmacological and natural products [38][39][40], such as carbazoles and ellipticines [41][42][43][44][45]. Due to the importance of diarylamines, a great number of synthetic approaches have been designed for their preparation [46][47][48]. One of the shortest and most efficient methods is through the Buchwald-Hartwig reaction, which consists of a Pd-catalyzed cross-coupling of aryl halides and anilines [49][50][51][52][53][54]. Another is the Ullmann reaction via a Cu-catalyzed coupling of similar substrates [55,56].
Consequently, we have investigated the conversion of iminoquinones 10a-c into polysubstituted diarylamines 11-18. Aromatization of iminoquinones 10a-c under mild treatment with sodium hydrosulfite led to diarylamines 11a-c in high yields (Scheme 2). The latter compounds were reacted with different alkyl halides in order to obtain the Oor N-alkyl derivatives 12a-d. Accordingly, benzyl bromide (1.0 mol equiv.) afforded the O-benzylated diarylamine 12a in high yield, while the reaction of 11a-b with methyl bromoacetate led to phenoxyacetates 12b-c, respectively, in good yields. When compound 11b was submitted to methylation with methyl iodine (2.0 mol equiv.), the O,N-dimethyl diarylamine 12d was yielded.
Consequently, we have investigated the conversion of iminoquinones 10a-c into polysubstituted diarylamines 11-18. Aromatization of iminoquinones 10a-c under mild treatment with sodium hydrosulfite led to diarylamines 11a-c in high yields (Scheme 2). The latter compounds were reacted with different alkyl halides in order to obtain the O-or N-alkyl derivatives 12a-d. Accordingly, benzyl bromide (1.0 mol equiv.) afforded the O-benzylated diarylamine 12a in high yield, while the reaction of 11a-b with methyl bromoacetate led to phenoxyacetates 12b-c, respectively, in good yields. When compound 11b was submitted to methylation with methyl iodine (2.0 mol equiv.), the O,N-dimethyl diarylamine 12d was yielded.

Scheme 2. Conversion of 7a into diarylamines 11-14.
A further functionalization of iminoquinone 10b was successfully accomplished by adding a series of thiols 13a-d, furnishing the series of diarylamines 14a-d in modest to good yields (Scheme 2). Thus, the aminophenolic ring became a pentasubstituted benzene ring. Although we expected that the most polarized enone-quinoid system of 10b would be the most reactive site for the nucleophilic A further functionalization of iminoquinone 10b was successfully accomplished by adding a series of thiols 13a-d, furnishing the series of diarylamines 14a-d in modest to good yields (Scheme 2). Thus, the aminophenolic ring became a pentasubstituted benzene ring. Although we expected that the most polarized enone-quinoid system of 10b would be the most reactive site for the nucleophilic conjugated addition, the imino-quinoid moiety was the site at which the conjugated addition of thiols 13a-d took place, followed by spontaneous aromatization. Although both alkyl-and arylthiols reacted efficiently, the latter furnished the desired products in higher yields.
This preference may be the result of favorable electronic interactions between both species. Presumably, thiophenol (a soft nucleophile) is selectively added to the conjugated imino-quinoid moiety, which should be softer than the enone moiety. The latter is highly polarized by the oxygen atom, mainly due to its electronegativity, which turns the enone system into a harder electrophile [57]. Although the results of similar studies support the importance of these electronic effects to explain this chemoselectivity [58], steric hindrance cannot be ruled out. The conjugated attack of the bulky thiophenol to the enone may be restrained by the presence of the vicinal anilino group, whose (E) configuration places the aryl ring on the same side of the unsubstituted enone carbon. In addition, this aryl ring adopts a slightly non-coplanar conformation with respect to the plane formed by the imino-quinoid ring [59,60], which may enhance such steric repulsion.
The structure of phenols 14a-d was unambiguously established by 2D and NOE NMR experiments. The 2D HMBC showed a clear three-bond correlation between the protons of the CH 3 -C6 methyl group, both carbon atoms attached to the OH group (C-1), and the lone benzene proton (C-5). A similar correlation was observed between the protons of the CH 3 -C3 methyl group and both carbon atoms at the base of the thioether and anilino groups (C-2 and C-4). Due to the close chemical shifts of the aromatic proton signals (selectively impeding irradiation as well as the ability to observe the corresponding signal enhancements), the NOE experiments were carried out with the O-allyl derivative of 14c (see compound 17c).
Taking into account the feasible nucleophilic conjugated addition of thiols 13 to 10b, anilines 2 were considered as potential nucleophiles. Therefore, the most nucleophilic p-anisidine (2b) was added to 10b, but no addition product was detected. In spite of this result, a trial was carried out starting from 7a and in the presence of an excess (2.0 mol equiv.) of 2b, followed by the reduction treatment, resulting in a mixture of 11b as the major product and the desired adduct 15 as the minor one (Scheme 3). Due to the difficulty of purifying the latter, the benzyl diarylamine 16 was generated (with compound 12a as the major product) in a one-pot procedure without the isolation of 15. It is worth mentioning that these reactions followed the same chemoselective addition pathway to the imino quinoid system as the thiols 13a-d. The low yields of products 15 and 16, and the fact that other less activated anilines were unable to give the double addition, may be explained by the lower nucleophilicity of anilines with respect to thiols. Also unsuccessful was the conjugated addition of soft nucleophiles, such as dimethyl malonate or nitromethane carbanions to iminoquinone 7a or anilinoquinone 10b, that led to the recovery of the starting materials.
Molecules 2015, 20, page-page conjugated addition, the imino-quinoid moiety was the site at which the conjugated addition of thiols 13a-d took place, followed by spontaneous aromatization. Although both alkyl-and arylthiols reacted efficiently, the latter furnished the desired products in higher yields.
This preference may be the result of favorable electronic interactions between both species. Presumably, thiophenol (a soft nucleophile) is selectively added to the conjugated imino-quinoid moiety, which should be softer than the enone moiety. The latter is highly polarized by the oxygen atom, mainly due to its electronegativity, which turns the enone system into a harder electrophile [57]. Although the results of similar studies support the importance of these electronic effects to explain this chemoselectivity [58], steric hindrance cannot be ruled out. The conjugated attack of the bulky thiophenol to the enone may be restrained by the presence of the vicinal anilino group, whose (E) configuration places the aryl ring on the same side of the unsubstituted enone carbon. In addition, this aryl ring adopts a slightly non-coplanar conformation with respect to the plane formed by the imino-quinoid ring [59,60], which may enhance such steric repulsion.
The structure of phenols 14a-d was unambiguously established by 2D and NOE NMR experiments. The 2D HMBC showed a clear three-bond correlation between the protons of the CH3-C6 methyl group, both carbon atoms attached to the OH group (C-1), and the lone benzene proton (C-5). A similar correlation was observed between the protons of the CH3-C3 methyl group and both carbon atoms at the base of the thioether and anilino groups (C-2 and C-4). Due to the close chemical shifts of the aromatic proton signals (selectively impeding irradiation as well as the ability to observe the corresponding signal enhancements), the NOE experiments were carried out with the O-allyl derivative of 14c (see compound 17c).
Taking into account the feasible nucleophilic conjugated addition of thiols 13 to 10b, anilines 2 were considered as potential nucleophiles. Therefore, the most nucleophilic p-anisidine (2b) was added to 10b, but no addition product was detected. In spite of this result, a trial was carried out starting from 7a and in the presence of an excess (2.0 mol equiv.) of 2b, followed by the reduction treatment, resulting in a mixture of 11b as the major product and the desired adduct 15 as the minor one (Scheme 3). Due to the difficulty of purifying the latter, the benzyl diarylamine 16 was generated (with compound 12a as the major product) in a one-pot procedure without the isolation of 15. It is worth mentioning that these reactions followed the same chemoselective addition pathway to the imino quinoid system as the thiols 13a-d. The low yields of products 15 and 16, and the fact that other less activated anilines were unable to give the double addition, may be explained by the lower nucleophilicity of anilines with respect to thiols. Also unsuccessful was the conjugated addition of soft nucleophiles, such as dimethyl malonate or nitromethane carbanions to iminoquinone 7a or anilinoquinone 10b, that led to the recovery of the starting materials. In order to increase the number of substituents with valuable functional groups on the phenol ring, we investigated the allylation of phenols 11b-c and 14c and subsequent Claisen rearrangement (Scheme 4). The first reaction proceeded efficiently to give the corresponding allyl ethers 17a-c in high yields. Derivative 17b was submitted to the thermal Claisen rearrangement to furnish the expected [61] pentasubstituted allyl phenol 19b in a modest yield, observing the starting material and decomposition by-products. However, iminoquinone 18a was the main product in the case of 17a, found along with the starting material and by-products (phenol 19a was not isolated). The electron-demand of the para substituent (anilino group) in precursors17a-b is presumably involved In order to increase the number of substituents with valuable functional groups on the phenol ring, we investigated the allylation of phenols 11b-c and 14c and subsequent Claisen rearrangement (Scheme 4). The first reaction proceeded efficiently to give the corresponding allyl ethers 17a-c in high yields. Derivative 17b was submitted to the thermal Claisen rearrangement to furnish the expected [61] pentasubstituted allyl phenol 19b in a modest yield, observing the starting material and decomposition by-products. However, iminoquinone 18a was the main product in the case of 17a, found along with the starting material and by-products (phenol 19a was not isolated). The electron-demand of the para substituent (anilino group) in precursors 17a-b is presumably involved in this unexpected selectivity [62]. The thioaryl analogue 17c was used in NOE experiments to support the HMBC assignment of the structures of derivatives 14a-d. The irradiation of the signal attributed to the methylene group of the allyl moiety generated a selective enhancement of the signal assigned to the ortho (with respect to the sulfur atom) aromatic protons of the thioether group. This result, along with that of other NOE experiments, confirmed that the addition of the thiophenols 13a-d to iminoquinone 10b took place at the imino-quinoid moiety.

Functionalization of bis-Iminoquinone 8a Synthesis of Amino-Diarylamines and bis-Diarylamines
Since the substitution of the isopropylamino group in iminoquinone 7a by anilines 2a-c proceeded to give iminoquinones 10a-c, it was considered that bis-iminoquinone 8a could possibly undergo a mono-or bis-substitution by anilines 2a-e (Scheme 5). Indeed, the addition of 1.0 mol equiv of deactivated anilines 2d-e to bis-iminoquinone 8a resulted in the formation of p-aminodiarylamines 20a-b in low to modest yields. On the other hand, the addition of an excess of anilines 2a-b and 2d produced a double substitution of the two isopropylamino groups by the aniline nucleophiles leading to corresponding bis-iminoquinones 21a-c. The most activated p-anisidine (2b) was the most efficient aniline, while anilines 2a and 2d gave rise to the corresponding bis-iminoquinones 21a and 21c in lower yields, recovering the starting materials and side-products after 24 h of reaction (a longer reaction time afforded traces of the desired products and a deep red resin residue). This behavior is probably due to the lower nucleophilicity of these anilines, an idea supported by the fact that the double substitution did not take place when 8a was submitted to the addition of the deactivated aniline 2e. The thioaryl analogue 17c was used in NOE experiments to support the HMBC assignment of the structures of derivatives 14a-d. The irradiation of the signal attributed to the methylene group of the allyl moiety generated a selective enhancement of the signal assigned to the ortho (with respect to the sulfur atom) aromatic protons of the thioether group. This result, along with that of other NOE experiments, confirmed that the addition of the thiophenols 13a-d to iminoquinone 10b took place at the imino-quinoid moiety.

Functionalization of bis-Iminoquinone 8a Synthesis of Amino-Diarylamines and bis-Diarylamines
Since the substitution of the isopropylamino group in iminoquinone 7a by anilines 2a-c proceeded to give iminoquinones 10a-c, it was considered that bis-iminoquinone 8a could possibly undergo a monoor bis-substitution by anilines 2a-e (Scheme 5). Indeed, the addition of 1.0 mol equiv of deactivated anilines 2d-e to bis-iminoquinone 8a resulted in the formation of p-aminodiarylamines 20a-b in low to modest yields. On the other hand, the addition of an excess of anilines 2a-b and 2d produced a double substitution of the two isopropylamino groups by the aniline nucleophiles leading to corresponding bis-iminoquinones 21a-c. The most activated p-anisidine (2b) was the most efficient aniline, while anilines 2a and 2d gave rise to the corresponding bis-iminoquinones 21a and 21c in lower yields, recovering the starting materials and side-products after 24 h of reaction (a longer reaction time afforded traces of the desired products and a deep red resin residue). This behavior is probably due to the lower nucleophilicity of these anilines, an idea supported by the fact that the double substitution did not take place when 8a was submitted to the addition of the deactivated aniline 2e.
Unlike bis-iminoquinone 8a, which suffers decomposition after remaining several hours at room temperature, bis-iminoquinones 21 are stable red oils or solids under the same conditions. The color of these compounds become yellow in methanol, methylene chloride or toluene solutions, as previously observed for 8b [33].
The reduction of 21b by treatment with sodium hydrosulfite provided bis-diarylamine 22a in high yield (Scheme 5). A one-pot reaction was also tried for the addition of anilines 2c and 2d to 8a, followed by reduction with sodium hydrosulfite, affording bis-diarylamines 22b-c, respectively. These bis-iminoquinones 21 and 1,4-phenylenediamines 22 are of significant importance as conducting polymers [63] and as efficient substrates in electron-transfer [64] and electrochemical studies [65]. 6 20a-b in low to modest yields. On the other hand, the addition of an excess of anilines 2a-b and 2d produced a double substitution of the two isopropylamino groups by the aniline nucleophiles leading to corresponding bis-iminoquinones 21a-c. The most activated p-anisidine (2b) was the most efficient aniline, while anilines 2a and 2d gave rise to the corresponding bis-iminoquinones 21a and 21c in lower yields, recovering the starting materials and side-products after 24 h of reaction (a longer reaction time afforded traces of the desired products and a deep red resin residue). This behavior is probably due to the lower nucleophilicity of these anilines, an idea supported by the fact that the double substitution did not take place when 8a was submitted to the addition of the deactivated aniline 2e. The structure of these compounds was established by spectrometric analyses and X-ray diffraction. Figure 1 shows the X-ray structure of 8a, in which both imino moieties display an (E) configuration. Similarly, NOE experiments showed that bis-iminoquinones 21 possess (E,E) configurations, which is in agreement with previous X-ray diffraction evidence of compound 21a [59] and the bis-iminoquinone derived from 2c [60].

Mechanism of Formation of Compounds 7-9
The proposed mechanism for the formation of compounds 7-9 is depicted in Scheme 6. As proposed by Carlson [33], diacetyl (1a) reacts with the amine to give rise to imino ketone I, which undergoes auto condensation to generate the imino aldol intermediate II. This is cyclized through an internal condensation followed by a loss of water to afford III (an intermediate isolated by Carlson for the case of 6b, but never observed or isolated in our trials), which leads to the isolation of bis-iminoquinones 8 after losing another molecule of water. These compounds undergo reduction to compounds 9 in the middle of the reaction. The latter conversion also takes place when leaving a methanolic solution of 8a at room temperature, which rapidly changes from yellow to a dark color, observing a mixture of 9a with a dark red resin.
Under standardized reaction conditions (Tables 1 and 2), this process seems to be faster than that of the formation of iminoquinones 7, as observed by tlc and 1 H-NMR. Compounds 8 before compounds 7, suggesting that the latter are formed via an independent pathway or through mono-hydrolysis of 8. The second hypothesis is not feasible, because there was no evidence of the formation of 7a when a solution of 8a remained for a long time under the same reaction conditions as those used for the synthesis of both compounds, leading rather to compound 9a and side-products. Therefore, it is presumed that iminoquinones 7 are formed via a pathway that includes the aldol condensation of I with another molecule of 1a to generate aldol IV, which by intramolecular aldolization yields intermediate V. Finally, products 7 are formed by the loss of a water molecule. This hypothesis is supported by the trials displayed in Table 1 (entries 1 and 5), in which only products 7a and 9a were generated by the presence of an excess of 1a in the middle of the reaction. 7 an internal condensation followed by a loss of water to afford III (an intermediate isolated by Carlson for the case of 6b, but never observed or isolated in our trials), which leads to the isolation of bis-iminoquinones 8 after losing another molecule of water. These compounds undergo reduction to compounds 9 in the middle of the reaction. The latter conversion also takes place when leaving a methanolic solution of 8a at room temperature, which rapidly changes from yellow to a dark color, observing a mixture of 9a with a dark red resin. Scheme 6. Proposed reaction mechanism for the formation of iminoquinones 7 and 8, and transamination process from 7 to 10. (Tables 1 and 2), this process seems to be faster than that of the formation of iminoquinones 7, as observed by tlc and 1 H-NMR. Compounds 8 before compounds 7, suggesting that the latter are formed via an independent pathway or through mono-hydrolysis of 8. The second hypothesis is not feasible, because there was no evidence of the formation of 7a when a solution of 8a remained for a long time under the same reaction conditions as those used for the synthesis of both compounds, leading rather to compound 9a and side-products. Therefore, it is presumed that iminoquinones 7 are formed via a pathway that includes the aldol condensation of I with another molecule of 1a to generate aldol IV, which by intramolecular aldolization yields intermediate V. Finally, products 7 are formed by the loss of a water molecule. Scheme 6. Proposed reaction mechanism for the formation of iminoquinones 7 and 8, and transamination process from 7 to 10.

Under standardized reaction conditions
Interestingly, quinone 23 was only isolated in traces from the reaction mixture. It is well known that this quinone results from the condensation of two molecules of diacetyl (1a) under basic conditions [33]. However, we have isolated it as the main product from the reaction between 1a and 2a after purification of the crude mixture by column chromatography using silica gel not pre-treated with triethylamine. This suggests that 23 proceeds from imines 7 and 8 by hydrolysis during the purification process, but not from the reaction.
Another interesting case is that of phenol 24, which was not observed or detected in the reaction mixture by NMR, suggesting that iminoquinones 7 are stable enough to undergo reduction under the reaction conditions. This is in contrast with compounds 8, in which the reductive aromatization takes place during the reaction or the purification process to yield p-dianilinobenzenes 9.
Regarding the transamination process from the iminoquinone 7a to 10a-c and from diiminoquinone 8a to 21a-c, the mechanism can be explained in terms of a series of equilibria promoted by the Brønsted acid catalyst (AcOH) in the presence of anilines 2, as summarized in Scheme 6. It is likely that the first acid-base equilibrium is established between 7 and the amino protonated species VI, and that this undergoes the attack of aniline 2 (which is more nucleophilic and less basic than the alkyl amine) to generate aminal species VII, followed by an elimination of the most basic amine (isopropylamine) to provide the observable aryliminoquinones 10. Additionally, this equilibrium seems to be favored by the higher stability of 10 than alkyliminoquinones 7, resulting from a more stable conjugated imino system. These arguments can also be applied to the transamination from 8a into bis-iminoquinones 21.

General
Melting points were determined with a capillary melting point apparatus. IR spectra were recorded on a Perkin-Elmer 2000 spectrophotometer (PerkinElmer, Waltham, MA, USA). 1 H (300 or 500 MHz) and 13 C (75 or 125 MHz) NMR spectra were recorded on Varian Mercury-300 (Varian, Inc., Palo Alto, CA, USA), and Varian VNMR System instruments (Varian, Inc., Palo Alto, CA, USA), with TMS as internal standard; chemical shifts (δ) are reported in ppm. Assignment of the NMR signals was made by HMQC and HMBC 2D methods (for the 1 H-and 13 C-NMR spectra of the new compounds, see the supplementary figures). Mass spectra (MS) and high-resolution mass spectra (HRMS) were obtained in the electron impact (EI) (70 eV) mode and recorded on Polaris Q-Trace GC Ultra (Finnigan Co., Waltham, MA, USA) and Jeol JSM-GCMateII apparatuses (JEOL, Ltd., Tokyo, Japan), respectively. Elemental analyses were performed on a CE-440 Exeter Analytical instrument (Exeter Analytical, Inc., North Chelmsford, MA, USA), X-ray crystallographic measurements were collected on an Oxford XcaliburS diffractometer (Rigaku Co., Tokyo, Japan). Analytical thin-layer chromatography was carried out using E. Merck silica gel 60 F254 coated 0.25 plates, visualized by a long-and short-wavelength UV lamp. Flash column chromatography was performed over Natland International Co. (Morrisville, NC, USA) silica gel (230-400 mesh) and silica gel (230-400 mesh) pre-treated with trimethylamine (10%). All air moisture sensitive reactions were carried out under nitrogen using oven-dried glassware. MeOH, and toluene were freshly distilled over sodium, as well as methylene chloride over calcium hydride, prior to use. Acetone was dried by distillation after treatment with 4 Å molecular sieves. K 2 CO 3 was dried overnight at 120˝C prior to use. Triethylamine was freshly distilled from NaOH. All other reagents were used without further purification.