A novel facile synthesis of 2,5-di- and 2,3,5-trisubstituted pyrroles

Article abstract of DOI:10.1055/s-2000-7618

Heterocyclization of ketoximes with propyne or allene in superbase systems MOR/DMSO (M = K, Cs; R = H, t-Bu), which leads to 2-alkyl(aryl, hetaryl)-5-methyl- and 2,3-dialkyl-5-methylpyrroles or 2-methyl-4,5,6,7-tetrahydroindole in yields of up to 63%, has been accomplished for the first time. The reaction is mostly regioselective affording mainly or exclusively 2,5-di- and 2,3,5-trisubstituted pyrroles. The minor isomers in most cases are the corresponding 2,4-di- and 2,3,4-trisubstituted pyrroles, only in the case of acetoxime the isomer ratio is ca 1:1. For oximes of methyl isopropyl ketone and pinacolone, the 4-methyl-isomers become predominant (78, 83%, respectively).

Full text of DOI:10.1055/s-2000-7618

PAPER
1585
A Novel Facile Synthesis of 2,5-Di- and 2,3,5-Trisubstituted Pyrroles
Boris A. Trofimov,*a Ol’ga A. Tarasova,a Al’bina I. Mikhaleva,a Nina A. Kalinina,a Lidiya M. Sinegovskaya,a Jochem
Henkelmannb
a A.E. Favorsky Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 1, Favorsky Street, Irkutsk 664033, Russia
Fax +(73952)396046; E-mail: bat@irioch.irk.ru
b BASF Aktiengesellschaft, Ammoniaklaboratorium ZAR/C-M 311, 67056 Ludwigshafen, Germany
Received 2 June 2000; revised 22 June 2000
However, the reaction with acetoxime (Scheme 2,
Abstract: Heterocyclization of ketoximes with propyne or allene in
R1 = Me, R2 = H) performed in systems MOH/DMSO
(M = K, Cs) or KOBu-t/DMSO, both under atmospheric
or elevated pressure, gave a mixture of 2,4- and 2,5-di-
superbase systems MOR/DMSO (M = K, Cs; R = H, t-Bu), which
leads to 2-alkyl(aryl, hetaryl)-5-methyl- and 2,3-dialkyl-5-meth-
ylpyrroles or 2-methyl-4,5,6,7-tetrahydroindole in yields of up to
63%, has been accomplished for the first time. The reaction is most- methylpyrroles (1a and 1b) in a nearly equal ratio.
ly regioselective affording mainly or exclusively 2,5-di- and 2,3,5-
The experimental conditions, yields and product ratios
trisubstituted pyrroles. The minor isomers in most cases are the cor-
(GC, 1H NMR) are presented in Table 1. When excess of
responding 2,4-di- and 2,3,4-trisubstituted pyrroles, only in the case
pure propyne or allene was passed through the reaction
mixture, the unreacted portion was a propyne-allene mix-
ture (from 80:20 to 69:31, correspondingly). Thus, due to
a fast propyne D allene prototropic isomerization under
the reaction conditions, the product is the same irrespec-
tive of whether we start from propyne or allene. This is
supported by the data in Table 1: the reaction temperature
and time do not affect the ratio of pyrroles 1a and 1b.
There is just a slight dependence of the isomer ratio on the
catalyst and pressure of propyne used. Anhydrous CsOH
increases the content of 2,4-dimethylpyrrole in the mix-
ture (Table 1). The total yield of pyrroles 1a and 1b of
45% is achieved in the presence of a catalytic pair CsF/
NaOH. The corresponding N-2-propenylpyrroles 1c and
1d, the products of further addition of the pyrroles to pro-
pyne or allene, are found as byproducts (Scheme 3).
of acetoxime the isomer ratio is ca 1:1. For oximes of methyl iso-
propyl ketone and pinacolone, the 4-methyl-isomers become pre-
dominant (78, 83%, respectively).
Key words: pyrroles, ketoximes, superbase systems, propyne, al-
lene, heterocycles, regioselectivity
The heterocyclization of ketoximes with acetylene in the
system KOH/DMSO1-3 with the formation of O-vinylac-
etoxime as the first step, provides one of the simplest and
most effective methods of pyrrole ring construction
(Scheme 1). The reaction has comprehensively been ex-
amined with acetylene and only in some cases4 the study
was carried out with phenylacetylene. In the present com-
munication the results on the reaction of ketoximes with
the simplest acetylene homolog propyne and its isomer al-
lene are presented.
Apparently, the results show that the acetoximate anion
attacks not only the C-2 atom of propyne or allene, as it is
the case with alkoxide anions,6 but the C-1 atom of prop-
yne as well to form O-2-propenyl- and O-1-propenylace-
toximes, respectively. As a result of the same rearrange-
ments (Scheme 1), O-1-propenylacetoxime affords the
pyrrole 1a (Scheme 4).
Since for propyne and allene, the largest positive charge is
located on the central carbon atom,5 the attack of the oxi-
mate anion at both the compounds should result in the
same adducts, i.e., O-2-propenylketoximes. Therefore,
one could expect here the formation of 5-methyl substitut-
ed pyrroles according to the mechanism shown in Scheme
1, which has been proved in the case of acetylene.1,2
Scheme 1
Synthesis 2000, No. 11, 1585–1590 ISSN 0039-7881 © Thieme Stuttgart · New York

1586
B. A. Trofimov et al.
PAPER
For R1, R2, see Table 2.
Scheme 2
Scheme 3
The attack of acetoximate anion on the allene C-1 atom For methyl ethyl ketoxime, acetophenone and 2-acetyl-
could most likely lead to O-3-propenylacetoxime, which, thiophene oximes, the reaction is slightly less selective:
as known,7 fails to give pyrrole under the same conditions. the content of corresponding 5-methylpyrroles 2b, 6b and
At the same time, prototropic rearrangement of the inter- 8b is 90-92%.
mediate anion, which leads to O-1-propenylacetoxime, is
also possible. O-Propenyloximes have not been isolated in
any one of the runs, probably due to their ability to quickly
rearrange to pyrroles, in contrast to O-vinylacetoxime,
Similar to acetylene-based pyrrolization of ketoximes,1,2
the syntheses include (as minor side reactions) deoxima-
tion of ketoximes (to form ~ 1-3% of the starting ketones)
and the reaction of NH-pyrroles with propyne or allene,
which can be obtained in good yield from acetoxime and
which leads to N-2-propenylpyrroles 1c, 1d or 3d (4-
acetylene in the system KOH/DMSO.8
15%). In this connection, two points are of interest: (i)
analogous to alkoxide anion,6 the pyrrole anions attack
only the C-2 atoms of propyne and allene; and (ii) from
the two dimethylpyrroles 1a and 1b, 2,4-dimethylpyrrole
(1a), having the less shielded NH group, is most readily
propenylated.
Propyne and allene are less reactive than acetylene, as
seen from comparison of the conditions of ketoxime pyr-
Scheme 4
rolization with acetylene (atmospheric pressure, 93-
100 °C, 6-10 h, DMSO containing 4-10% of H2O)1-3 to
those with propyne or allene (115-125 °C, 3-9 h, DMSO
Unlike acetoxime, the oximes of methyl ethyl ketone, cy-
clohexanone, methyl isopropyl ketone, pinacolone, ace-
tophenone, 2-acetylfuran and 2-acetylthiophene with
propyne or allene in the KOH/DMSO system reacted re-
gioselectively (Table 2). The result of the reaction de-
pends on the ketoxime structure and it is determined by
not only electronic, but by steric factors as well. With
branching of the alkyl group at the oxime function, the
content of the 4-methyl isomer increases. In the case of pi-
nacolone-oxime the ratio becomes 17:83 in favor of 4-me-
thylpyrrole (5a). Seemingly, due to steric factors, the
more bulky oximate anion preferably attacks the propyne
C-1 atom. At the same time, the oximes of cyclohexanone
and 2-acetylfuran form 5-methylpyrroles 3b and 7b only.
containing ~ 0.4% of H2O, Tables 1 and 2). From ke-
toximes and acetylene in the KOH/DMSO (~ 0.4% of
H2O), a mixture of pyrroles and N-vinylpyrroles forms al-
ready at 100 °C,1 whilst in the reactions with propyne at
115-125 °C N-propenylpyrroles form in only negligible
amounts. The unsubstituted pyrrole undergoes quantita-
tive vinylation by acetylene in the system KOH/DMSO
under atmospheric pressure at 115-120 °C for 2 hours.9
For comparison, we carried out the reaction of pyrrole
with propyne or allene or their mixture in the same system
at a temperature of 125-135 °C for 5 hours. As a result,
we obtained N-2-propenylpyrrole (9) (Scheme 5) in a
yield of 59% only (unreacted pyrrole remained in the re-
action mixture).
Synthesis 2000, No. 11, 1585–1590 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
A Novel Facile Synthesis of 2,5-Di- and 2,3,5-Trisubstituted Pyrroles
1587
Table 1 Reaction of Acetoxime with Propyne or Allene or Their Mixtures (Scheme 2, R1 = H, R2 = Me)
Propyne/Allene
Ratio
Catalyst, g (mmol)
T (° C)
Time (h)
2,4-
+
2,5-Dimethylpyrroles
Ratio (%)
Yield of 1c,d (%)
Yield (%)
2
80:20c
80:20
80:20c
89:11d
89:11d
100:0
0:100
80:20
80:20
80:20
84:16 e
2KOH◊H2O
5 (76)
80-95a
2
6
4
4
4
6
6
7
4
4
4
1:1
traces
2KOH◊H2O
5 (76)
115-126b
105-110a
100-120a
95-113a
30
21
35
35
41
42
30
32
32
45
1:1
4
4
2KOH◊H2O
5 (76)
1:1
2KOH◊H2O
5 (76)
42:58
43:57
53:47
1:1
11
4
2KOH◊H2O
5 (76)
2KOH◊H2O
5 (76)
118-128b
118-128b
114-122b
112-124b
110-119b
95-112a
5
2KOH◊H2O
5 (76)
5
CsOH◊H2O
14.9(89)
1:1
5
CsF, NaOHf
13.5 (89), 3.56 (89)
59:41
46:54
52:48
4
t-BuOKf
9.6 (85.6)
3
CsF, NaOH
13.5 (89), 3.56 (89)
8
a The reaction was carried out in an autoclave.
b The reaction was carried out in the flask.
c Preliminary reaction mixture was saturated with propyne-allene at r.t. for 7 h.
d Initial pressure of propyne-allene was 4.5 atm, preliminary potassium acetoximate was prepared prior to the reaction.
e Propyne-allene solution in DMSO prepared at r.t. for 1 h was used.
f DMSO <0.2% H2O.
It is noteworthy that in the reaction of methyl ethyl ke- This synthesis of pyrroles from ketoximes and the
toxime with propyne or allene or their mixture (Table 2), available6 propyne or allene or their mixture significantly
it is only the methylene group that contributes to the pyr- extends the scope of pyrrolization of ketoximes with acet-
role ring construction in spite of elevated temperature ylenes. First of all, it enables 5-methyl substituted pyr-
(115-125 °C), no 2-ethyl-5-methylpyrrole being identi- roles with various substituents in the 2 and 3 positions to
fied (Scheme 6).
be obtained much more easily than before.
With acetylene the regioselectivity is not observed under
the same conditions: apart from the methylene group, the
methyl group also gets involved in the reaction and as a re-
GC analysis of the products of the reaction of ketoximes with pro-
pyne or allene or their mixture was performed on an LXM-8MD
sult 2-ethyl-1-vinylpyrrole appears in the reaction mix- chromatograph (column 3.5 m × 3 mm, XE-60 on Chromaton N-
ture.1
AW-HMDS, detector katharometer, gas-carrier He, isothermal con-
Scheme 5
Synthesis 2000, No. 11, 1585–1590 ISSN 0039-7881 © Thieme Stuttgart · New York

1588
B. A. Trofimov et al.
PAPER
Table 2 The Yield and Ratio of Products in the Reaction of Ketoximes with Propyne or Allene (Scheme 2)
R1
R2
Yielda (%)
Ratio (%)
5-Me-pyrrole
Propyne/Allene (%)
4-Me-pyrrole
Me
Me
H
Me
30
60
50, 1a
8, 2a
50, 1b
92, 2b
80:20
95:5
(CH2)4
63
traces
78, 4a
83, 5a
10, 6a
traces
8, 8a
~100, 3b
22, 4b
71:29
93:7
i-Pr
H
H
H
H
H
40
t-Bu
46
17, 5b
90:10
80:20
80:20
69:31
Ph
51
90, 6b
2-furyl
2-thienyl
23b
18c
~100, 7b
92, 8b
a Yield denotes total yield of pyrroles.
b Reaction time 3 h.
c Reaction time 9 h.
ditions, temperature in the column, katharometer and evaporator:
100-190, 200 and 250 °C). Separation of 2,4- and 2,5-dimethylpyr-
roles (1a and 1b) and isolation of N-2-propenylpyrroles 1c, 1d and
3d were carried out on a PAKhV-07 preparative chromatograph
(column 5 m × 10 mm, column temperature 85-170 °C, other pa-
rameters being the same as described above). IR spectra were re-
corded on a Bruker IFS 25 instrument (as films for liquids, KBr
pellets for solids. For most of the pyrrole the n NH absorption is re-
corded in CCl4 ). 1H NMR spectra were run on a Bruker DPX-400
(400.13 MHz) in CDCl3 with HMDS as internal standard. In most
runs the use was made of commercial DMSO containing ~ 0.4% of
H2O. Commercial KOH containing 15% of H2O (2KOH•H2O) was
employed. The starting propyne (Aldrich Chemical Co.) was of
98% purity. The pure allene was prepared by zinc-assisted dechlo-
rination of 2,3-dichloro-1-propene.10
evaporation at 50 Torr, the residue was placed in a column of Al2O3.
At first elution with pentane was performed to isolate 0.56 g (4%)
of N-(2-propenyl)pyrroles (1c and 1d) (purity 82%), mixed with 0.1
g of pyrroles 1a and 1b (separated by preparative GC). The 1c:1d
ratio in the isolated product was 89:11 (1H NMR). Then the column
content was eluted with a 3:1 pentane/Et2O mixture to give 2.33 g
of a 1:1 mixture of 2,4-and 2,5-dimethylpyrroles (1a and 1b) (total
1
yield 30%) (GC, H NMR), which were separated by preparative
GC (Table 1).
Method B, using CsOH/DMSO: A 1-L steel rotating autoclave was
charged with acetoxime (6.25 g, 85.6 mmol), CsF (13.5 g, 89
mmol), NaOH (3.56 g, 89 mmol), and propyne-allene mixture
(84:16, 13.6 g) dissolved in DMSO (~ 0.4% of H2O, 125 mL) at r.t.
The autoclave was heated at 95-112 °C for 4 h. Further treatment
was performed in the same way as described in Method A. As a re-
sult, 0.92 g (8%) of pyrroles 1c and 1d and 3.68 g of 1a and 1b were
prepared (total yield 45%, 52:48 ratio) (Table 1).
2,4-Dimethyl- and 2,5-Dimethylpyrroles (1a and 1b); Typical
Procedures
2,4-Dimethylpyrrole (1a)
Method A, using KOH/DMSO: Into a 250 mL glass flask equipped
with a stirrer, a cooler, a thermometer, a bubbler for propyne supply
and a gas outlet, acetoxime (6.25 g, 85.6 mmol), 2KOH•H2O (5 g,
76 mmol) and DMSO (125 mL) were placed. A propyne-allene
mixture containing 20% of allene (evaporation temperature
~ -15 °C) was passed while stirring for 6 h through the reaction
mixture heated up to 115-125 °C. After cooling to r.t. H2O
(200 mL) was added to the mixture and extracted with Et2O
(4 × 50 mL). The combined Et2O extracts were washed with H2O to
remove DMSO and dried (MgSO4). After distilling off Et2O and
Purity after preparative GC 90%; nD22 1.5002; brown fluid, did not
freeze at -78 °C.
1H NMR: d = 7.58 (br s, 1 H, NH), 6.35 (s, 1 H, H-5), 5.71 (s, 1 H,
H-3), 2.18 (s, 3 H, 2-CH3), 2.05 (s, 3 H, 4-CH3).
IR (film): n = 563, 648, 731, 789, 956w, 985w, 1038w, 1112,
1148w, 1257w, 1290w, 1392, 1418, 1448, 1514w, 1590, 1653,
2870, 2926, 3085, 3119w, 3487 (n NH, in CCl4) cm-1.
Scheme 6
Synthesis 2000, No. 11, 1585–1590 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
A Novel Facile Synthesis of 2,5-Di- and 2,3,5-Trisubstituted Pyrroles
1589
Anal. calcd for C6H9N: C 75.74, H 9.53, N 14.72. Found C 75.70,
H 9.47, N 14.69.
IR (film): n = 772, 812, 897, 1086, 1147, 1236, 1260, 1300, 1316,
1362, 1388, 1428, 1522, 1654, 2841, 2924, 2975, 3084w, 3101w
cm-1.
2,5-Dimethylpyrrole (1b)
Purity after preparative GC ca 100%; nD22 1.5037; light-yellow fluid
freezing at -78 °C.
Anal. calcd for C12H17N: C 82.23, H 9.78, N 7.99. Found C 82.78,
H 9.60, N 7.40.
1H NMR: d = 7.51 (br s, 1 H, NH), 5.72 (s, 2 H, H-3 and H-4), 2.20
(s, 6 H, 2,5-CH3).
2-Isopropyl-4-methylpyrrole (4a) and 2-Isopropyl-5-methyl-
pyrrole (4b)
Isolated as a 78:22 mixture (Table 2); bp 73 °C/10 Torr.
IR (film): n = 562, 649, 770, 993, 1037, 1186, 1259, 1381, 1395,
1419, 1446, 1516, 1595, 2865, 2903, 2927, 2972, 3083, 3106w,
3477 (n NH, in CCl4) cm-1.
1H NMR: protons of pyrrole 4a, d = 7.27 (br s, 1 H, NH), 6.39 (s, 1
H, H-5), 5.75 (s, 1 H, H-3), 2.85 (m, 1 H, CH), 2.07 (s, 3 H, 4-CH3),
1.20 (d, 6 H, 2 CH3); protons of pyrrole 4b, d = 7.27 (br s, 1 H, NH),
5.75 (s, 2 H, H-3, H-4), 2.43 (m, 1 H, CH), 2.22 (s, 3 H, 5-CH3), 1.20
(d, 6 H, 2 CH3).
Anal. calcd for C6H9N: C 75.74, H 9.53, N 14.72. Found C 75.80,
H 9.51, N 14.63.
2,4-Dimethyl-N-2-propenylpyrrole (1c)
Content: 89% mixed with pyrrole 1d.
1H NMR: d = 6.44 (s, 1 H, H-5), 5.75 (s, 1 H, H-3), 4.91 and 4.81 (2
s, 2 H, =CH2), 2.20 (s, 3 H, 2-CH3), 2.08 (s, 3 H, 4-CH3), 2.04 (s, 3
H, CH3).
IR (film): n = 734, 768, 791, 962, 1095, 1115, 1333, 1363, 1383,
1462, 1588, 1652, 2870, 2929, 2962, 3080w, 3098w, 3487 (n NH,
in CCl4) cm-1.
Anal. calcd for C8H13N: C 78.00, H 10.64, N 11.37. Found C 78.11,
H 10.46, N 11.44.
IR (film): n = 622, 719, 751, 785, 877, 1142, 1200, 1352, 1407,
2-tert-Butyl-4-methylpyrrole (5a) and 2-tert-Butyl-5-methyl-
pyrrole (5b)
Isolated as a 83:17 mixture (see Table 2); bp 68 °C/10 Torr.
1H NMR: protons of pyrole 5a, d = 7.86 (br s, 1 H, NH), 6.38 (s, 1
H, H-5), 5.76 (s, 1 H, H-3), 2.07 (s, 3 H, 4-CH3), 1.24 (s, 9 H, t-
C4H9); protons of pyrrole 5b, d = 7.86 (br s, 1 H, NH), 5.75 (s, 2 H,
H-3, H-4), 2.22 (s, 3 H, 5-CH3), 1.25 (s, 9 H, t-C4H9).
1438, 1512, 1653, 2865, 2897, 2924, 2975, 3105w cm-1.
Anal. calcd for C9H13N: C 79.95, H 9.69, N 10.36. Found 79.70, H
9.47, N 10.61.
2,5-Dimethyl-N-2-propenylpyrrole (1d)
Content: 11% mixed with pyrrole 1c.
1H NMR: d = 5.77 (s, 2 H, H-3 and H-4), 5.28 and 4.94 (2 s, 2
H, =CH2), 2.15 (s, 6 H, 2,5-CH3), 1.95 (s, 3 H, CH3).
IR (film): n = 734, 768, 792, 958, 1101, 1120, 1203, 1223, 1255,
1302, 1363, 1395, 1416, 1463, 1507, 1587, 1701, 2869, 2903, 2932,
2963, 3099w, 3495 (n NH, in CCl4) cm-1.
Pyrroles 2a, 4a-6a, 8a, 2b-8b and 3d (Table 2)
These were prepared analogously by Method A.
Anal. calcd for C9H15N: C 78.78, H 11.02, N 10.21. Found C 78.90,
H 10.87, N 10.23.
2,3,4-Trimethylpyrrole (2a)
Identified by 1H NMR spectrum in a mixture with pyrrole 2b;
content: 8%.
4-Methyl-2-phenylpyrrole (6a)
1
1H NMR: d = 7.27 (br s, 1 H, NH), 5.75 (s, 1 H, H-5), 2.18 (s, 3 H,
2-CH3), 1.97 and 1.98 (2 s, 6 H, 3,4-CH3).
Identified by H NMR spectrum in a mixture with the pyrrole 6b
(10%).
1H NMR: d = 8.05 (br s, 1 H, NH), 6.57 and 6.32 (2 m, 2 H, H-5, H-
3), , 2.11 (s, 3 H, 4-CH3). The protons of C6H5 are masked by 6b.
2,3,5-Trimethylpyrrole (2b)
Purity 92% after column chromatography (Al2O3, eluent: hexane)
and distillation; bp 82 °C/22 Torr; nD20 1.5045.
5-Methyl-2-phenylpyrrole (6b)
1H NMR: d = 7.27 (br s, 1 H, NH), 5.60 (s, 1 H, H-4), 2.14 and 2.07
(2 s, 6 H, 2,5-CH3), 1.93 (d, 3 H, 3-CH3, JMe,H-4 = ~ 2 Hz).
Purity 90%; contains 10% of pyrrole 6a; colorless crystals; mp 95-
96 °C (after sublimation).
1H NMR: d = 8.05 (br s, 1 H, NH), 6.37 (dd, 1 H, H-3), 5.93 (m, 1
H, H-4, JH-3, H-4 = 2.8 Hz, JMe, H-4 = 0.8 Hz), 7.38, 7.30, and 7.13 (3
m, 5 H, C6H5), 2.30 (s, 3 H, 5-CH3).
IR (film): n = 638, 648, 785, 1157w, 1296, 1388, 1402, 1441,
1522w, 1609, 2864, 2921, 2968, 3088w, 3477 (n NH, in CCl4) cm-1.
Anal. calcd for C7H11N: C 77.01, H 10.16, N 12.83. Found C 77.12,
H 9.95, N 12.70.
IR (kBr): n = 553, 689, 753, 775, 900, 1040, 1074, 1217, 1253,
1386, 1452, 1475, 1513, 1588, 1604, 2855w, 2923, 3023w, 3044w,
3060w, 3477 (n NH, in CCl4) cm-1.
2-Methyl-4,5,6,7-tetrahydroindole (3b)
Purity 98.8% after column chromatography (Al2O3, eluent: hexane)
and distillation; bp 91 °C/3 Torr; nD21 1.5389.
Anal. calcd for C11H11N: C 84.04, H 7.05, N 8.91. Found C 83.96,
H 7.07, N 8.85.
1H NMR: d = 7.30 (br s, 1 H, NH), 5.61 (s, 1 H, H-3), 2.50 (m, 2 H-
7), 2.40 (m, 2 H-4), 1.77 and 1.71 (2 m, 2 H-5, 2 H-6), 2.50 (s, 3 H,
2-CH3).
2-(2-Furyl)-5-methylpyrrole (7b)
Colorless crystals; mp 39-40 °C (after sublimation).
1H NMR: d = pyrrole ring protons: 8.16 (br s, 1 H, NH); 6.28 (dd, 1
H, H-3), 5.89 (m, 1 H, H-4, JH-3, H-4 = 3.0 Hz, JMe,H-4 = 0.8 Hz; furan
ring protons: 7.28 (dd, 1 H, H-5), 6.37 (dd, 1 H, H-4), 6.24 (dd, 1 H,
H-3, JH-3, H-4 = 3.3 Hz, JH-3, H-5 = 1.0 Hz), 2.27 (s, 3 H, 5-CH3).
IR (film): n = 549, 639, 781, 823w, 922w, 1132, 1234w, 1278,
1307w, 1335w, 1363, 1398, 1443, 1465, 1526, 1605, 1654w, 2846,
2889, 2924, 3087w, 3480 (n NH, in CCl4) cm-1.
Anal. calcd for C9H13N: C 79.95, H 9.69, N 10.36. Found C 79.78,
H 9.60, N 10.40.
IR (KBr): n = 591, 651, 681, 712, 728, 776, 877, 950, 1009, 1037,
1081, 1158, 1212, 1253, 1292, 1317, 1397, 1442, 1515, 1562, 1619,
2905w, 2921w, 2948w, 3110w, 3130w, 3475 (n NH, in CCl4) cm-1.
2-Methyl-N-2-propenyl-4,5,6,7-tetrahydroindole (3d)
Isolated by preparative GC; purity 99%; nD23 1.5240.
Anal. calcd for C9H9NO: C 73.45, H 6.16, N 9.52. Found C 73.39,
H 6.63, N 9.62.
1H NMR: d = 5.68 (s, 1 H, H-3), 5.21 and 4.89 (2 s, 2 H, =CH2), 2.46
(m, 4 H, 2 H-4 and 2 H-7), 1.72 (m, 4 H, 2 H-5and 2 H-66), 2.15 (s,
3 H, 2-CH3), 1.98 (s, 3 H, CH3).
4-Methyl-2-(2-thienyl)pyrrole (8a)
Identified in a mixture with pyrrole 8b; content: 8%.
Synthesis 2000, No. 11, 1585–1590 ISSN 0039-7881 © Thieme Stuttgart · New York

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B. A. Trofimov et al.
PAPER
1H NMR: d = pyrrole ring protons: 7.94 (br s, 1 H, NH), 6.52 (m, 1
H, H-5), 6.23 (m, 1 H, H-3); thiophene ring protons: 7.09 (dd, 1 H,
H-5), H-3, H-4 protons are masked by signals of 8b, 2.10 (s, 3 H, 4-
CH3).
References
(1) Trofimov, B. A.; Mikhaleva, A. I. N-Vinylpyrroles, Nauka:
Novosibirsk, 1984, 262 p (in Russian).
(2) Trofimov, B. A. In The Chemistry of Heterocyclyc
Compounds, Vol. 48; Jones, R. A, Ed.; Wiley: New York,
1992, Part 2, p 131.
(3) Bean, G. P. In The Chemistry of Heterocyclyc Compounds,
Vol. 48; Jones, R. A., Ed; Wiley: New York, 1992, Part 1, p
105.
(4) Trofimov, B. A.; Mikhaleva, A. I.; Korostova, S. E.; Kalabin,
G. A. Khim. Geterocycl. Soed. 1977, 994; Chem. Abstr. 1977,
87, 151933.
5-Methyl-2-(2-thienyl)pyrrole (8b)
Purity 92%; contains 8% of pyrrole 8a; colorless crystals, mp 34-
36 °C (after sublimation).
1H NMR: d = pyrrole ring protons: 7.94 (br s, 1 H, NH), 6.26 (dd,
1 H, H-3), 5.89 (m, 1 H, H-4, JH-3, H-4 = 3.0 Hz, JMe,H-4 = 0.8;
thiophene ring protons: 7.07 (dd, 1 H, H-5), 6.96 (dd, 1 H, H-4),
6.93 (dd, 1 H, H-3, JH-3, H-4 = 3.6 Hz, JH-4, H-5 = 5.0 Hz, JH-3,H-5 = 1.1
Hz), 2.28 (s, 3 H, 5-CH3).
Yurovskaya, M. A.; Afanas’ev, A. Z.; Bundel, Yu. G. Khim.
Geterocycl. Soed. 1984, 1077; Chem. Abstr. 1984, 101,
210914.
IR (KBr): n = 559, 582, 630, 678, 692, 770, 818, 842, 1037, 1081,
1193, 1253, 1340 w, 1394, 1430, 1534, 1594, 2852w, 2901w, 2923,
2966w, 3068w, 3100w, 3464 and 3474 cm-1 (n NH, in CCl4).
Korostova, S. E.; Mikhaleva, A. I.; Trofimov, B. A.;
Shevchenko, S. G.; Sigalov, M. V. Khim. Geterocycl. Soed.
1992, 485; Chem. Abstr. 1992, 117, 233764.
(5) Agre, B. A.; Taber, A. M.; Beregovykh, V. V.; Klebanova, F.
D.; Nekrasov, N. V.; Sobolev, O. B.; Kalechits, I. V. Khim.-
pharm. Zh. 1983, 17, 333; Chem. Abstr. 1983, 98, 160183.
Mueller, W.; Griesbaum, K. J. Org. Chem. 1967, 32, 856.
(6) Taber, A. M.; Mushina, E. A.; Krenzel, B. A. Allenic
Hydrocarbons: Preparation, Properties and Application.
Nauka: Moskow, 1987, 207 p (in Russian).
(7) Trofimov, B. A.; Mikhaleva, A. I.; Petrova, O. V. J. Org.
Chem. USSR 1991, 27, 1713.
(8) Tarasova, O. A.; Korostova, S. E.; Mikhaleva, A. I.; Sobenina,
L. N.; Nesterenko, R. N.; Shevchenko, S. G; Trofimov, B. A.
Zh. Org. Khim. 1994, 30, 810; Chem. Abstr. 1995, 112,
186603.
Anal. calcd for C9H9NS: C 66.22, H 5.56, N 8.58, S 19.64. Found C
66.29, H 5.68, N 8.56, S 20.42.
N-2-Propenylpyrrole (9)
Into a glass flask equipped with a stirrer, a cooler, a thermometer, a
bubbler for propyne supply and a gas outlet, pyrrole (6.7 g, 0.1 mol),
2KOH•H2O (6 g, 92 mmol) and DMSO (60 mL) were placed. A
propyne-allene mixture containing 19% of allene was passed while
stirring for 5 h through the reaction mixture heated up to 125-
135 °C. Then the formed pyrrole 9 was distilled off together with
DMSO at 4-5/Torr (the unreacted pyrrole remained in the solid res-
idue as potassium pyrrolate). The resultant solution was diluted
with H2O, extracted with Et2O (4 × 50 mL), the combined Et2O ex-
tracts were washed with H2O to remove DMSO and dried (MgSO4).
After evaporating the Et2O, the residue was distilled to afford 9;
yield: 6.33 g (59%); bp 147 °C/760 Torr; nD23 1.5174; 99% purity.
(9) Tarasova, O. A.; Mal’kina, A. G.; Mikhaleva, A. I.;
Brandsma, L.; Trofimov, B. A. Synth. Commun. 1994, 24,
2035.
(10) Brandsma, L.; Verkruijsse, H. Studies in Organic Chemistry
8, Synthesis of Acetylenes, Allenes and Cumulenes, Elsevier:
Amsterdam, 1981, p 143.
1H NMR: d = 6.92 (t, 2 H, H-2 and H-5), 6.20 (t, 2 H, H-3 and H-4,
JH-2,H-3 = 2.2 Hz), 4.89 and 4.51 (2 s, 2 H, =CH2), 2.16 [dd, 3 H,
CH3, JMe, = CH2 = 1.2 (trans), 0.5 Hz (cis)].
IR (film): n = 603, 724, 851, 906, 957, 1002, 1048, 1093, 1260,
1306, 1344, 1381, 1438, 1483, 1523, 1553, 1647, 2924, 2955, 2990,
3106, 3140 cm-1.
Article Identifier:
1437-210X,E;2000,0,11,1585,1590,ftx,en;Z05900SS.pdf
Anal. calcd C7H9N: C 78.46, H 8.47, N 13.07. Found C 78.79, H
8.48, N 12.86.
Synthesis 2000, No. 11, 1585–1590 ISSN 0039-7881 © Thieme Stuttgart · New York