First example of autooxidation of methyl and cyclohexano groups attached to the pyrrole ring: stabilization effect of phenyldiazenyl substituents

Methyl substituted 2-phenyldiazenyl-N -vinylpyrroles when refluxed in toluene in the airflow are unexpectedly oxidized at their methyl substituents retaining the pyrrole and N -vinyl moieties intact. The major products of the autooxidation are hydroxyalkyl derivatives (yield up to 60%), the corresponding aldehydes being formed in minor quantities (yield up to 21%). This non-typical oxidation of substituted pyrroles opens a conceptually novel approach to functionalization of phenyldiazenylpyrrole dyes.


Introduction
Pyrroles are known to be easily oxidized on air with the participation of the pyrrole ring. 1 Also is known that the double bonds adjacent to heteroatoms undergo ready autooxidation as well. 2 Recently, we have synthesized a new family of reactive phenyldiazenylpyrrole dyes by direct azo-coupling of N-vinylpyrroles with aryldiazonium salts. 3Further functionalization of these dyes will increase their potential application.For this purpose, a better understanding of their reactivity towards oxidizers appears to be also important, especially having in mind that these functionalized pyrroles attract growing attention. 4SSN 1551-7012 Page 353  ARKAT USA, Inc.

Results and Discussion
Here we report the first examples of a peculiar autooxidation of substituted 2-phenyldiazenyl-Nvinylpyrroles 1a-c and 2-diazenyl-N-vinyl-4,5,6,7-tetrahydroindole 1d which unexpectedly proceeds selectively at 5-methyl substituents and at 7-position of cyclohexane moiety with preserving the pyrrole ring, N-vinyl and azo groups (Scheme 1).The isolated yields of the hydroxy derivatives 2a-d range 18-60%.In the case of pyrroles 1b,c, the minor products of the oxidation are the corresponding aldehydes 3b,c, the yields of which not exceeding 21%.

Scheme 1
The reaction was carried out by refluxing of pyrroles 1a-e in toluene upon passing the air through the reaction mixture for 5-11 h.The oxidation products were isolated by column chromatography.Noteworthy, that when oxygen (instead of air) was employed under the same conditions, the oxidation occurred much faster and no individual products were isolated.
The structure of compounds 2a-d unambiguously follows from the single-crystal X-ray diffraction of compound 2b as a typical representative of this series (Figure 1) in conjunction with the NMR data (see below).The crystalline structure of pyrrole 2b is formed by two crystallographically independent molecules A and B. The conformations of bicyclic parts of both molecules are essentially planar: maximum deviation of atoms out of the averaged plane formed by pyrrole, azo and benzene moieties is 0.10 Å and 0.06 Å for molecules A and B, respectively.Dihedral angles between the pyrrole plane and that of vinyl group are 151.The structure of aldehydes 3b,c was proved by 1 H and 13 C NMR spectra.For 3b, the singlet at 9.97 ppm in the 1 H NMR spectrum together with the 13 C resonance at 180.4 ppm are indicative of the formyl function.2D HSQC and HMBC spectra prove the 5-position of the formyl group.
Apparently, the oxidation of N-vinyl-2-phenyldiazenylpyrroles starts with the formation of the hydroperoxide 4 (Scheme 2) which then decomposes to hydroxyl and methoxyl radicals 5.The latter abstract hydrogen atom from the starting pyrrole 1a-c to give the hydroxymethyl derivatives 2a-c and radical 6 which recombinates with hydroxyl.Analogically, the oxidation of tetrahydroindole derivative 1d can be rationalized.There is a probability that the radicals 5 and 6 are trapped by oxygen from air and not only from hydroxyl radical though in the boiling toluene the partial oxygen pressure should be negligible.

Scheme 2
The formation of aldehydes 3b,c is probably due to the known decomposition of hydroperoxides 4 to release water 6 (Scheme 3).

Scheme 3
The stability of the pyrrole, phenyldiazenyl and N-vinyl moieties is likely a result of the electron transfer from the N-vinylpyrrole scaffold to the azo group as shown in Scheme 4. 3 This long-range electron communication along the whole 2-phenyldiazenyl-N-vinylpyrrole system is facilitated by the essentially planar structure of these molecules as here is evident from the X-Ray data (the dihedral angles between N-vinyl group and pyrrole plane range 25-34º only with a very low rotation barrier 7 , Figure 1).

Scheme 4
Consequently, the susceptibility of the pyrrole ring towards oxidants decreases.Since Nvinyl group is in conjugation with the π-system of the whole molecule 8  , the electron density on the double bond also decreases that explains extraordinary stability of this ethylenic moiety towards the autooxidation.
Notably, that under the same conditions, 2,3-dimethyl-N-vinylpyrrole did not undergo the selective oxidation according to Scheme 1, but oxidized deeper to a black tar wherein neither the pyrrole ring nor N-vinyl group were detectable ( 1 H NMR).This highlights a crucial role of the phenyldiazenyl electron acceptor in the observed unanticipated autooxidation of alkyl substituents in the pyrrole ring.
The substituents effect is in accordance with the above consideration.Actually, an electrondonating substituent in the pyrrole moiety increases, but in the phenyldiazenyl fragment decreases the polarization in the whole conjugation system of the azopyrrole dyes and consequently, the former accelerates and the latter slow down the autooxidation.Stability of Nvinyl group in this system is due to delocalization of electron density of the double bond into the ring and hence the oxidation becomes very slow process.Indeed, when 4-methyl substituent in the pyrrole ring was replaced for less electron-donating hydrogen (pyrrole 1a), the yield of oxidation product 2a dropped to about 18% (even after longer reaction time, 38 h) compared to 60% for pyrrole 1b (5 h), and no aldehyde 3a was discernible in the reaction mixture.Respectively, the introduction of ethoxy substituent (a π-donor) to the para-position of phenyl group (pyrrole 1c) decreased the yield of hydroxy derivative 2c to 22% and 9% of aldehyde 3c was formed ( 1 H NMR). Accordingly, a strong electron-withdrawing substituent NO2 (pyrrole 1e) so deeply polarizes the dye molecule that the addition of water (a product of autooxidation) to the azo group with further rearrangement of the adduct to nitroaniline (43% yield) occurs (Scheme 5).The autooxidation reactions are often induced by traces of metals, but here this is not the case because, in parallel with easy oxidation, the robust stabilization of the pyrrole ring takes place that is not common for the pyrrole chemistry.
The facile selective non-catalyzed oxidation of pyrroles 1a-d, if optimized, may be considered as the simplest atom-economic method for functionalization of phenyldiazenylpyrrole dyes.
To summarize, the first examples of easy selective autooxidation of alkyl substituents at the pyrrole moiety of 2-phenyldiazenyl-N-vinylpyrrole dyes with retaining the pyrrole moiety intact has been revealed.The reaction contributes to fundamentals of autooxidation of practically important functionalized pyrrole compounds, in particular pyrrole dyes and pigments as well as to the chemistry of heteroalkenes (N-vinyl group) and phenyldiazenyl functions.The results also help to better understand the electron communication within conjugated strongly polarized phenyldiazenylpyrrole structural unit.

Experimental Section
General.NMR spectra were run on a Bruker DPX 400 spectrometer [400.13 ( 1 H) MHz, 100.6 MHz ( 13 С)]; СDCl3 as solvent, HMDS as internal standard.Detailed 13 C NMR peak assignments were obtained by careful analysis of HSQC and HMBC 2D NMR spectra.IR spectra were recorded from КBr pellets on a Bruker IFS-25 instrument.Microanalyses were obtained in the A.E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, Russia on an EA FLASH 1112 Series (CHN Analyzer) instrument.
8 and 146.0 o for molecules A and B, respectively.Dihedral angles between the pyrrole planes and that of the hydroxyl substituents (C 5 -CH2-O) equal to 103.4 o and 101.7 o for molecules A and B, respectively.The pyrrole and benzene rings are almost coplanar (dihedral angles are 176.4o and 176.7 o ).