Synthesis of functionalized pyrroles by reaction of 3,4-diacetylhexane-2,5- dione with primary amines in water

Article abstract of DOI:10.1080/00397910701316144

3,4-Diacetylhexane-2,5-dione (tetra-acetylethane) undergoes a complex reaction with primary amines in boiling water to produce N-alkyl-3-acetyl-2,5- dimethylpyrroles, together with small quantities of N-alkyl-3,4-diacetyl-2,5- dimethylpyrroles and 2,5-dim

Full text of DOI:10.1080/00397910701316144

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Synthesis of Functionalized Pyrroles by
Reaction of 3,4‐Diacetylhexane‐2,5‐dione
with Primary Amines in Water
Issa Yavari a & Maryam Sabbaghan a
a Department of Chemistry, Tarbiat Modarres University, Tehran, Iran
Published online: 30 Jun 2007.
To cite this article: Issa Yavari & Maryam Sabbaghan (2007): Synthesis of Functionalized Pyrroles by Reaction
of 3,4‐Diacetylhexane‐2,5‐dione with Primary Amines in Water, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 37:11, 1791-1800
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Synthetic Communicationsw, 37: 1791–1800, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701316144
Synthesis of Functionalized Pyrroles by
Reaction of 3,4-Diacetylhexane-2,5-dione
with Primary Amines in Water
Issa Yavari and Maryam Sabbaghan
Department of Chemistry, Tarbiat Modarres University, Tehran, Iran
Abstract: 3,4-Diacetylhexane-2,5-dione (tetra-acetylethane) undergoes a complex
reaction with primary amines in boiling water to produce N-alkyl-3-acetyl-2,5-
dimethylpyrroles, together with small quantities of N-alkyl-3,4-diacetyl-2,5-dimethyl-
pyrroles and 2,5-dimethyl-1H-pyrrol-3-yl-vinyl-acetamides. When the reaction was
carried out in methanol at room temperature, the yields of the latter products increased.
Keywords: cyclization, 3,4-diacetylhexane-2,5-dione, N-heterocycles, Paal–Knorr,
primary amine, pyrrole synthesis, water
INTRODUCTION
Simple N-heterocycles receive considerable attention in the literature as a con-
sequence of their exciting biological properties and their role as pharmaco-
phores.[1] Of these heterocycles, the synthesis, reactions, and biological
activities of pyrroles stand as an area of research in heteroaromatic
chemistry, and this structural motif appears in a large number of pharma-
ceutical agents and natural products.[2] Accordingly, many strategies have
been developed for the preparation of pyrroles.[3] Despite these new develop-
ments, the classical Paal–Knorr[4] reaction remains one of the most attractive
methods for the synthesis of pyrroles.[5]
In recent years, there has been increasing recognition of water as an
attractive medium for many organic reactions.[6,7] The aqueous medium
Received in Poland October 5, 2006
Address correspondence to Issa Yavari, Chemistry Department, Tarbiat Modarres
University, P. O. Box 14115-175, Tehran, Iran. E-mail: yavarisa@modares.ac.ir
1791

1792
I. Yavari and M. Sabbaghan
with respect to organic solvent is less expensive, less dangerous, and more
environmentally friendly. Also, protection and deprotection processes in
organic synthesis can be simplified in aqueous media. Water-soluble
compounds can be reacted directly without the need of derivatization.
As a part of our current studies on the development of new reactions of
organic compounds in water,[8] we report a convenient and facile synthesis
of highly functionalized pyrrole derivatives 3–5 in moderate yields.
RESULTS AND DISCUSSION
The reaction between 3,4-diacetylhexane-2,5-dione (1) and primary amines
in boiling water leads to N-alkyl-3,4-diacetyl-2,5-dimethylpyrroles 3,
together with variable amounts of N-alkyl-3-acetyl-2,5-dimethylpyrroles 4
and 2,5-dimethyl-1H-pyrrol-3-yl-vinyl-acetamide derivatives 5 (Scheme 1).
Compound 1 is a readily available[9] polycarbonyl system, which is apparently
completely enolized in solution, as indicated by NMR spectroscopy.
The reaction of 1 with primary amines 2 in boiling water was completed
1
within 8 h. H and 13C NMR spectra of the crude reaction mixture indicated
the presence of pyrrole derivatives 3–5. This mixture was separated by
column chromatography. The structures of compounds 3–5 were deduced
1
from their elemental analyses, mass spectrometric data, and their H NMR,
13C NMR, and IR spectra. The 1H NMR spectrum of 3a exhibited five
Scheme 1. Synthesis of pyrrole derivatives 3–5 in boiling water. The yields given in
parentheses belong to the reactions performed in methanol at room temperature.

Synthesis of Functional Pyrroles
1793
single resonances for methyl (d ¼ 2.13, 2.40, and 2.48 ppm), methylene
(d ¼ 5.04 ppm), and methine (d ¼ 6.29 ppm) protons. The 13C NMR
spectrum of 3a–g show distinct resonances in agreement with the proposed
structures. A synthesis of 3a has been reported using a two-step
sequence,[10] which involves the propargylation of secondary enaminones
using n-BuLi and propargyl bromide, followed by intramolecular hydroami-
nation catalyzed by silver nitrate.
The 1H NMR spectrum of 4a exhibited three sharp lines for CH3
(d ¼ 2.42 ppm), CH3-CO (d ¼ 2.28 ppm), and methylene (d ¼ 5.06 ppm)
protons. The phenyl moiety appeared as a multiplet at d ¼ 6.91–7.35. The
13C NMR spectrum of 4a showed 10 signals in agreement with the
proposed structure. Partial assignments of these resonances are given in
1
the Experimental section. The H NMR spectra of 4b–4g are similar to
2
those of 4a. Observation of two characteristic doublets with J of about
1
1.2 Hz in the H NMR spectra of 5a–c and 5e–g is consistent with the
presence of C55CH2 protons. The 13C NMR spectrum of 5a exhibited 20
sharp lines in agreement with the proposed structure.
A plausible way for the formation of products 3–5 is proposed in
Scheme 2. The reaction starts by formation of enaminone 7, which is
converted to pyrrole 4 by elimination of water. Compound 4 is attacked by
another molecule of the amine to form enamine 8, which undergoes intramo-
lecular acyl-transfer reaction via 9 and 10 to produce 5. Hydrolysis of 5 can
produce 3. In fact, the N-alkylacetamide derivatives 11 were isolated and
characterized in some of these reactions.
In summary, the presented reactions of 3,4-diacetylhexane-2,5-dione with
primary amines provide a simple entry into the synthesis of functionalized
pyrroles of potential synthetic and pharmaceutical interest from readily
available starting materials. The present procedure has the advantage that
the reaction is performed under neutral conditions and the starting material
Scheme 2.

1794
I. Yavari and M. Sabbaghan
can be used without any activation or modification. The simplicity of the
present procedure makes it an interesting alternative to complex multistep
approaches.[2–5]
EXPERIMENTAL
General
Melting points were measured on a Electrothermal-9100 apparatus and are
uncorrected. IR spectra were measured on a Shimadzu IR-460 spectrometer.
1H and 13C NMR spectra were measured on a Bruker DRX-500 Avance instru-
ment in CDCl3 at 500.1 and 125.7 MHz, respectively d in ppm, J in Hz. EI-MS
(70 eV) was measured on a Finnigan-MAT-8430 mass spectrometer in m/z.
Elemental analyses (C, H, N) were performed with a Heraeus CHN-O-
Rapid analyzer. Primary amines were obtained from Fluka and were used
without further purification. 3,4-Diacetyl-2,5-hexanedione was prepared by
a known method.[9]
General Procedure for the Preparation of 3a, 4a, and 5a
To a stirred solution of 3,4-diacetyl-2,5-hexanedione (0.39 g, 2 mmol) in
methanol (30 mL) the amine (4 mmol) was added dropwise and allowed to
stand for 24 h. The solvent was removed under reduced pressure, and the
mixture of products was obtained as yellow oil. The products were
separated by silica-gel column chromatography (Merck 230–400 mesh)
using n-hexane-EtOAc (4:1) as eluent to afford pure 4 and 5. Compound 3
was eluted using a 7:3 mixture of n-hexane-EtOAc.
Typical Procedure for the Synthesis of 3a, 4a, 5a
To a stirred solution of 1 (0.39 g, 2 mmol) in water (30 mL), the amine
(4 mmol) was added dropwise and refluxed for 24 h. The solvent was
removed under reduced pressure, and the residue was purified by silica-gel
column chromatography (Merck 230–400 mesh) using n-hexane-EtOAc
(4:1) as eluent to afford pure 3 and 5. Compound 4 was eluted using a 7:3
mixture of n-hexane–EtOAc.
Data
N-Benzyl-3-acetyl-2,5-dimethylpyrrole (3a). Yellow oil,[10] yield 0.32 g,
71%. 1H NMR: d ¼ 2.13 (s, CH3), 2.40 (s, CH3), 2.48 (s, CH3), 5.04
(s, CH2), 6.29 (s, CH), 6.88–7.32 (m, 5CH). 13C NMR: d ¼ 11.8 (CH3),

Synthesis of Functional Pyrroles
1795
12.2 (CH3), 28.6 (CH3), 46.6 (CH2), 108.4 (CH of pyrrole), 120.3, 127.8, and
135.1 (3 C of pyrrole), 125.6 (2CH), 127.5 (CH), 128.9 (2CH), 136.8 (Cipso),
195.1 (C55O).
N-(4-Methylbenzyl)-3-acetyl-2,5-dimethylpyrrole (3b). Cream powder, mp
58–598C, yield 0.39 g, 81%. IR (KBr) (nmax/cm21): 1635 (C55O), 1505
(C55C), 1364 (C-N). 1H NMR: d ¼ 2.14 (s, CH3), 2.32 (s, CH3), 2.40
(s, CH3), 2.49 (s, CH3), 5.00 (s, CH2), 6.29 (s, CH), 6.7–7.1 (4H, 2d,
3J ¼ 7.8, CH). 13C NMR: d ¼ 11.8 (CH3), 12.2 (CH3), 21.0 (CH3), 28.6
(CH3), 46.4 (CH2), 108.4 (CH of pyrrole), 120.3, 127.9, and 133.8 (3C of
pyrrole), 125.5 (2CH), 129.6 (2CH), 135.2 (C) 137.1 (C), 195.0 (C55O). EI-
MS: 241(Mþ, 5), 198 (54), 106 (40), 105 (100), 77 (20), 43 (14). Anal.
calcd. for C16H19NO (241.3): C, 79.63; H, 7.94; N, 5.80%. Found: C,
79.55; H, 7.90; N, 5.86%.
N-(4-Methoxybenzyl)-3-acetyl-2,5-dimethylpyrrole (3c). Yellow oil, yield
0.42 g, 81%. IR (KBr) (nmax/cm21): 1640 (C55O), 1605, 1568, and 1506
(C55C), 1367 (C-N), 1245 (C-O). 1H NMR: d ¼ 2.13 (s, CH3), 2.39
(s, CH3), 2.49 (s, CH3), 3.76 (s, OCH3), 4.96 (s, CH2), 6.27 (s, CH), 6.82
(4H, m, 4CH). 13C NMR: d ¼ 11.8 (CH3), 12.2 (CH3), 28.9 (CH3), 46.1
(CH2), 55.2 (OCH3), 108.4 (CH of pyrrole), 120.3, 127.8, and 130.9 (3 C of
pyrrole), 126.8 (2CH), 128.7 (2CH), 132.5 (C), 159.0 (C), 194.9 (C55O).
EI-MS: 257 (Mþ, 6), 242 (23), 214 (43), 120 (87), 119 (100), 43 (27). Anal.
calcd. for C16H19NO2 (257.3): C, 74.68; H, 7.44; N, 5.44%. Found: C,
74.70; H, 7.53; N, 5.51%.
N-(1-Naphthylmethyl)-3-acetyl-2,5-dimethylpyrrole (3d). Yellow crystals,
mp 179–1818C, yield 0.33 g, 60%. IR (KBr) (nmax/cm21): 1637 (C55O),
1
1518 (C55C), 1367 (C-N). H NMR: d ¼ 2.13 (s, CH3), 2.47 (s, CH3), 2.49
(s, CH3), 5.49 (s, CH2), 6.39 (s, CH), 7.32–8.02 (7H, m, 7 CH). 13C NMR:
d ¼ 11.6 (CH3), 12.0 (CH3), 28.7 (CH3), 44.5 (CH2), 108.56 (CH of
pyrrole), 120.6, 128.2, and 135.5 (3C of pyrrole), 121.9 (CH), 122.2 (CH),
125.8 (CH), 126.1 (CH), 126.6 (CH), 128.0 (CH), 129.1 (CH), 130.7 (C),
132.1 (C), 133.5 (C), 197.5 (C55O). EI-MS: 278 (Mþ þ 1, 10), 277 (Mþ,
8), 149 (100), 141 (92), 71 (80), 57 (54), 43 (21). Anal. calcd. for
C19H19NO (277.4): C, 82.28; H, 6.90; N, 5.05%. Found: C, 82.41; H, 6.98;
N, 5.11%.
N-1-(4-Chlorobenzyl)-3-acetyl-2,5-dimethylpyrrole (3e). Yellow crystals,
mp 88–908C, yield 0.42 g, 80%. IR (KBr) (nmax/cm21): 1641 (C55O), 1565
1
and 1512 (C55C), 1347 (C-N). H NMR: d ¼ 2.11 (s, CH3), 2.39 (s, CH3),
2.46 (s, CH3), 5.00 (s, CH2), 6.29 (s, CH), 6.8–7.2 (4H, 2d,
3J ¼ 7.8, CH). 13C NMR: d ¼ 11.7 (CH3), 12.1 (CH3), 28.6 (CH3), 46.6
(CH2), 108.6 (CH of pyrrole), 120.3, 127.7, and 135.4 (3C of pyrrole), 120.5
(C), 127.0 (2CH), 129.1 (2CH), 134.8 (C), 195.0 (C55O). EI-MS: 261 (Mþ,

1796
I. Yavari and M. Sabbaghan
2), 247 (12), 219 (40), 127 (100), 43 (32). Anal. calcd. for C15H16ClNO
(261.7): C, 68.83; H, 6.16; N, 5.35%. Found: C, 68.94; H, 6.21; N, 5.41%.
N-1-(2-Chlorobenzyl)-3-acetyl-2,5-dimethylpyrrole (3f). Cream powder,
mp 65–708C, yield 0.41 g, 79%. IR (KBr) (nmax/cm21): 1642 (C55O),
1
1518 (C55C), 1340 (C-N). H NMR: d ¼ 2.10 (s, CH3), 2.41 (s, CH3), 2.44
3
(s, CH3), 5.06 (s, CH2), 6.32 (s, CH), 6.26 (1H, d, J ¼ 7.62, CH), 7.12–
7.40 (3H, m, 3CH). 13C NMR: d ¼ 11.6 (CH3), 11.9 (CH3), 28.6 (CH3),
44.6 (CH2), 108.6 (CH of pyrrole), 120.6, 127.8, 131.7 (3C of pyrrole),
126.4 (CH), 127.5 (CH) 128.7 (CH), 129.4 (CH), 134.4 (C), 135.1 (C),
195.0 (C55O). EI-MS: 261 (Mþ, 4), 247 (18), 219 (51), 127 (100), 43 (22).
Anal. calcd. for C15H16ClNO (261.7): C, 68.83; H, 6.16; N, 5.35%. Found:
C, 69.03; H, 6.21; N, 5.40%.
N-Ethyl-3-acetyl-2,5-dimethylpyrrole (3g). Yellow oil, yield 0.27 g, 82%.
IR (KBr) (nmax/cm21): 1630 (C55O), 1563 and 1509 (C55C), 1370 (C-N).
3
1H NMR: d ¼ 1.25 (t, J ¼ 11.8, CH3), 2.22 (s, CH3), 2.35 (s, CH3), 2.54
3
(s, CH3), 3.85 (2H, q, J ¼ 11.8, CH2), 6.20 (s, CH). 13C NMR: d ¼ 11.6
(CH3), 12.0 (CH3), 15.5 (CH3), 28.4 (CH3), 38.0 (CH2), 108.2 (CH of
pyrrole), 120.0, 126.8 and 134.2 (3C of pyrrole), 194.8 (C55O). EI-MS: 165
(Mþ, 30), 150 (100), 122 (30), 43 (36). Anal. calcd. for C10H15NO (165.2):
C, 72.69; H, 9.15; N, 8.48. Found: C, 72.54; H, 9.12; N, 8.42%.
N-Benzyl-3,4-diacetyl-2,5-dimethylpyrrole (4a). Brown crystals, mp 101–
1038C, yield 0.05 g, 10%. IR (KBr) (nmax/cm21): 1637 (C55O), 1516 (C55C),
1
1370 (C-N). H NMR: d ¼ 2.28 (s, 2CH3), 2.42 (s, 2CH3), 5.06 (s, CH2),
6.91–7.35 (5H, m, 5CH). 13C NMR: d ¼ 11.3 (2CH3), 31.3 (2CH3), 46.9
(CH2), 123.4 and 132.3 (4C of pyrrole), 125.5 (2CH), 127.8 (CH), 129.1
(2 CH), 135.8 (Cipso), 197.6 (2C55O). EI-MS: 269 (Mþ, 6), 254 (43), 226
(39), 183 (32), 91 (76), 90 (100), 43 (78). Anal. calcd. for C17H19NO2 (269.3):
C, 75.81; H, 7.11; N, 5.20. Found: C, 75.86; H, 7.08; N, 5.24%.
N-(4-Methylbenzyl)-3,4-diacetyl-2,5-dimethylpyrrole (4b). Cream powder,
mp 117–1188C, yield 0.08 g, 14%. IR (KBr) (nmax/cm21): 1663 (C55O),
1
1628 and 1506 (C55C), 1347 (C-N). H NMR: d ¼ 2.23 (s, 2CH3), 2.28
3
(s, CH3), 2.36 (s, 2CH3), 4.98 (s, CH2), 6.77–7.08 (4H, 2d, J ¼ 7.7, 4CH).
13C NMR: d ¼ 11.3 (2CH3), 21.0 (2CH3), 31.2 (CH3), 46.7 (CH2), 123.3
and 132.3 (4C of pyrrole), 132.9 (C), 137.4 (C), 125.5 (2CH), 129.7 (2CH),
197.4 (2C55O). EI-MS: 283 (Mþ, 5), 268 (54), 240 (77), 198 (32), 105
(100), 43 (82). Anal. calcd. for C18H21NO2 (283.4): C, 76.30; H, 7.47; N,
4.94. Found: C, 76.36; H, 7.54; N, 4.90%.
N-(4-Methoxybenzyl)-3,4-diacetyl-2,5-dimethylpyrrole
(4c).
Yellow
powder, mp 65–678C, yield 0.07 g, 12%. IR (KBr) (nmax/cm21): 1656
(C55O), 1631 and 1505 (C55C), 1347(C-N), 1243 (C-O). 1H NMR:

Synthesis of Functional Pyrroles
1797
d ¼ 2.23 (s, 2CH3), 2.35 (s, 2CH3), 3.72 (s, OCH3), 4.95 (s, CH2), 6.80 (4H,
m, 4CH). 13C NMR: d ¼ 11.3 (2CH3), 31.2 (2CH3), 46.4 (CH2), 55.3 (OCH3),
114.5 (2CH), 126.8 (2CH), 123.4 and 129.1 (4C of pyrrole), 132.3 (C), 159.1
(C), 197.5 (2C55O). EI-MS: 300 (Mþþ1, 10), 179 (60), 136 (100), 57 (84), 43
(80). Anal. calcd. for C18H21NO3 (299.4): C, 72.22; H, 7.07; N, 4.68%. Found:
C, 72.68; H, 7.00; N, 4.69%.
N-(1-Naphthylmethyl)-3,4-diacetyl-2,5-dimethylpyrrole (4d). Yellow
powder, mp 165–1678C, yield 0.06 g, 10%. IR (KBr) (nmax/cm21): 1640
1
(C55O), 1517, 1405 (C55C), 1347 (C-N). H NMR: d ¼ 2.27 (s, 2CH3),
2.46 (s, 2CH3), 5.49 (s, CH2), 7.34–8.00 (7 H, m, 7 CH) 13C NMR:
d ¼ 11.2 (2CH3), 31.3 (2CH3), 44.8 (CH2), 122.1 (CH), 125.8 (CH),
126.3 (CH), 126.8 (CH), 128.3 (CH), 129.2 (CH), 128.8 (C), 129.9 (C),
130.9 (CH), 131.1 (C), 121.8 and 131.07 (4C of pyrrole), 197.5 (2C55O).
EI-MS: 319 (Mþ, 5), 141 (100), 115 (78), 43 (45). Anal. calcd. for
C21H21NO2 (319.4): C, 78.97; H, 6.63; N, 4.39%. Found: C, 78.86; H,
6.72; N, 4.37%.
N-1-(4-Chlorobenzyl)-3-acetyl-2,5-dimethylpyrrole (4e). Yellow crystals,
mp 65–678C, yield 0.07 g, 12%. IR (KBr) (nmax/cm21): 1641 (C55O),
1
1600 (C55C), 1380 (C-N). H NMR: d ¼ 2.27 (s, 2CH3), 2.41 (s, 2CH3),
5.03 (s, CH2), 6.8–7.3 (4H, 2d, 2CH). 13C NMR: d ¼ 11.3 (2CH3), 31.2
(2CH3), 46.3 (CH2), 123.6 and 134.5 (4C of pyrrole), 127 and 129.3 (4CH),
132.0 (C), 133.7 (C), 197.5 (2C55O). EI-MS: 304 (Mþ, 9), 289 (67), 261
(67), 219 (45), 126 (100), 43 (53). Anal. calcd. for C17H18 ClNO2 (303.8):
C, 67.21; H, 5.97; N, 4.61%. Found: C, 67.41; H, 6.04; N, 4.73%.
N-1-(2-Chlorobenzyl)-3,4-diacetyl-2,5-dimethylpyrrole (4f). White powder,
mp 143–1478C, yield 0.05 g, 8%. IR (KBr) (nmax/cm1): 1676 (C55O), 1629
and 1507 (C55C), 1346 (C-N). 1H NMR: d ¼ 2.25 (s, 2 CH3), 2.43 (s, 2CH3),
3
5.09 (s, CH2), 6.35 (d, J ¼ 7.6, CH,), 7.18–7.43 (3H, m, 3CH). 13C NMR:
d ¼ 11.2 (2CH3), 31.3 (2CH3), 44.8 (CH2), 123.6 and 132.2 (4C of pyrrole),
126.3 (CH), 127.7 (CH), 129.1 (CH), 129.6 (CH), 131.1 (C), 133.4 (C), 197.5
(2C55O). EI-MS: 304 (Mþ, 7), 289 (60), 261 (56), 219 (41), 126 (100), 43
(58). Anal. calcd. for C17H18 ClNO2 (303.8): C, 67.21; H, 5.97; N, 4.61%.
Found: C, 67.44; H, 6.03; N, 4.72%.
N-Ethyl-3,4-diacetyl-2,5-dimethylpyrrole (4g). White powder, mp
85–908C, yield 0.04 g, 10%. IR (KBr) (nmax/cm21): 1659 (C55O), 1629
1
3
and 1589 (C55C), 1390 (C-N). H NMR: d ¼ 1.27 (t, J ¼ 7.3 Hz, CH3),
3
2.35 (s, 2CH3), 2.38 (s, 2CH3), 3.85 (q, J ¼7.3, CH2). 13C NMR: d ¼ 11.1
(2CH3), 15.4 (2CH3), 31.3 (CH3), 38.38 (CH2), 123.2 and 131.3 (4C of
pyrrole), 197.6 (2 C55O). EI-MS: 208 (Mþ þ 1, 5), 207 (Mþ, 10), 192
(100), 164 (70), 122 (50), 43 (90). Anal. calcd. for C12H17NO2 (207.3): C,
69.54; H, 8.27; N, 6.76%. Found: C, 69.60; H, 8.30; N, 6.78%.

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I. Yavari and M. Sabbaghan
N1-Benzyl-N1-[1-(1-benzyl-2,5-dimethyl-1H-pyrrol-3-yl)vinyl]acetamide
(5a). Yellow oil, yield 0.14 g, 14%. IR (KBr) (nmax/cm21): 1637 (C55O),
1600 shoulder (C55C), 1386 (C-N). 1H NMR: d ¼ 2.10 (s, CH3), 2.14
2
(s, CH3), 2.18 (s, CH3), 4.64 (s, CH2), 5.03 (s, CH2), 4.66 (d, J ¼ 1.2,
2
55CH), 5.00 (d, J ¼1.2, 55CH), 5.84 (s, CH of pyrrole), 6.80–7.30 (10H,
m, 10 CH). 13C NMR: d ¼ 10.9 (CH3), 12.2 (CH3), 22.3 (CH3), 46.6 (CH2),
49.5 (CH2), 105.7 (CH of pyrrole), 108.5 (C55CH2), 116.3, 126.9. and
128.3 (3C of pyrrole), 125.5 (2CH), 127.0 (CH), 127.3 (2CH), 128.1 (2CH),
128.9 (2CH), 129.0 (CH), 138.1 (Cipso), 137.8 (Cipso), 142.9 (CH255C),
170.7 (C55O). EI-MS: 359 (Mþ þ 1, 7), 344 (17), 316 (38), 273 (36), 268
(40), 91 (87), 90 (100), 43 (52). Anal. calcd. for C24H26N2O (358.5): C,
80.41; H, 7.31; N, 7.81%. Found: C, 80.50; H, 7.33; N, 7.86%.
N1-f1-[2,5-Dimethyl-1-(4-methylbenzyl)-1H-pyrrole-3-yl]vinylg-N1-(4-meth-
ylbenzyl)acetamide (5b). Yellow oil; yield 0.13 g, 12%. IR (KBr) (nmax/cm):
1
1643 (C55O), 1507 (C55C), 1367 (C-N). H NMR: d ¼ 2.10 (s, CH3), 2.14
(s, CH3), 2.18 (s, CH3), 2.40 (s, CH3), 2.49 (s, CH3), 4.60 (s, CH2), 5.03
2
2
(s, CH2), 4.66 (d, J ¼ 1.2, 55CH), 5.00 (d, J ¼ 1.2, 55CH), 5.84 (s, CH of
pyrrole), 6.8–7.3 (8H, m, 8CH). 13C NMR: d ¼ 11.8 (CH3), 12.2 (CH3), 21.1
(CH3), 23.3 (CH3), 28.6 (CH3), 43.6 (CH2), 46.4 (CH2), 108.3 (CH of
pyrrole), 108.5 (C55CH2), 120.1, 127.9 and 129.01 (3C of pyrrole), 125.5
(2CH), 127.9 (2CH), 129.4 (2CH), 129.5 (2CH), 135.2 (C), 133.7 (C), 137.2
(C), 137.3 (C), 148 (CH255C), 170.0 (C55O). EI-MS: 387 (Mþ þ 1, 6), 372
(14), 344 (32), 302 (28), 282 (21), 177 (18), 105 (100), 43 (67). Anal. calcd.
for C26H30N2O (386.5): C, 80.79; H, 7.82; N, 7.25%. Found: C, 80.85; H,
7.76; N, 7.31%.
N1-(4-Methoxybenzyl)-N1-f1-[1-(4-methoxybenzyl)-2,5-dimethyl-1H-pyr-
ol]vinylgacetamide (5c). Yellow oil, yield 0.13 g, 17%. IR (KBr) (nmax
/
1
cm21): 1637 (C55O), 1610 and 1504 (C55C), 1375 (C-N), 1244 (C-O). H
NMR: d ¼ 2.10(s, CH3), 2.14 (s, CH3), 2.15 (s, CH3), 3.77 (s, OCH3), 3.78
2
(s, OCH3), 4.62 (s, CH2), 5.00 (s, CH2), 4.57 (d, J ¼ 1.2, 55CH), 4.97 (d,
2J ¼ 1.2, 55CH), 5.83 (s, CH), 6.78–6.86 (m, 8CH). 13C NMR: d ¼ 11.0
(CH3), 12.3 (CH3), 22.3 (CH3), 55.2 (OCH3), 55.3 (OCH3), 46.3 (CH2),
49.5 (CH2), 105.7 (CH of pyrrole), 111.1 (C55CH2), 128, 129.8, and 129.9
(3C of pyrrole), 113 (2CH), 114.3 (2CH), 126.7 (2CH), 126.8 (2CH), 129.8
(C), 130.4 (C), 158.9, 158.7 (2CO), 142.0 (CH255C), 170.6 (C55O). EI-MS:
419 (Mþ þ 1, 5), 404 (11), 376 (18), 334 (24), 179 (86), 149 (100), 136
(90), 121 (79), 57 (90), 43 (38). Anal. calcd. for C26H30N2O3 (418.5): C,
74.61; H, 7.22; N, 6.69%. Found: C, 74.43; H, 7.31; N, 6.72%.
N1-(4-Chlorobenzyl)-N1-f1-[1-(4-chlorobenzyl)-2,5-dimethyl-1H-pyrrol-3-yl]
vinylgacetamide (5e). Yellow oil, yield 0.14 g, 7%. IR (KBr) (nmax/cm21):
1
1648 (C55O), 1514 (C55C), 1349 (C-N). H NMR: d ¼ 2.07 (s, CH3), 2.12
2
(s, CH3), 2.17 (s, CH3), 4.58 and 5.02 (2s, 2CH2), 4.65 (d, J ¼ 1.2, 55CH),

Synthesis of Functional Pyrroles
1799
2
4.99 (d, J ¼ 1.2, 55CH), 5.83 (s, CH), 6.81–7.30 (8H, m, 8CH). 13C NMR:
d ¼ 11.0 (CH3), 12.2 (CH3), 22.2 (CH3), 46.3 (CH2), 48.8 (CH2), 105.9 (CH
of pyrrole), 111.4 (CH255C), 116.3, 126.7, and 136.5 (3C of pyrrole), 126.7
(2CH), 126.9 (2CH), 128.3 (2CH), 129.1 (2CH), 130.4 (C), 132.9 (C), 133.3
(C), 136.3 (C), 142.7 (CH255C), 170.0 (C55O). EI-MS: 428 (Mþ þ 1, 5),
413 (16), 385 (32), 343 (25), 127 (43), 125 (100), 57 (74), 43 (51). Anal.
calcd. for C24H24Cl2N2O (427.4): C, 67.45; H, 5.66; N, 6.55%. Found: C,
67.65; H, 5.72; N, 6.59%.
N1-(2-Chlorobenzyl)-N1-f1-[1-(2-chlorobenzyl)-2,5-dimethyl-1H-pyrrol-3-yl]
vinylg acetamide (5f). Brown oil, yield 0.14 g, 5%. IR (KBr) (nmax/cm21):
1644 (C55O), 1514 and 1427 (C55C), 1371 (C-N). 1H NMR: d ¼ 2.04
(s, CH3), 2.10 (s, CH3), 2.26 (s, CH3), 4.84 (s, CH2), 5.05 (s, CH2), 4.82 (d,
2J ¼ 1.2, 55CH), 4.99 (d, 2J ¼ 1.2, 55CH), 5.87 (s, CH), 6.27 (d, CH,
3J¼7.5 Hz), 7.16–7.40 (7H, m, 7CH). 13C NMR: d ¼ 11.6 (CH3), 11.9
(CH3), 28.6 (CH3), 41.6 (CH2), 44.6 (CH2), 108.6 (CH of pyrrole), 111.2
(CH255C), 115.3, 126.6, and 127.5 (3C of pyrrole), 127.2 (CH), 127.8 (CH),
128.3 (CH), 128.6 (CH), 128.7 (CH), 129.0 (CH), 129.3 (CH), 130.4 (CH),
129.2 (C), 129.4 (C), 129.5 (C), 134.4 (C), 142.0 (CH255C), 170.0 (C55O).
EI-MS: 428 (Mþ þ 1, 6), 413 (13), 385 (45), 343 (23), 127 (51), 125
(100), 57 (47), 43 (60). Anal. calcd. for C24H24Cl2N2O (427.4): C, 67.45; H,
5.66; N, 6.55%. Found: C, 67.54; H, 5.71; N, 6.63%.
N-Ethyl-N-[1-(1-ethyl-2,5-dimethyl-1H-pyrrol-3-yl)vinyl]-acetamide (5g).
Yellow oil, yield 0.08 g, 4%. IR (KBr) (nmax/cm21): 1643 (C55O), 1610
1
3
and 1510 (C55C), 1380 shoulder (C-N). H NMR: d ¼ 1.10 (t, J ¼ 7.1,
3
CH3), 1.25 (t, J ¼ 7.2, CH3), 2.10 (s, CH3), 2.2 (s, CH3), 2.25 (s, CH3),
3.46 (q, 2J ¼ 7.1, CH2), 3.82 (q, 2J ¼ 3.27, CH2), 4.86 (d, 2J ¼ 1.2,
55CH), 5.12 (d, 2J ¼ 1.2, 55CH), 5.78 (s, CH). 13C NMR: d ¼ 10.9
(CH3), 12.1 (CH3), 12.9 (CH3), 15.9 (CH2), 22.3 (CH2), 38.2 (CH3), 40.6
(CH3), 105.4 (CH of pyrrole), 109.5 (C55CH2), 115.8, 125.6 and 127.2
(3C of pyrrole), 138.0 (CH255C), 170.3 (C55O). EI-MS: 235 (Mþ þ 1, 8),
220 (32), 192 (43), 159 (21), 57 (65), 43 (100), 28 (54). Anal. calcd. for
C14H22N2O (234.3): C, 71.76; H, 9.46; N, 11.95%. Found: C, 71.84; H,
9.60; N, 12.02%.
N1-(Naphthylmethyl)acetamide (11d). White powder, mp 155–1578C, yield
0.11 g, 30%. IR (KBr) (nmax/cm21): 3440 (NH), 1622 (C55O), 1539 and 1501
(C55C). 1H NMR (CD3OD): d ¼ 1.9 (s, CH3), 4.6 (s, CH2), 7.51–8.11
(m, 7CH).
N1-(2-Chlorobenzyl)acetamide (11f). Cream powder, mp 126–1288C, yield
1
0.07 g, 20%. IR (KBr) (nmax/cm–1): 3440 (NH), 1510, shoulder (C55O). H
NMR (CD3OD): d ¼ 1.89 (s, CH3), 4.19 (s, CH2), 7.37–7.53 (m, 4CH).

1800
I. Yavari and M. Sabbaghan
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