General Papers

ARKIVOC 2010 (ii) 352-359

First example of autooxidation of methyl and cyclohexano groups attached to the pyrrole ring: stabilization effect of phenyldiazenyl substituents
Elena Yu. Schmidt,a Elena Yu. Senotrusova,a Igor A. Ushakov,a Olga N. Kazheva,b Oleg A. Dyachenko,b Grigorii G. Alexandrov,c Andrei V. Ivanova, Albina I. Mikhaleva,a and Boris A. Trofimova* A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 1 Favorsky Str., 664033 Irkutsk, Russian Federation b Institute of Problems of Chemical Physics, Russian Academy of Sciences, 1 Academician N. N. Semenov Str., 142432 Chernogolovka, Russian Federation c N. S. Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation E-mail:

Abstract 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 nontypical oxidation of substituted pyrroles opens a conceptually novel approach to functionalization of phenyldiazenylpyrrole dyes. Keywords: 2-phenyldiazenyl-N-vinylpyrroles, N-vinylpyrrole-2-carbaldehydes, autooxidation 2-hydroxymethyl-N-vinylpyrroles,

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.3 Further 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.4
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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). R2 = NO2 1 2 1 2 2a 18% (1H NMR) 2b 60% 2c 22% 2e is not formed 3a is not formed 3b 21% 3c 9% (1H NMR) 3e is not formed N N N air toluene. In the case of pyrroles 1b. Dihedral angles between the pyrrole planes and that of the hydroxyl substituents (C5-CH2-O) equal to 103. Dihedral angles between the pyrrole plane and that of vinyl group are 151.5. the minor products of the oxidation are the corresponding aldehydes 3b. The isolated yields of the hydroxy derivatives 2a-d range 18-60%.General Papers ARKIVOC 2010 (ii) 352-359 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.c. reflux HO N N N R 2 R1 + O N N N R2 1a R1 = R2 = H 1b R = Me. . Noteworthy.0o for molecules A and B.4o and 176. the oxidation occurred much faster and no individual products were isolated. Inc.c.7o for molecules A and B. respectively.7-tetrahydroindole 1d which unexpectedly proceeds selectively at 5-methyl substituents and at 7-position of cyclohexane moiety with preserving the pyrrole ring. The oxidation products were isolated by column chromatography.7o). R =H 1c R = Me. The conformations of bicyclic parts of both molecules are essentially planar: maximum deviation of atoms out of the averaged plane formed by pyrrole. R = OEt 1e R1 = Me.10 Å and 0.4o and 101.06 Å for molecules A and B. reflux HO N N N 1d 2d 58% 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. that when oxygen (instead of air) was employed under the same conditions. respectively.8 and 146.6. R1 N Me N N R 2 R1 air toluene. the yields of which not exceeding 21%. The pyrrole and benzene rings are almost coplanar (dihedral angles are 176. azo and benzene moieties is 0. The crystalline structure of pyrrole 2b is formed by two crystallographically independent molecules A and B. N-vinyl and azo groups (Scheme 1). ISSN 1551-7012 Page 353 © ARKAT USA. respectively.

for 2b. O(1A)-H(1A) .2.0. . In the NOESY spectra of pyrroles 2b. 1 ISSN 1551-7012 Page 354 © ARKAT USA.2.893(3) Å. ORTEP diagram of 2b.93(3) Å. H(1B)…N(3B) . ORTEP diagram of intermolecular H-bonding N(3)…H-O in the crystalline state of molecule 2b.protons both with 4-Ме.General Papers ARKIVOC 2010 (ii) 352-359 A Figure 1. H(1B)…N(3B) .68-4.171(3)°. respectively.03(3) Å.97(3) Å. Inc.74 ppm) or 7СН-group for 2d (4.75 Å.2. Contacts and angles between the atoms involved in the H-bonding are O(1A)…N(3A) . characteristic are the singlets of the ОН protons (1. B Molecules of 2b are associated in pairs by intermolecular H-bonding N(3)…H-O (Figure 2). the singlets of the protons of the 5-СН2.5 Figure 2.91 ppm) and the signals for the protons of the N-vinyl moiety.с. cross-peaks of 5-СН2.902(3) Å. O(1A)-H(1A)…N(3A) .c (4. Assignments of the 13С signals were based on 2D HSQC and HMBC spectra.00 ppm).64-2. O(1B)…N(3B) .87(3) Å.07 Å and 2. H and 13C NMR spectra are in agreement with the X-ray structure of hydroxy derivatives 2a-d. H(1A)…N(3A) . The sums of Van-der-Waals radii for O…N and N…H equal 3.0.176(3)°. In the 1H NMR spectra of the compounds 2b-d. O(1B)H(1B)…N(3B) .1.and N-vinyl protons are detected.

4 ppm are indicative of the formyl function.c was proved by 1H and 13C NMR spectra. the oxidation of tetrahydroindole derivative 1d can be rationalized. Analogically. Apparently.97 ppm in the 1H NMR spectrum together with the 13C resonance at 180.General Papers ARKIVOC 2010 (ii) 352-359 The structure of aldehydes 3b.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 XRay data (the dihedral angles between N-vinyl group and pyrrole plane range 25-34º only with a very low rotation barrier7. 2D HSQC and HMBC spectra prove the 5-position of the formyl group. Figure 1). R1 1a-c O2 H H O OH 4 R1 2a-c + [HO] N CH2 N N 6 R2 N N N R 2 R1 N -[HO] O 5 N N R 2 1a-c Scheme 2 The formation of aldehydes 3b. the singlet at 9. For 3b. 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. . 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. 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.c is probably due to the known decomposition of hydroperoxides 4 to release water6 (Scheme 3). R1 H H O OH 4 N N N R 2 R1 N -H2O O 3b. 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.c N N R2 Scheme 3 The stability of the pyrrole. Inc. ISSN 1551-7012 Page 355 © ARKAT USA.

but in the phenyldiazenyl fragment decreases the polarization in the whole conjugation system of the azopyrrole dyes and consequently. and no aldehyde 3a was discernible in the reaction mixture. 38 h) compared to 60% for pyrrole 1b (5 h). Actually.3-dimethyl-N-vinylpyrrole did not undergo the selective oxidation according to Scheme 1. the electron density on the double bond also decreases that explains extraordinary stability of this ethylenic moiety towards the autooxidation. This highlights a crucial role of the phenyldiazenyl electron acceptor in the observed unanticipated autooxidation of alkyl substituents in the pyrrole ring. 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 (1H NMR). the susceptibility of the pyrrole ring towards oxidants decreases. Accordingly. Me N N O 1e N H2 O NO2 N O N O H Me H N NO2 N O N Me O + H2 N NO2 polymer Scheme 5 ISSN 1551-7012 Page 356 © ARKAT USA. when 4-methyl substituent in the pyrrole ring was replaced for less electron-donating hydrogen (pyrrole 1a). 2. 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. an electrondonating substituent in the pyrrole moiety increases. 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). but oxidized deeper to a black tar wherein neither the pyrrole ring nor N-vinyl group were detectable (1H NMR). Since Nvinyl group is in conjugation with the π-system of the whole molecule8. Indeed. that under the same conditions. Respectively. the yield of oxidation product 2a dropped to about 18% (even after longer reaction time. Inc.General Papers ARKIVOC 2010 (ii) 352-359 R1 N Me N N R2 Me R1 + N N _ N R2 Scheme 4 Consequently. The substituents effect is in accordance with the above consideration. the former accelerates and the latter slow down the autooxidation. . Notably.

IR spectra were recorded from КBr pellets on a Bruker IFS-25 instrument. if optimized. 5. ISSN 1551-7012 Page 357 © ARKAT USA.6 MHz (13С)]. hereinafter based on the starting pyrrole 1b consumed).1 Hz.1 Hz. Н3). Но). Нm). 2. 1Н. 132. The reaction contributes to fundamentals of autooxidation of practically important functionalized pyrrole compounds. 1Н. 1501. 13С NMR (101. 3JBX 16.15 (s. 11.13 (1H) MHz. 100. 3 JAX 9.diethyl ether = 3 : 1) to give 58 mg of 5-hydroxymethyl-4-methyl2-phenylazo-1-vinylpyrrole 2b (60% yield.9 5-Hydroxymethyl-4-methyl-2-phenylazo-1-vinylpyrrole 2b: Orange crystals (mp 100-102 оС). 1Н. but here this is not the case because. Inc.47 mmol) was refluxed in toluene (3.3 Hz.7 (С3).61 MHz. 2Н.2 (Ср). 1 Н NMR (400.36 (m. 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.5-dimethyl-2-phenylazo-1-vinylpyrrole 1b: The pyrrole 1b (100 mg. Favorsky Irkutsk Institute of Chemistry. 122. НB). 125. NMR spectra were run on a Bruker DPX 400 spectrometer [400. СН2).General Papers ARKIVOC 2010 (ii) 352-359 The autooxidation reactions are often induced by traces of metals. 54.E. in particular pyrrole dyes and pigments as well as to the chemistry of heteroalkenes (N-vinyl group) and phenyldiazenyl functions. Experimental Section General.3 (Ме). 100.78 (m. 147.70 (d. 1Н. 130. Нp). 1.64 (br.55 (s. the residue (103 mg) was column-chromatographed [basic Al2O3 (рН = 8.5 mL) upon passing the air through the reaction mixture for 5 h. 7. СDCl3 as solvent.74 (s. 129. In the case of pyrrole 1e (reaction time 5 h).8 (Сα). in parallel with easy oxidation. 3Н.6 (С4). Siberian Branch of the Russian Academy of Sciences. Compounds 2c. Autooxidation of 4. 7.48 (dd. 1H NMR spectra of nitroaniline correspond to the literature data.0 (С2). HMDS as internal standard. НА). CDCl3): δ 7. only nitroaniline (43% yield) was isolated after column chromatography.7 (СН2). The facile selective non-catalyzed oxidation of pyrroles 1a-d. Russia on an EA FLASH 1112 Series (CHN Analyzer) instrument. IR (KBr) νmax: 1639.45 (m. 2Н. 1Н. 5. 1596. (0. 20 mg of 4-methyl-2-phenylazo-1-vinylpyrrol-5-carbaldehyde 3b (21% yield) and 10 mg of starting pyrrole 1b (90% conversion). .1 Hz.9 (С5).19 (d. 108. 4. Ме). CDCl3): δ 154. After evaporation of the toluene. НX).s. 6. respectively).5 (Сm). Detailed 13C NMR peak assignments were obtained by careful analysis of HSQC and HMBC 2D NMR spectra. 3JAX 9. the robust stabilization of the pyrrole ring takes place that is not common for the pyrrole chemistry.7 (Со).4 (Сβ). 129. 7.1 (Сi).25). Microanalyses were obtained in the A. 2Н. 1Н. hexane .d were obtained similarly (reaction time 11 and 5 h for 2c and 2d. To summarize. ОН). 3JBX 16. may be considered as the simplest atom-economic method for functionalization of phenyldiazenylpyrrole dyes.13 MHz. The results also help to better understand the electron communication within conjugated strongly polarized phenyldiazenylpyrrole structural unit.

1Н. 1095. 1518. Нm). 1020. 3 JAX 9. 3Н. 1309.9 Hz.8 (С-5). 105. 70. 13С NMR δ 153. 1072. 2953.s.50.6 (С-3). 4. 2.5 (Сβ). 3064.64 (br.5 (С-5). 2. 898.35. 3JAX 8. 7-Hydroxy-2-phenylazo-1-vinyl-4. 72. 15. 4. 3Н. 134.6.3) and Russian Foundation for Basic Research (Grant 09-03-00158). H. НB).34 (m. CH2). 100. 7. 969.95 (d. mp 112-114 оС. 3JAX 8. 6. 3JCH2-Me 7. 2924. 812.48. 133.0 Hz. 935.2010. 1599. 556. 1199. 555. 129. 1022. 919. ISSN 1551-7012 Page 358 © ARKAT USA.42 (s. 1398.9 (Сα). 849.15 (d. 23. 6. H. H. 3JBX 15. N. 1258. 17. 12. 3JAX 9. Anal.0 Hz. Ме). 999.2 (C-4). 1205.78 (d.33): C. 3JAX 9.9 (Сm). 1Н.84 (m. Found: C.68 (s. НВ). 1123. 3Jo-m 8. 1441. 5.0 (CH2Me). 129. 147. 129. N. 71. Но). НX).3 (Сα).82 m. OCH2).70 (d.1 (Сm). 6СН2). 6.86. 1Н. 4-Ме). Orange crystals (from hexane).27. 153. 1596. 1Н.00 (br. 733. N. 1115. 124. 821. Нр.48. 1Н NMR δ 7. N. 969. Yield 22 %. 1405. 5. 14.9 Hz. 2H.48 (d.0 (Сα). 2Н. 2.41. НA). 7. 15.40 (d. 7.8 (С-4). 1598.8 (4-Ме).7 Hz. 999. 1Н. 70. 3Н.6 (С-4). mp 90-92 оС. Anal.45 (dd. 616.3 Hz.89.72. IR ν 3118. 1704.57 (s. 3JBX 16. 1481.08 (d. 1372.4 (Со). red crystals (from hexane).9 Hz. НА).7-tetrahydroindole 2d. 5. 1. 1659. 17.08. НX). Yield 58%. Н-3).63. 123.35): C. 15. 766.69. 3H. 13С NMR δ 161. 1Н. 1372.53 (dd. 102.3 Hz. 2Н. H. 1194.08 (q.45 (s. 61. Acknowledgements This work has been carried out under financial support of leading scientific schools by the President of the Russian Federation (Grant NSH-3230. 1473. 122. 1Н. 1450.8 (Сβ).22. 54. 69. 129. 7.74 (dd. 17.4 (С=O).97 (s.5 Hz. 1Н.2 (Сβ).28. НX). 5. 6. H. 5. 1309. 14. 1296.63 m. 123. Calcd for C14H15N3O (241. 7.41. 1Н. 7.48 (m.8 (C-6).90. 3JAX 9. H. Anal. 1525.85 m (2Н. ОН).38.6 (Сi).5 (С-2). 146. 1234. Нm). 1. N. 1Н NMR δ 7. 67. 2. 999.8 (OСН2).9 (С-3).8 (Сi).3 (Сo). 1131. 689. Found: C. 6.06 m.7 (Со). N. 1.12 (s. Calcd for C16H17N3O (267. 32. 3JBX 16. 1Н. 3JBX 15.88 m (2Н. 4-Methyl-2-phenylazo-1-vinylpyrrol-5-carbaldehyde 3b. 129. 130. OCH2Me). 583. 6. 7-СН). 1Н. Found: C. 1148. 4. Нp). 4-СН2).3 (С-7). 1480.9 (С-2).5 (С-5).77 (m. 1495. H. 1258.s. 113.8 (Ср). Н-3).8 (Сm). Found: C. 2Н. 2Н.29): C.General Papers ARKIVOC 2010 (ii) 352-359 1473.28): C. НС=O). 2852.71. 6.4 (С-3).43 (s.8 (С-4). 1Н.5. 3Jo-m 8. НB). 122. 17. 1064. 1154. 1.41. 2Н. Anal. 2-(4-Ethoxyphenylazo)-5-hydroxymethyl-4-methyl-1-vinylpyrrole 2c. 6.5 (Сi). 5.8 (C-5). 17. 2Н. 1Н. Но). 1. 5. 67. 1194.1 Hz. 2. 945. 1296. НA). 97. 5-СН2). 69. Н-3). 1042. 13С NMR δ 180. 3JBX 16. Нm). 2. IR ν 1657.7 (С-2). 987. 7. orange crystals (from hexane).56. 1Н.9 (Ср). 132. 1Н. . 1Н NMR δ 9. 129. 6. 1148.5 Hz.91 (s.55. 1103.49 (s. 149. 1428. 148. 1335.73. 1042. 495.7 Hz. 769.0 Hz. 554. IR ν 1642. 1Н. 1651.2 (Ме).47 m (2Н.1 Hz. 577. 3JBX 16. N.12. ОН). 108. Но). 12.9 (Ср).75 (d. 1296. 64. 848. 1476. Inc. 688.9 (CH2OH).46 (m. 6. 1Н. Calcd for C14H13N3O (239. N. 131. 5.19. 115. 515. mp 80-82 оС. 1304.9 Hz. H. 710. Calcd for C16H19N3O2 (285.

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