Synthesis of substituted pyrroles in the glaser reaction

Article abstract of DOI:10.1002/hc.20184

The substituted pyrroles and dipyrroles along with diacetylenes and cumulenes have been synthesized in high yields using a new synthetic method under mild reaction conditions using the Glaser coupling reaction. Although diacetylenes are formed from 2-prop

Full text of DOI:10.1002/hc.20184

Heteroatom Chemistry
Volume 17, Number 1, 2006
Synthesis of Substituted Pyrroles
in the Glaser Reaction
S. A. Vizer,1 K. B. Yerzhanov,1 and V. M. Dembitsky2
1Bekturov Institute of Chemical Sciences MES Kazakhstan, 106 Sh. Walikhanov Street,
Almaty, 050010, Kazakhstan
2Department of Organic Chemistry, P.O. Box 39231, Hebrew University of Jerusalem,
Jerusalem 91391, Israel
Received 12 October 2005; revised 18 October 2005
The difference being the use of catalytic Cu(I), which
ABSTRACT: The substituted pyrroles and dipyrroles
is reoxidized in the catalytic cycle by oxygen in
along with diacetylenes and cumulenes have been syn-
the reaction medium. The related Hay coupling re-
thesized in high yields using a new synthetic method
action has several advantages as compared to the
under mild reaction conditions using the Glaser
Glaser coupling, see also [3a–f]. The Cu-TMEDA
coupling reaction. Although diacetylenes are formed
complex used is soluble in a wide range of solvents,
from 2-propargyl-1,3-dicarbonyl compounds having
so that the reaction is more versatile [4]. The Glaser
electron-donors substituents such as Ph or OEt,
coupling reaction of terminal alkynes was also re-
only polyfunctional substituted cumulenes are formed
ported in the presence of CuCl2 without organic
from those compounds under the modified condi-
solvents and bases under near-critical water [5]. A
ꢀ
C
tions.
2006 Wiley Periodicals, Inc. Heteroatom Chem
microwave-enhanced, solvent-free Glaser coupling
reaction in the presence of CuCl2 affords good yield
of diacetylenes [6]. A detailed mechanism for the Hay
modification of the Glaser oxidative coupling of ter-
minal acetylenes was formulated on the basis of DFT
calculations [7].
17:66–73, 2006; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.20184
INTRODUCTION
The Glaser coupling reaction was extended to
different organic compounds and used not only for
synthesis of acetylenes with conjugated system of
triple bonds, but as the most important method for
the synthesis of natural products such as amino
acids, ether lipids, polyenes, vitamins, and sugars
[8a–h]. The Glaser–Eglinton–Hay coupling reaction
has been used to synthesize a number of fungal
antibiotics [8i].
The Glaser coupling reaction along with
Eglinton, Straus, and Cadiot–Chodkiewicz and other
coupling reactions have been partly observed in the
preparation of polyacetylenes and synthesis of hete-
rocyclic compounds from/via acetylenes [9].
Here, we report a novel method for the synthe-
sis of the substituted pyrroles and dipyrroles, along
The reaction in which a compound containing an
acetylenic hydrogen was coupled via oxidation of the
Cu(I) acetylide, which was discovered by a German
chemist Carl Glaser (1841–1935) in 1869 [1]. The
Glaser coupling reaction is a synthesis of symmet-
ric or cyclic bisacetylenes via a coupling reaction
of terminal alkynes. More recently, a similar reac-
tion was described by Eglinton [2a–d]. The Eglinton
reaction is an oxidative coupling of terminal alkynes
and allows the synthesis of symmetric or cyclic
bisacetylenes via a reaction of the terminal alkyne
with a stoichiometric Cu(II) salt in pyridine [2e].
Correspondence to: V. M. Dembitsky; e-mail: dvalery@cc.huji.
ac.il.
c
ꢀ
2006 Wiley Periodicals, Inc.
66

Synthesis of Substituted Pyrroles in the Glaser Reaction 67
with diacetylenes and cumulenes using the Glaser
coupling reaction.
Pyrrole 2 and dipyrrole 3 have been isolated by
column chromatography on SiO2. It has to be stored
at the reduced temperature in an inert atmosphere
because they are quickly oxidized and polymerized
at room temperature.
RESULTS AND DISCUSSION
The data of elemental analysis (Table 1), IR,
For the first time an unusual behavior of 3-acetylhex-
5-yn-2-one 1 in the Glaser reaction was established
by us [10]. The oxidative dimerization reaction of
this ꢀ-diketone 1 in water–ethanol solution of am-
monium chloride, when cuprous chloride is used
as a catalyst and oxygen as an oxidant at 50–60◦C,
leads to the formation of two products: 2,5-dimethyl-
3-acetylpyrrole 2 and the corresponding compound
dipyrrole 3. The chromatographic control of the
diketone 1 reaction showed the simultaneous forma-
tion of 2 and 3. Two competitive paths in this pro-
cess are (1) the formation of acetylenic amine A that
leads to pyrrole 2; (2) oxidative coupling leads to di-
acetylenic tetraketone B, that is its dienamine C is
transformed to dipyrrole 3 (Scheme 1).
1
NMR H, 13C spectra, and mass spectra gave com-
position and structure of 2 and 3. IR spectra of pyr-
role 2 and dipyrrole 3 show intensive bands charac-
teristic for valency oscillations of pyrroles ring and a
band characteristic for amide’s system O C C C N
(Table 2). The signal of acetylenic proton disap-
pears in 1H-NMR spectrum of 2 (Table 3), and three
methyl group signals appear at 2.1–2.5 ppm. At 6.1–
6.2 ppm, a broad singlet characteristic for one proton
of pyrrol’s ring is observed. The proton of N–H group
gives a broad singlet at 8.35 ppm.
13C NMR spectra given in Table 4 confirm the
structure of 2,5-dimethyl-3-acetylpyrrole 2. We at-
tributed signals of all carbon atoms by analysis of its
SCHEME 1

68 Vizer, Yerzhanov, and Dembitsky
TABLE 1 Physical and Chemical Characteristics and Analytical Data for Synthesized Compounds
Found, Calculated (%)
Molecular
Formula
mp ( ◦C), (solvent)
Yield
(%)
a
C
H
N
Rf
or bp/Hg mm
2
3
6
8
9
10
11
12
C8H11NO
C16H20N2O2
C13H12O2
70.01, 70.04
70.00, 70.59
8.54, 8.08
7.68, 7.34
–
–
–
–
–
0.5
0.2
81–82 (Hexan)
98–99 (Hexan)
49
65
78.00, 77.98
77.34, 78.37
64.13, 64.66
65.31, 65.49
60.93, 61.22
59.50, 58.40
6.23, 6.04
6.16, 5.75
6.00, 6.63
7.73, 7.24
6.62, 6.16
6.46, 6.24
0.7
0.5
0.6
0.7
0.5
0.5
121–123/1(n2D8 1.5456)
55
51
50
20
36
42
C
26H22O4
C18H22O6
22H29NO6
20H24O8
C22 28O10
–
–
–
–
–
C
3.10, 3.47
C
–
–
H
aSilufol, bzn: ac = 5 : 1.
TABLE 2 IR Data for Synthesized Compounds, ν (cm−1
)
2
1620 (N C C C O), 1360,1376,1448,1524,1552,1592 (Pyrrol), 3160 (N H)
1620 (N C C C O), 1360,1376,1448,1524,1552,1592 (Pyrrol), 3160 (N H)
1680, 1728 (C O), 1544,1600 (Ph), 3312 (≡C H)
3
6
8
1680, 1712 (C O), 1448, 1596 (Ph), 688, 744 (C H, Ph)
9
1744 (C O), 2232 (C≡C), 1180 (C O C)
10
11
12
1670, 1740 (C O), 2230 (C≡C), 1180 (C O C), 3450 (N H)
1706, 1716 (C O), 1648 (C C, enol), 1232,1160 (C O C), 1950 (C C C C)
1690, 1740 (C O), 1264,1184, 1160 (C O C), 1950 (C C C C)
TABLE 3 1H NMR Data for Synthesized Compounds, δ, (ppm) and J (Hz)
2
3
2.20 (3H, s, Pyr CH3); 2.36 (3H, s, Pyr CH3); 2.49 (3H, s, C(O)CH3); 6.14 (1H, br s, Pyr H); 8.35 (1H, br s, NH)
2.31 (6H, s, two Pyr CH3); 2.42 (6H, s, two C(O)CH3); 3.69 (4H, s, CH2 CH2 ); 6.22 (2H, d, J = 2.7, two
Pyr H); 9.40 (2H, brs, two NH)
4
1.99 (1H, t, J = 2.7, ≡C H); 2.06 (3H, s, -CH3); 2.24 (3H, s, C(O)CH3); 3.09 (2H, d, J = 2.7, ≡-CH2-); 10.46
(2H, br s, NH2)
5
6
1.94 (1H, t, J = 3.0, ≡C H); 2.02 (3H, s, -CH3); 2.42 (2H, td, J d = 7.8, J t = 2.4, ≡-CH2 ); 6.14 (1H, m, -H);
9.70 (2H, brs, NH2)
2.00 (1H, t, J = 2.9, ≡C H); 2,17 (2.25H, s, keto form); 2.40 (0.75H, s, enol form); 2.76 (0.75H, qd, J = 6.9, J =
3.0, J= 17.1, CH2 C≡, keto form); 2.91 (0.75H, qd, J = 7.8, 2.4, 17.1, CH2 C≡, keto form); 3.11 (0.5H, d,
J = 2.4, CH2 C≡, enol form); 4.72 (1H, t, J = 7.2); 7.46 8.01 (5H, m Ph); 16.17 (0.25H, s, OH, enol form)
8
2.15 (6H, s, two CH3); 2.88 (4H, qd, J d = 7.5, J d = 6.9, J q = 17.4, J q = 50.1, two CH2 C≡); 4.66 (2H, t, J =
7.1); 7.49 (4H, t, J = 7.8, Ph); 7.61 (2H, tm, J = 7.5, Ph); 7.97 (4H, d, J = 7.5, Ph)
1.28 (6H, t, J = 7.2, two OCH2CH3); 2.28 (6H, s, two C(O)CH3); 2.75 (4H, d, J = 6.9, two CH2- ≡); 3.66 (2H, t,
J = 7.2, CH CH2); 4.21 (4H, d, J = 7.2, two OCH2CH3)
9
10
1.25 (6H, t, J = 7.2, two OCH2CH3); 2.05 (3H, s, CH3); 2.29 (3H, s, CH3); 2.75 (2H, d, J = 7.5, ≡-CH2 CH);
3.22 (2H, s, ≡-CH2-=); 3.50 (2H, dd, J = 5.4, J = 5.7 Hz, N CH2 CH2 O); 3.66 (1H, t, J = 7.5,
≡-CH2 CH ); 3.77 (2H, t, J = 5.7, N CH2 CH2 O); 4.02 (1H, dd, J = 4.5, J = 2.1 Hz, CH2 CH O); 4.10
(2H, q, J = 7.3, O CH2CH3); 4.19 (1H, m, CH2 CH); 6.47 (1H, dd, J = 6.9, J = 14.4 Hz, OCH CH2); 9.48
(1H, t, J = 5.4, NH)
11
12
2.03 (12H (0.25), s, CH3 enol form); 2.18 (6H, s, OC(O)CH3); 2.25 (12H (0.75), s, CH3 keto form); 3.00 (4H (0.75)
d, J= 7.5, CH2 keto form); 3.40 (4H (0.25), s, CH2 enol form); 4.17 (1H, t, J = 6.9, CH keto form); 16.81 (0.5 H,
s, OH enol form)
1.26 (6H, t, J = 7.2, OCH2CH3); 2.18 (6H, s OC(O)CH3, 2.34 (6H, s, OC(O)CH3); 3.03 (4H, qd, J = 8.7, J =
18.3, J = 6.0 Hz, CH2 CH); 4.00 (2H, dd, J = 6.0, J = 8.4, CH2 CH); 4.18 (4H, q, J = 7.2, O CH2CH3)
1
monoresonance spectrum. Mass spectrum and the
supposed scheme of disintegration at an electronic
impact are given in Scheme 2. Earlier, pyrrole 2 has
been synthesized by other methods [11a–d], and it
has depressant effect on the central nervous system
in mice and has side effects in man [11e].
In dipyrrole 3, H NMR spectrum (Table 3) ap-
pears as a singlet from two methylene groups at 3.69
ppm with intensity corresponding to four protons.
Two singlets of methyl groups appear at 2.31 and
2.42 ppm. At 6.22 ppm a doublet appears with 1 JCH
2.7 Hz. Protons of N H groups appear in the low
=

Synthesis of Substituted Pyrroles in the Glaser Reaction 69
TABLE 4 13C NMR (monoresonance) Data for Synthesized Compounds, δ, ppm, J; Hz
2
3
12.3 (q, 1JCH = 128.2, CH3 Pyr); 13.5 (q, 1JCH = 129.4, CH3 Pyr); 28.2 (q, 1JCH = 126.9, CH3 C(O)); 107.5
(d, 1JCH = 169.7, C-3 Pyr); 120.5 (s, C-2 Pyr); 125.2 (s, C-4 Pyr); 133.7 (s, C-1 Pyr); 194.9 (s, C=O)
13.9 (q, 1JCH = 128.3, CH3Pyr); 28.3 (q, 1JCH = 127.0, CH3C(O)); 67.0 (t, 1JCH = 143.4, Pyr CH2CH2 Pyr); 108.3
(d, 1JCH = 172.0, C-3 Pyr); 120.7 (s, C-2 Pyr); 127.1 (s, C-4 Pyr); 135.5 (s, C-1 Pyr); 195.6 (s, C O)
4
6
8
18.5 (t, 1JCH = 261.3, -CH2-≡); 21.4 (q, 1JCH = 128.2, CH3-=); 28.0 (q, 1JCH = 127.0, CH3 C(O)); 67.8 (d,
1JCH = 247.8, ≡C); 83.4 (dt, d 2JCH = 49.8, C≡); 100.3 (s, C ); 160.3 (s, NH2 C ); 196.5 (s, O C )
18.0 ( CH2− ≡); 28.2 (CH3 C(O)); 61.0 (C(O)CHC(O)); 70.0 (≡CH); 80.5 (CH2 C≡); 128.6 (4CH, Ph); 133.6
(1CH, Ph); 136.0 (1C, Ph); 194.4 (C(O)Ph); 201.3 (C(O)Me)
19.1 (t, 1JCH = 140.4, CH2-≡); 28.7 (q, 1JCH = 128.2, CH3 C(O)); 61.1 (d, 1JCH = 133.1, CH); 67.3 (s, ( C≡);
74.5 (t weak resolv., C≡); 129.1 (d, 1JCH = 162.4, C-3 Ph); 129.2 (d, 1JCH = 162.4, C-4 Ph); 134.3 (dm, d 1JCH
= 161.2, m weak resolv., C-4 Ph); 135.9 (t weak resolv., C-1 Ph); 194.4 (s, C(O)-Ph); 201.6 (s, C(O) CH3)
9
14.0 (q, 1JCH = 127.0, CH3 CH2O); 18.0 (dt, t 1JCH = 136.7, d, 2JCH = 3.6, ≡-CH2 CH); 29.5 (q, 1JCH = 128.2,
CH3 C(O)); 57.8 (d, 1JCH = 134.3, CH); 61.9 (t, 1JCH = 149.0, ≡-CH2); 66.6 (s, ≡C C≡); 74.0 (t, 2JCH = 9.8,
≡C CH2); 167.8 (s, C(O)O); 200.7 (s, CC(O)CH3)
10
14.5 (q, 1JCH = 127.0, CH3 CH2O); 15.3 (q, 1JCH = 128.1, CH3-=); 17.6 (t, 1JCH = 132.4, ≡-CH2-=); 18.1
(t, 1JCH = 135.5, CH2); 29.6 (q, 1JCH = 128.2, CH3 C(O)); 42.4 (q, 1JCH = 136.1, N CH2); 57.9 (d, 1JCH
=
127.0, C(O)CHC(O)); 59.1 (t, 1JCH = 150.2, OCH2 CH3); 61.9 (s, ≡C C≡); 63.9 (s, ≡C C≡); 66.8 (t, 1JCH
144.0, OCH2 CH2N); 72.8 (t, weak resolv., CH2 C≡); 78.4 (t, weak resolv., CH2 C≡); 86.9 (td, t 1JCH
=
162.4, d, 2JCH 8.5, ≡-CH2 CH); 87.8 (s, C C N); 151.4 (d, 1JCH = 183.1, CH O); 160.8 (s,
N C C C(O)); 167.8 (s, O C(O) C C N); 169.7 (s, C(O) O); 200.9 (s, C(O) CH3)
11
12
23.0 (q, 1JCH = 128.2, CH3 C(O) , enol); 29.7 (q, 1JCH 127.5, CH3C(O)O); 29.9 (q, 1JCH 128.2, CH3C(O),
keto-form); 41.7 (t, 1JCH 128.2, CH2CH, keto-form); 42.1 (t, 1JCH 125.2, CH2 C , enol); 62.2 (d, 1JCH
131.9, CH, keto-form); 122.5 (s, C O); 192.3 (s, C(O)O); 203.7 (s, C O, keto-form); 205.6 (s, C )
14.0 (q, 1JCH = 127.0, CH3 CH2O); 29.6 (q, 1JCH = 128.2, CH3 C(O)O); 30.0 (q, 1JCH = 128.2, CH3C(O)C);
41.5 (t, 1JCH = 128.2, CH2 C ); 53.7 (d, 1JCH = 131.8, CH CH2); 61.7 (t, 1JCH = 147.7, OCH2 CH3); 125.0
(s, C O); 168.7 (s, C(O)O); 202.3 (s, C(O)CH3); 205.7 (s, C )
SCHEME 2 Mass spectrum fragmentation of pyrrole 2, m/z (int, %): 138 ([M+ + 1] 4), 137 (M +50), 123 (9), 122 (100), 108
(2), 94 (13), 93 (7), 67 (13), 66 (3), 65 (4), 60 (7), 53 (8), 52 (7), 51, (7).
field at 9.4 ppm as a broad singlet with intensity in
two protons. Identification of 3 is confirmed by 13C
NMR spectrum, as shown in Table 4. As against spec-
trum of pyrrole 2, only one signal of methyl group at
12.3 ppm disappears and the novel signal looks like
a triplet in monoresonance spectrum when double
intensity appears at 67.0 ppm from two methylene
groups.
On modification of reaction’s conditions, namely
by replacing ammonium chloride by ammonia, only

70 Vizer, Yerzhanov, and Dembitsky
SCHEME 3
TABLE 5 The Influence of Reagents and Catalyst Concen-
trations on the Yields of 2 and 3
a mixture of enamines 4 and 5 in 4:1 ratio arises 50–
60◦C. Enamine 5 arises from diketone 1 or enamine
4 as a result of deacetylation (Scheme 3). The data
Mole of Reagents
1
of H and 13C NMR spectra of 4 and 5 are given in
Cat.
NH4Cl
Oxidant
Catalyst
2 (%)
3 (%)
Tables 3 and 4, respectively.
Pyrrole 2 is also not formed in the reaction of 1
with ammonium chloride in water–ethanol solution
by CuCl2 catalysis or without catalysis.
The presence of active carbonyl groups in the
molecule of 1 results in a reaction with ammonium
chloride that also gives a complex with cuprous chlo-
ride. The intramolecular addition of amine group
to a carbon–carbon triple bond in 4 occurred by
cuprous chloride catalysis leading to cyclization and
then isomerization to 2 (Scheme 4).
We determined that a variation in CuCl and
NH4Cl concentration influences the yield of 2. Maxi-
mum yield 49% was obtained by using three times ex-
cess of cuprous chloride and ten times excess of am-
monium chloride and oxygen as the oxidant. With-
out continuous bubbling by air, the yield of 2 rather
decreases. Replacing cuprous chloride by palladium
chloride reduces pyrrole 2 yield to 19% and rises
dipyrrole 3’s yield up to 65% with simultaneous in-
crease of reaction time to 24 h (Table 5).
1
1
3
3
3
1
5
10
10
10
Air
Air
O2
Air
Air
Cu2Cl2
Cu2Cl2
Cu2Cl2
Cu2Cl2
PdCl2
22
43
49
46
19
12
18
25
20
65
3-Benzoylhex-5-yn-2-one 6 and 2-acetylpent-4-
ynic acid ethyl ester 7, in the above conditions of the
Glaser reaction, gave only diacetylenic compounds 8
and 9, respectively with 50% yield (Scheme 5).
The specific triplet signal of acetylenic proton at
1
2 ppm disappears from H NMR spectra of tetrake-
tone 8 and diketodiester 9 (Table 3). The signals of
nine types of carbon atoms for 9 and ten types for 8
are in their 13C NMR spectra. The chemical shifts of
most of the carbon atoms are practically unchanged
as against spectra of 6, 7. Only resonance signals
of the triple bond move 3–6 ppm to the high field
(Table 4), and their form in monoresonance spectra
SCHEME 4

Synthesis of Substituted Pyrroles in the Glaser Reaction 71
SCHEME 5
is changed. The signals from two external acetylene
atoms of diacetylenic system look like triplets, but
not as a doublet of triplets as in the spectra of 6
and 7. The signals from two internal acetylene atoms
look like singlet, but not like doublets as it was in
the initial compounds. Attempts to obtain benzoyl
or ethoxycarbonyl containing pyrroles like pyrrole 2
failed. Apparently this caused by the electronic influ-
ence of substituents R.
also is reduced by twofold against 9, but the novel
singlet at 3.22 ppm appears with intensity corre-
sponding to two protons. The formation of monoe-
namine also proves the appearance of signals in
the spectrum corresponding to one vinyl ether of
monoethanol amine substituents (Table 3). The 13C
NMR spectrum also confirmed the structure of 10
(Table 4). The signals of 20 carbon atoms are present
in the spectrum. The novel signals of enamine group
and vinyloxy ethyl substituent also appear.
We have found for the first time that oxida-
tive condensation of 1 and 7 at 55◦C in pyridine–
methanol solution and with the use of cupric acetate
as an oxidant and a catalyst led to the formation of
cumulenes 11 and 12 in accordance with TLC con-
trolling for the course of reaction. The cumulenes 11
and 12 were isolated from the reaction mixture by
column chromatography on SiO2 with 36–42% yield
(Scheme 7).
Diacethylenic group keeps the reaction of di-
acetylenic compounds 8, 9 with primary amines. We
realized that the reaction of diethyl diester of 9 with
vinyl ether of monoethanol amine by refluxing in ab-
solute benzene gives only monoenamine 10 in 20%
˚
yield in the presence of molecular sieves of 4 A and
in twofold amine excess for 6 h (Scheme 6).
In the IR spectrum of 10, bands of conjugated
N C C C O system (1670 cm−1), acetylene bond
(2230 cm−1), and N H group (3450 cm−1) were
1
In IR-spectra of cumulens 11 and 12 the broad
band of valets vibration of C O bonds having two for
11 and three for 12 local maximums is observed in
usual area. The series of intensive absorbtion bonds
found. The H NMR spectrum showed that the in-
tensity of methyne proton’s triplet at 3.66 ppm is re-
duced by twofold as a result of one amine molecule
addition. Intensity of methylene doublet at 2.75 ppm
SCHEME 6

72 Vizer, Yerzhanov, and Dembitsky
Solvents were purified by distillation. Melting
temperatures were determined by Boetius instru-
ment and not corrected. IR spectra were recorded
1
on Specord M-80 for the solution in CCl4. H and
13C NMR spectra were measured on a Mercury-300
spectrometer (300 MHz for 1H, 75.457 MHz for 13C),
using HMDS as an internal standard. Mass spectra
were measured on a HP 5972 instrument under the
standard conditions (EI, 70 eV). The reaction course
and purity of the compounds were monitored by the
TLC on Silufol UV-254 plates in a benzene: acetone
(5:1 or 10:1) mixture using Chromotoscop instru-
ment or I2 for visualization.
SCHEME 7
in the 1160–1260 sm−1 area are connected with vibra-
tions of polar bonds C O C, cumulenes group gave
the absorbtion bands at the 1950 sm−1 (Table 1).
General Procedures of the Glaser Reaction for
2-Propargyl-1,3-dicarbonyl Compounds
1
In the H NMR spectra (Table 3), the signal of
In Water–Ethanol Solution of Ammonium Chlo-
ride by Cuprous Chloride or Palladium Chloride Catal-
ysis. A solution of 1 (or 6 and 7) (0.01 mol) in 15 mL
of EtOH was added to solution of ammonium chlo-
ride (0.1 mol) and catalyst (0.03 mol) in 25 mL water.
The mixture was stirred for 5 h at 50–55◦C with bub-
bling by oxygen or air, and after cooling was poured
into ammoniated brine and extracted with benzene
(5 × 10 mL). Benzene layer was dried over Na2SO4,
and the solvent was removed by a rotary evapora-
tor. The residue (pyrrole 2 and dipyrrole 3 or di-
acetylenes 8, 9) was purified by column chromatog-
raphy on silica gel with elution by benzene and fol-
lowed by benzene–acetone in different ratios (20:1,
10:1, 5:1, 2:1, 1:1).
acetylenic proton disappeared but two new singlets
from methyl protons of acetyl group appears at 2.17–
2.20 ppm area from keto and enolic forms for com-
pound 11 and for compound 12 appears at 2.34 ppm.
The signal of methylene protons of compound 11
looks like a doublet at 3.00 ppm for the ketoform
and as a singlet at 3.40 ppm for the enolic form.
The signals of the corresponding protons of com-
pound 12 look like a quartet of doublets at 3.0 ppm
area.
In the 13C NMR spectra (Table 4) of 11 and 12, the
signals specific to acetylene bond at 70–90 ppm are
absent, but the novel signals for central atoms at the
206 ppm and for end’s atoms of cumulene structure
at 122–125 ppm appear. The signals of the additive
acetyl groups appear at 23–30 ppm for methyl and
169–192 ppm for carbonyl atoms.
In Pyridine–Methanol Solution by Cupric Acetate
Catalysis. Solution of 1or 7 in 10 mL methanol was
mixed with solution of cupric acetate (0.025 mol) in
pyridine (30 mL) and methanol (20 mL). Resulting
mixture was stirred for 4 h at 50–55◦C then cooled,
poured into excess of 3 N HCl at 0◦C and extracted
by ether. Ether layer was dried over Na2SO4. Solvent
was removed by distillation. Residue was purified by
column chromatography on SiO2.
CONCLUSIONS
Various substances were synthesized by the Glaser
reaction for 2-propargyl-1,3-dicarbonyl compounds,
for example, the usual diacetylenes and well-known
and novel heteroatom compounds such as pyrroles
and dipyrroles including cumulenes. Results of the
Glaser reaction for 2-propargyl-1,3-dicarbonyl com-
pounds depend on their structures and experimental
conditions.
Diethyl 2-Methyl
Ethyleneoxyethylaminomethylene-9 Acetyl
deca-4,6-diyndioate 10
EXPERIMENTAL
Solution of 0.5 g (0.0015 mol) 9 and vinyl ether of
monoethanol amine 0.26 g (0.003 mol) in methy-
lene chloride (20 mL) refluxed under molecular
Initially 2-propargyl-1,3-dicarbonyl compounds 1, 6,
and 7 were synthesized by a routine method [12].
Physical characteristics of substances 1 and 7 are
similar to those described in the literature [12,13].
Characteristics of propargyl benzoyl acetone 6 are
given in Tables 1–4 and confirm that its structure.
˚
sieves 4 A for 2 h. Then, reaction mixture was
cooled. Solvent was removed on a rotary evaporator.
Residue was purified by column chromatography on
SiO2.

Synthesis of Substituted Pyrroles in the Glaser Reaction 73
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