DERIVATIVES OF FUROPYRROLE

Full text of DOI:10.1135/cccc19940473

New Compounds
473
DERIVATIVES OF FURO[3,2-b]PYRROLE
Alzbeta KRUTOSIKOVA, Miloslava DANDAROVA and Vladimir BOBOSIK
Department of Organic Chemistry,
Slovak Technical University, 812 37 Bratislava, The Slovak Republic
Received December 22, 1992
Accepted May 24, 1993
As a part of our program aimed at developing efficient syntheses of condensed nitrogen
containing heterocycles, we have reported in the past1,2 efficient syntheses of the title
compounds. In continuation of this work we here report the syntheses of some repre-
sentatives of title ring systems.
A number of methyl 2-substituted, 2,3-disubstituted-4H-furo[3,2-b]pyrrole-5-carbo-
xylates (V – VII) and methyl 1H-benzo[b]furo[3,2-b]pyrrole-2-carboxylate (VIII) was
prepared by the thermolysis of corresponding methyl 2-azido-3-(R1,R2-substituted-2-
furyl)propenoates (I – IV). N-Methyl and N-benzyl derivatives IX – XVI were prepared
at the phase-transfer catalysis conditions. Hydrolysis of some N-methyl and N-benzyl
substituted esters furnished corresponding acids XVII – XXII. The hydrazides XXIII –
XXX were obtained from corresponding esters and hydrazine hydrate. The preparation
of 1-benzylbenzo[b]furo[3,2-b]pyrrole (XXXI) is described as well.
EXPERIMENTAL
Melting points were determined on a Kofler hot plate apparatus and are uncorrected. 1H NMR and
1
13C NMR spectra were recorded on a Tesla BS 587 (80 MHz for H and 20.18 MHz for 13C) spec-
trometer (TMS as internal standard). UV spectra were measured on a M-40 (Zeiss, Jena) spectro-
photometer in ethanol (λmax/log ε; λmax in nm, ε in m2 mol−1). The IR spectra were recorded on a
FTIR PU 9802/25 (Philips) spectrophotometer using KBr technique (0.5 mg/300 mg KBr, ν given
in cm−1).
Characteristic data of synthesized compounds are given in Table I. The structure of the syn-
thesized compounds has been confirmed by 1H NMR spectroscopy (Tables II and III). IR and UV
1
spectra are presented in Table IV. The H NMR and 13C NMR data of compounds I – IV are given
in Experimental.
Compounds I – IV exist as Z isomers. This fact was established from 13C NMR spectra of the
compound II on the basis of the value of vicinal coupling constant 3J(CO, H-6) = 5.0 Hz. The
measured coupling constant is comparable to those of analogous compounds, as are ethyl 2-azido-3-
(5-X-2-furyl)propenoates and 2-azido-3-(4,5-dimethyl-2-furyl)propenoate, which were studied in our
earlier papers3,4
.
The following starting compounds were prepared: 4,5-dimethyl-2-furaldehyde according to ref.5,
5-(4-chloro-2-methylphenoxy)-2-furancarbaldehyde according to ref.6, benzo[b]furan-2-carbaldehyde
according to ref.7 and 1-acetylbenzo[b]furo[3,2-b]pyrrole according to ref.8.
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Krutosikova, Dandarova, Bobosik:
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

New Compounds
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Methyl 2-Azido-3-(5-methyl-2-furyl)propenoate (I)
A solution of 5-methyl-2-furancarbaldehyde (2.2 g, 0.02 mol) and methyl azidoacetate (9.2 g,
0.08 mol) was added at 0 °C during 30 min to sodium metal (1.84 g, 0.08 mol) in methanol (60 ml).
Stirring was continued for additional 60 min at temperature not exceeding 5 °C, the reaction mixture
was then cooled to 0 °C, a solution of ammonium chloride (4.4 g, 0.08 mol) in water (10 ml) was
added and poured in ice water. The separated precipitate was filtered off and crystallized. Yield
2.57 g (62%); m. p. 30 – 32 °C (methanol). For C9H9N3O3 (207.2) calculated: 52.17% C, 4.4% H,
20.28% N; found: 52.26% C, 4.40% H, 20.44% N. IR spectrum: 2 118 (N3), 1 707 (C=O). UV spec-
trum: 343 (3.40). 1H NMR spectrum (CDCl3): 7.00 d, 1 H (H-3, J3,4 = 3.2); 6.81 s, 1 H (H-6);
6.12 bd, 1 H (H-4); 3.86 s, 3 H (OCH3); 2.33 bs, 3 H (CH3). Using the same method the compounds
II – IV were prepared:
Methyl 2-azido-3-(4,5-dimethyl-2-furyl)propenoate (II): Yield 66%; m. p. 51 – 55 °C (methanol).
For C10H11N3O3 (221.2) calculated: 54.29% C, 5.01% H, 19.00% N; found: 53.99% C, 4.96% H,
19.02% N. IR spectrum: 2 124 (N3), 1 713 (C=O). UV spectrum: 352 (3.45). 1H NMR spectrum
(CDCl3): 6.92 s, 1 H (H-3); 6.78 s, 1 H (H-6); 3.86 s, 3 H (OCH3); 2.24 bs, 3 H (C5-CH3); 1.97 bs,
3 H (C4-CH3). 13C NMR spectrum (CDCl3): 163.9 (CO), 150.5 (C-5), 146.8 (C-2), 120.6 (C-7),
119.3 (C-3), 117.9 (C-4), 114.3 (C-6), 52.6 (O-CH3), 11.6 (C5-CH3), 9.8 (C4-CH3), 3J(CO, H-6) =
5.0 Hz.
Methyl 2-azido-3-[5-(4-chloro-2-methylphenoxy)-2-furyl]propenoate (III): Yield 54%; m. p.
47 – 49 °C (methanol). For C15H12ClN3O4 (333.7) calculated: 53.99% C, 3.68% H, 12.59% N;
found: 53.82% C, 3.41% H, 12.68% N. IR spectrum: 2 126 (N3), 1 711 (C=O). UV spectrum: 350
1
(3.45). H NMR spectrum (CDCl3): 7.04 d, 1 H (H-3, J3,4 = 3.5); 6.72 s, 1 H (H-6); 6.80 – 7.28 m,
3 H (H arom.); 5.46 d, 1 H (H-4); 3.86 s, 3 H (OCH3); 2.27 s, 3 H (CH3).
Methyl 2-azido-3-(2-benzo[b]furyl)propenoate (IV): Yield 68%; m. p. 107 – 110 °C (methanol).
For C12H9N3O3 (243.2) calculated: 59.26% C, 3.73% H, 17.28% N; found: 59.16% C, 3.68% H,
17.16% N. IR spectrum: 2 116 (N3), 1 715 (C=O). UV spectrum: 347 (3.61). 1H NMR spectrum
(CDCl3): 7.45 s, 1 H (H-3); 6.94 s, 1 H (H-6); 7.10 – 7.60 m, 4 H (H arom.); 3.91 s, 3 H (OCH3).
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Krutosikova, Dandarova, Bobosik:
TABLE I
Characteristic data of synthesized compounds V – XXXI
Calculated/Found
Formula
(M.w.)
M.p., °C
(Yield, %)
Compound
% C
% H
% N
V
C9H9NO3
(179.2)
135 – 137
60.33
60.12
5.06
5.10
7.82
7.68
(67)
VI
C10H11NO3
(193.2)
230 – 231
62.17
62.28
5.74
5.72
7.25
7.46
(72)
VII
VIII
IX
C15H12ClNO4
(305.7)
134 – 135
58.93
58.82
3.96
3.78
4.58
4.40
(36)
C12H9NO3
(215.2)
203 – 204
66.97
66.92
4.22
4.16
6.51
6.38
(76)
C10H11NO3
(193.2)
30 – 32
62.17
62.32
5.44
5.67
7.25
7.34
(69)
X
C11H13NO3
(207.2)
107 – 108
63.75
63.58
6.32
6.56
6.76
6.82
(73)
XI
C16H14ClNO4
(319.7)
97 – 98
60.10
59.96
4.71
4.76
4.38
4.52
(46)
XII
XIII
XIV
XV
XVI
XVII
C13H11NO3
(229.2)
114 – 115
68.11
68.32
4.84
4.76
6.11
6.02
(72)
C16H15NO3
(269.3)
109 – 111
71.36
71.44
5.61
5.72
5.20
5.38
(56)
C17H17NO3
(283.3)
112 – 115
72.06
72.06
6.05
6.15
4.94
5.02
(58)
C22H18ClNO4
(395.8)
77 – 80
66.75
66.45
4.58
4.56
3.54
3.46
(39)
C19H15NO3
(305.3)
124 – 125
74.74
74.82
4.95
5.02
4.59
4.70
(62)
C9H9NO3
(179.2)
161 – 164
60.33
60.56
5.06
5.12
7.82
7.94
(64)
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New Compounds
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TABLE I
(Continued)
Calculated/Found
% H
Formula
(M.w.)
M.p., °C
(Yield, %)
Compound
% C
% N
XVIII
XIX
C10H11NO3
(193.2)
182 – 184
62.17
62.12
5.74
5.58
7.25
7.21
(61)
C15H12ClNO4
(305.7)
151 – 155
58.93
58.88
3.96
3.73
4.58
4.42
(42)
XX
C15H13NO3
(255.3)
192 – 195
70.58
70.46
5.13
5.16
5.49
5.42
(64)
XXI
C16H15NO3
(269.3)
150 – 156
71.36
71.45
5.61
5.62
5.20
5.34
(66)
XXII
XXIII
XXIV
XXV
C18H13NO3
(291.5)
169 – 173
74.21
74.18
4.50
4.56
4.81
4.75
(60)
C9H11N3O2
(193.2)
253 – 255
55.95
55.87
5.74
5.86
21.75
21.55
(72)
C9H11N3O2
(193.2)
164 – 165
55.95
55.75
5.74
5.66
21.75
21.86
(69)
C10H13N3O2
(207.2)
215 – 220
57.96
57.88
6.32
6.56
20.28
20.56
(59)
XXVI
XXVII
XXVIII
XXIX
XXX
C15H14ClN3O3
(319.7)
167 – 169
56.35
56.46
4.41
4.56
13.14
13.34
(48)
C15H15N3O2
(269.3)
143 – 145
66.90
66.88
5.61
5.58
15.60
15.46
(56)
C16H17N3O2
(283.3)
172 – 176
67.83
67.88
6.05
6.12
14.83
14.97
(62)
C21H18ClN3O3
(395.8)
167 – 169
63.72
63.67
4.58
4.56
10.62
10.80
(42)
C18H15N3O2
(305.3)
197 – 199
70.81
70.76
4.95
4.90
13.76
13.66
(56)
XXXI
C17H13NO
(247.3)
71 – 72
82.57
82.50
5.30
5.45
5.66
5.44
(32)
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New Compounds
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TABLE III
1H NMR spectra (δ, ppm) of benzo[b]furo[3,2-b]pyrrole derivatives
Compound
H-3
H-arom
R
R1
VIII a
XII b
6.86 d
6.84 s
7.25 – 7.87 m
7.10 – 7.75 m
11.37 bs (NH)
3.86 s (CH3)
3.87 s (OCH3)
4.23 s (OCH3)
XVI c
5.92
(OCH3)
s (CH2), 3.73 s
6.99 s
7.00 – 7.75 m
m (C6H5) in H arom.
5.95 s (CH2)
XXII c
XXX c
XXXI c
6.94 s
6.92 s
6.19 d
7.00 – 7.75 m
7.00 – 7.75 m
7.00 – 7.60 m
not observed
m (C6H5) in H arom.
5.97 s (CH2),
9.54 bs (NH)
4.38 bs (NH2)
6.79 d (H-2)
J(2,3) = 3.1
7.17 m (C6H5)
5.31 s (CH2),
7.26 m (C6H5)
Solvents: a (CD3)2CO; b CDCl3; c (CD3)2SO.
TABLE IV
IR and UV spectra of synthesized compounds
Compound ν(CO), cm−1 λmax (log ε), nm
Compound ν(CO), cm−1 λmax (log ε), nm
V
1 665
1 669
1 676
1 686
1 680
1 675
1 701
1 692
1 698
1 694
1 703
1 694
1 663
1 645
306 (3.53), 251 (2.74)
309 (3.50)
XIX
1 647
1 646
1 645
1 657
1 649
1 628
1 651
1 626
1 634
1 637
1 640
1 622
1 617
–
304 (3.50)
305 (3.52)
306 (3.46)
VI
XX
VII
VIII
IX
307 (3.56)
XXI
322 (3.67), 258 (3.18)
307 (3.48)
XXII
XXIII
XXIV
XXV
320 (3.55), 263 (3.12)
307 (3.45), 232 (2.84)
303 (3.48)
X
310 (3.52)
XI
303 (3.58), 255 (2.87)
323 (3.65), 263 (3.15)
308 (3.50)
306 (3.62), 232 (3.03)
XII
XIII
XIV
XV
XVI
XVII
XVIII
XXVI
XXVII
XXVIII
XXIX
XXX
304 (3.45)
311 (3.48)
307 (3.47)
309 (3.58), 256 (2.98)
324 (3.55), 263 (3.07)
302 (3.44)
306 (3.56)
305 (3.41)
316 (3.41), 253 (3.08)
298 (3.12)
306 (3.49)
XXXI
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Krutosikova, Dandarova, Bobosik:
Methyl 2-R-3-R1-4H-Furo[3,2-b]pyrrole-5-carboxylates (V – VII)
Methyl 2-azido-3-(R, R1-substituted-2-furyl)propenoate (1 g) was dissolved in toluene (100 ml). The
mixture was refluxed under stirring for 1 h, the solvent was evaporated in vacuo and the product was
crystallized from methanol. Starting from IV analogously was prepared methyl 1H-benzo[b]furo-
[3,2-b]pyrrole-2-carboxylate (VIII).
Methyl 2-R-3-R1-4-Methylfuro[3,2-b]pyrrole-5-carboxylates (IX – XII)
A solution of sodium hydroxide (50%, 30 ml), methyl iodide (1.56 g, 11 mmol) and triethylbenzyl-
ammonium chloride (0.4 g) were added to a stirred solution of esters IIa – IId (10 mmol) in toluene
(100 ml). The temperature was then raised to 65 °C and the mixture stirred for 4 h, diluted with
water and the organic layer was separated. The aqueous layer was extracted with ether and combined
with toluene solution, dried with sodium sulfate and the solvent was removed. The residue was crys-
tallized from ethanol. Starting from VIII was made methyl 1-methylbenzo[b]furo[3,2-b]pyrrole-2-
carboxylate (XII).
Methyl 2-R-3-R1-4-Benzylfuro[3,2-b]pyrrole-5-carboxylates (XIII – XV)
A solution of sodium hydroxide (50%, 30 ml) and benzyl chloride (1.75 ml, 21 mmol) were added
to stirred solution of the compounds Ia – Id (17 mmol) in toluene (30 ml). Finally triethylbenzyl-
ammonium chloride (1.2 g) was added and the mixture was kept stirred at 60 °C for 4 h. The cooled
organic layer was separated, the aqueous one was three times extracted with toluene, the collected
toluene layers were washed with water and dried with sodium sulfate. The product was crystallized
after toluene has been distilled off under reduced pressure.
By the same way was prepared methyl- and benzylbenzo[b]furo[3,2-b]pyrrole-5-carboxylate (XVI).
2-R-3-R1-4-R2-Furo[3,2-b]pyrrole-5-carboxylic Acids (XVII – XXI)
Esters IX – XI, XIII – XV (0.01 mol) in ethanol (50 ml) and 5% sodium hydroxide (20 ml) were
heated on steam bath for 1 h and concentrated to half of its original volume. The precipitate was
dissolved in dilute ethanol (50%), acidified with hydrochloric acid 1 : 1 and poured into ice. The
precipitate was filtered off and crystallized from methanol. Analogously was prepared 1-benzyl-
benzo[b]furo[3,2-b]pyrrole-2-carboxylic acid (XXII) from XVI.
2-R-3-R1-4-R2-Furo[3,2-b]pyrrole-5-carbohydrazides (XXIII – XXIX)
Hydrazine hydrate (88%, 3.5 g) was added to a solution of corresponding esters (10 mmol) in ethanol
(60 ml). The mixture was refluxed for 20 h, cooled and separated precipitate was filtered off. The
compounds XXIII – XXIX were crystallized from ethanol. Analogously was prepared 1-benzyl-
benzo[b]furo[3,2-b]pyrrole-2-carbohydrazide (XXX).
1-Benzylbenzo[b]furo[3,2-b]pyrrole (XXXI)
A solution of 1-acetylbenzo[b]furo[3,2-b]pyrrole (1.99 g, 0.01 mol) in ethanol (25 ml) was refluxed
with sodium hydroxide (5%, 15 ml) for 20 min and poured on ice. Extraction with ether, washing the
extract with 0.1 M hydrochloric acid and water drying over sodium sulfate and evaporation of solvent
afforded XXXI.
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This study was supported by Grant Agency of Slovak Ministry of Education (Registr. No. 1/141/92).
Authors are indebted to Mrs S. Markusova and Dr M. Hrobonova for measurement of IR and UV
spectra. The excellent assistance of Mrs J. Lehka is gratefully acknowledged.
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