Condensed diazepines. synthesis of 1-aryl-3,5-dihydro-4H-1-benzofuro-[2,3- d][1,2]diazepin-4-ones

Article abstract of DOI:10.1007/s10593-010-0637-4

The cyclocondensation of (2-aroyl-1-benzofuran-3-yl)acetic acids and their methyl esters with hydrazine hydrate under various experimental conditions has been studied. Optimal conditions have been found for obtaining 1-aryl-3,5-dihydro-4H-1-benzofuro[2,3-

Full text of DOI:10.1007/s10593-010-0637-4

Chemistry of Heterocyclic Compounds, Vol. 46, No. 9, 2010
CONDENSED DIAZEPINES. SYNTHESIS OF
1-ARYL-3,5-DIHYDRO-4H-1-BENZOFURO-
[2,3-d][1,2]DIAZEPIN-4-ONES
A. B. Eresko1, V. S. Tolkunov1, and S. V. Tolkunov1*
The cyclocondensation of (2-aroyl-1-benzofuran-3-yl)acetic acids and their methyl esters with hydrazine
hydrate under various experimental conditions has been studied. Optimal conditions have been found
for obtaining 1-aryl-3,5-dihydro-4H-1-benzofuro[2,3-d][1,2]diazepin-4-ones.
Keywords: (2-aroyl-1-benzofuran-3-yl)-acetic acids, 1-aryl-3,5-dihydro-4H-1-benzofuro[2,3-d][1,2]diazepin-
4-ones, hydrazine hydrate, condensed diazepines, polyphosphoric acid, benzoylation, cyclization.
1-Aryl-3,5-dihydro-4H-2,3-benzodiazepin-4-ones are actively studied in connection with the anticonvulsive
activity detected in them [1-4]. Known routes to obtain them are based on the interaction of 2-aroyl-
4,5-dimethoxyphenylacetic acids or their esters with hydrazine [1-6]. Of the heterocyclic analogs of 2,3-benzo-
diazepin-4-ones only 3H-[1,2]diazepino[5,6-b]indoles, obtained by the cyclocondensation of the ethyl ester of
[2-formyl(acetyl)indol-2-yl]acetic acid with hydrazine hydrate are known [7-9]. Similar conversions have not been
described in the 1-benzofuran series. As was shown in our preliminary publication [10], heterocyclization of
hydrazones of (2-acyl-1-benzofuran-3-yl)acetic acid leads to the corresponding azine, but heterocyclization of
hydrazones of arylamides of (2-acetyl-1-benzofuran-3-yl)acetic acid, depending on the conditions, takes place with
the formation of 2-amino-1-methyl-1-benzofuro[2,3-c]pyridin-3-one or azines of arylamides of (2-acetyl-1-
benzofuran-3-yl)acetic acid.
In the present work the reaction of methyl esters of (2-aroyl-1-benzofuran-3-yl)acetic acids 2a-g and
(2-aroyl-1-benzofuran-3-yl)acetic acids 4a-c with hydrazine hydrate has been investigated. The initial esters
2a-g were obtained by acylation of the methyl ester of (6-methyl-1-benzofuran-3-yl)acetic acid (1) with
aroyl(heteroyl) chlorides in the presence of aluminum chloride.
Acylation of methyl ester 1 with benzoic, veratric, and thiophene-2-carboxylic acids in polyphosphoric
acid (PPA) leads to 7-methyl-1-phenyl-3H-pyrano[3,4-b][1]benzofuran-3-one (3a), 7-methyl-1-(thien-2-yl)-3H-py-
rano[3,4-b][1]benzofuran-3-one (3b), and 1-(3,4-dimethoxyphenyl)-7-methyl-3H-pyrano[3,4-b][1]benzofuran-
3-one (3c), from which (2-aroyl-1-benzofuran-3-yl)acetic acids 4a-c were obtained by alkaline hydrolysis.
_______
* To whom correspondence should be addressed, e-mail: s_tolkunov@yahoo.com
1L. M. Litvinenko Institute of Physical-Organic Chemistry and Coal Chemistry, National Academy of Sciences
of Ukraine, Donetsk 83114, Ukraine.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1397-1403, September, 2010.
Original article submitted May 29, 2009.
0009-3122/10/4609-1127©2010 Springer Science+Business Media, Inc.
1127

Only on using veratric acid was a high yield of pyrone 3 (85%) obtained. In the remaining cases this method
gives poor yields and substances were purified with difficulty, consequently we did not use it in the synthesis of
other derivatives.
CO2Me
CO2Me
O
RCOCl
AlCl3
Me
O
Me
O
R
1
2a–g
RCO2H
PPA
CO2H
O
O
NaOH
HCl
O
Me
O
Me
O
R
R
3a–с
4a–с
2 a R = Ph, b R = 2-thienyl, c R = 3-МеOС6Н4, d R = 2-МеOС6Н4, e R = 4-ClС6Н4,
f R =4-MeС6Н4, g R = 2-ClС6Н4; 3, 4 a R = Ph, b R = 2-thienyl, с R = 3,4-(МеО)2С6Н3
The heterocyclization of (2-aroyl-6-methyl-1-benzofuran-3-yl)acetic acids 4a-c proceeded readily on
extended boiling (20 h) with a fivefold quantity of hydrazine hydrate in ethyl cellosolve in the presence of
catalytic amounts of acetic acid (method A). 1-Aryl-8-methyl-3,5-dihydro-4H-1-benzofuro[2,3-d][1,2]diazepin-
4-ones 5a,b,h were obtained in yields up to 50%. Under analogous conditions the heterocyclization of the
methyl esters of (2-aroyl-1-benzofuran-3-yl)acetic acids 2a-g leads to a mixture of the hydrazide-hydrazones
1
and the corresponding diazepines 5a-g with a predominance of the latter (according to data of H NMR
spectroscopy and chromato-mass spectra).
O
O
method B,C
NH
N
N H ,
2-PrOH
2a–g
TsOH
AcOH
Me
2
4
3a–c
Me
5a,b,h
NHNH2
NNH2
O
O
R
method А
method А
5a–g
R
6a–c
5a,b,h
4a–c
5 a R = Ph, b R = 2-thienyl, c R = 3-МеОС6Н4, d R = 2-МеOС6Н4, e R = 4-ClС6Н4,
f R = 4-МеС6Н4, g R = 2-ClС6Н4, h R = 3,4-(МеО)2С6Н3; 6 a R = Ph,
b R =2-thienyl, с R = 3,4-(МеО)2С6Н3
Treatment of the obtained mixture of reaction products with the acetic acid in the presence of catalytic
amounts of p-toluenesulfonic acid enabled the preparation of diazepines 5a-g in 40-60% yield (method B).
Attempts to optimize method B, using keto esters 2a-g, hydrazine hydrate, the acetic acid, and
p-toluenesulfonic acid as catalyst gave better yields of the final diazepines than in the two-stage procedure and
more dirty reaction products. The best results were obtained on heterocyclization of esters 2a-g with a fivefold
quantity of hydrazine acetate in ethyl cellosolve (method C). Boiling keto acids 4a-c in ethyl cellosolve with
hydrazine dihydrochloride did not lead to diazepines.
1128

Pyrones 3a-c in method A were converted into diazepines in up to 40% yield, but on boiling in
2-propanol gave only hydrazide-hydrazones 6a-c, which may be converted into the corresponding diazepines by
boiling in acetic acid with p-toluenesulfonic acid as catalyst.
1
In the H NMR spectra of diazepines 5a-h the signals of the CH2 group protons were displayed in 3.60
region, and of the NH group in 11.0 region ppm. The following were characteristic of the chromato-mass spectra
of compounds 5a and 5f. For 5a retention time was 0.714 min (99.26%), m/z 291.2 ([M + 1]+ calculated 290.11),
for 5f retention time was 0.718 min (98.52%), m/z 305.0 ([M + 1]+ calculated 304.12).
Table 1. Characteristics of the Synthesized Compounds 1-6
Found, %
Calculated, %
——————
Com-
pound
Empirical
formula
Yield, %
mp, °C
(method)
C
H
Cl
N
S
1
C12H12O3
70.41
70.58
74.12
74.01
65.06
64.95
70.85
70.99
70.87
70.99
66.69
66.58
74.39
74.52
66.46
66.58
78.15
78.25
68.18
68.07
71.31
71.42
73.59
73.46
64.09
63.99
67.64
67.79
74.34
74.47
64.70
64.85
71.35
71.24
71.36
71.24
66.69
66.57
75.09
74.98
66.45
66.57
78.42
78.56
67.21
67.07
58.71
58.52
5.84
5.92
5.17
5.23
4.40
4.49
5.44
5.36
5.42
5.36
4.49
4.41
5.70
5.63
4.32
4.41
4.31
4.38
3.50
3.57
4.86
4.79
4.70
4.79
3.95
4.03
5.24
5.12
4.94
4.86
4.00
4.08
5.10
5.03
4.94
5.03
4.11
4.03
5.20
5.30
4.10
4.03
5.25
5.18
5.70
5.63
4.80
4.91
—*
92
76
64
74
80
62
62
66
10
25
85
92
42
90
2a
2b
2c
2d
2e
2f
C19H16O4
117-118
101-103
79-80
C17H14O4S
C20H18O5
10.11
10.20
C20H18O5
81-82
C19H15ClO4
C20H18O4
10.29
10.34
134-136
83-85
2g
3a
3b
3c
4a
4b
4c
5a
5b
5c
5d
5e
5f
C19H15ClO4
C18H12O3
10.27
10.34
79-80
186-187
164-166
194-195
171-172
146-148
189-190
214-216
197-198
203-205
184-186
229-231
210-211
211-212
208-210
191-192
170-171
168-170
C16H10O3S
C20H16O5
11.28
11.36
C18H14O4
C16H12O4S
C20H18O6
10.61
10.68
C18H14N2O2
C16H12N2O2S
C19H16N2O3
C19H16N2O3
C18H13ClN2O
C19H16N2O2
C18H13ClN2O2
C20H18N2O4
C18H18N4O2
C16H16N4O3S
C20H22N4O4
9.57
9.65
9.40
9.45
8.67
8.74
8.81
8.74
8.70
8.63
9.12
9.20
8.59
8.63
7.95
8.00
57 (A),
20 (B)
33 (A),
35 (B)
42 (B),
53 (C)
18 (B),
21 (C)
10.75
10.82
10.81
10.92
63 (B),
61 (C)
43 (B)
20 (C)
40 (A)
46
5g
5h
6a
6b
6c
10.82
10.92
17.30
17.38
9.93
9.76
39
62.71
62.82
5.87
5.80
14.54
14.62
41
_______
*Bp 150oC (9 mm Hg).
1129

TABLE 2. 1H NMR Spectra of Compounds 1-6
Com-
pound
Chemical shifts, δ, ppm (J, Hz)
1
2
1
2.47 (3Н, s, 6-СН3); 3.68 (3H, s, CO2CH3); 3.70 (2H, s, CH2); 7.04 (1Н, d, J = 8.0, H-5);
7.27 (1H, s, H-7); 7.41 (1Н, d, J = 8.0, H-4); 7.66 (1H, s, H-2)
2a
2b
2c
2d
2.53 (3Н, s, 6-СН3); 3.68 (3Н, s, CO2CH3); 4.14 (2H, s, CH2); 7.18 (1H, d, J = 8.0, H-5);
7.42 (1H, s, H-7); 7.54 (2Н, t, J = 8.0, Н-3',5'); 7.62 (2H, m, H-4,4');
8.08 (2Н, d, J = 8.0, Н-2',6')
2.55 (3Н, s, 6-СН3); 3.68 (3Н, s, CO2CH3); 4.19 (2H, s, CH2); 7.18 (1H, d, J = 8.0, H-5);
7.27 (1H, t, J = 4.0, H-4'); 7.46 (1H, s, H-7); 7.61 (1H, d, J = 8.0, H-4);
7.91 (1H, d, J = 4.0, H-5'); 8.39 (1H, d, J = 4.0, H-3')
2.54 (3Н, s, 6-СН3); 3.70 (3Н, s, CO2CH3); 3.90 (3H, s, 3'-OCH3); 4.17 (2H, s, CH2);
7.18 (2H, m, H-5,5'); 7.43 (1H, d, J = 1.6, H-7); 7.45 (1H, dd, J = 8.0, J = 1.6, H-4);
7.56 (1H, d, J = 2.1, H-2'); 7.63 (1H, dd, J = 8.0, J = 2.1, H-4'); 7.70 (1H, d, J = 8.0, H-6')
2.49 (3Н, s, 6-СН3); 3.68 (3Н, s, CO2CH3); 3.76 (3H, s, 2'-OCH3); 4.07 (2H, s, CH2);
7.04 (1H, t, J = 8.0, H-5'); 7.08 (1Н, d, J = 8.0, Н-3'); 7.12 (1H, d, J = 8.0, H-5);
7.27 (1H, s, H-7); 7.35 (1H, d, J = 8.0, H-4); 7.51 (1H, t, J = 8.0, H-4');
7.57 (1H, d, J = 8.0, H-6')
2e
2f
2.54 (3Н, s, 6-СН3); 3.69 (3Н, s, CO2CH3); 4.18 (2H, s, CH2); 7.20 (1H, d, J = 8.0, H-5);
7.42 (1H, s, H-7); 7.56 (2H, d, J = 8.0, Н-3',5'); 7.65 (1H, d, J = 8.0, H-4);
8.11 (2H, d, J = 8.0, H-2',6')
2.46 (3Н, s, 4'-СН3); 2.53 (3Н, s, 6-СН3); 3.68 (3Н, s, CO2CH3); 4.16 (2H, s, CH2);
7.18 (1H, d, J = 8.0, H-5); 7.33 (2H, d, J = 8.0, Н-3',5'); 7.39 (1H, s, H-7);
7.60 (1H, d, J = 8.0, H-4); 7.99 (2H, d, J = 8.0, Н-2',6')
2g
3a
3b
3c
2.48 (3Н, s, 6-СН3); 3.67 (3Н, s, CO2CH3); 4.14 (2H, s, CH2); 7.15 (1H, d, J = 8.0, H-5);
7.29 (1H, s, H-7); 7.42–7.54 (4Н, m, Н-3'–6'); 7.62 (1H, d, J = 8.0, H-4)
2.51 (3Н, s, 7-СН3); 6.69 (1Н, s, H-4); 7.19 (1H, d, J = 8.0, H-6); 7.38 (1Н, s, Н-8);
7.50–7.62 (3H, m, H-3'–5'); 7.95 (1Н, d, J = 8.0, H-5); 8.11 (2H, d, J = 8.0, H-2',6')
2.54 (3Н, s, 7-СН3); 6.50 ( 1Н, s, H-4); 7.16 (1H, d, J = 8.0, H-6); 7.25 (1Н, t, J = 4.0, H-4');
7.31 (1H, s, H-8); 7.73 (1Н, d, J = 4.0, H-5'); 7.85 (2H, m, H-5,3')
2.51 (3Н, s, 7-СН3); 3.89 (3Н, s, 3'-ОСH3); 3.91 (3Н, s, 4'-ОСH3); 6.43 (1Н, s, H-4);
7.01 (1H, d, J = 8.0, H-5'); 7.12 (1H, d, J = 8.0, Н-6); 7.27 (1H, s, H-8);
7.53 (1H, s, H-2'); 7.70 (1Н, d, J = 8.0, Н-6'); 7.82 (1Н, d, J = 8.0, H-5)
4a
4b
4с
2.52 (3Н, s, 6-СН3); 4.08 (2Н, s, СН2); 7.18 (1H, d, J = 8.2, H-5); 7.41 (1Н, s, Н-7);
7.50–7.64 (3H, m, H-3'–5'); 7.66 (1H, d, J = 8.2, H-4); 8.06 (2H, d, J = 8.2, H-2',6');
12.28 (1H, s, СООH)
2.53 (3Н, s, 6-СН3); 4.10 (2H, s, CH2); 7.17 (1H, d, J = 8.0, H-5); 7.26 (1H, t, J = 4.0, H-4');
7.44 (1H, s, H-7); 7.63 (1H, d, J = 8.0, H-4); 7.91 (1H, d, J = 4.0, H-5');
8.37 (1H, d, J = 4.0, H-3'); 12.10 (1H, br. s, СООH)
2.52 (3Н, s, 6-СН3); 3.87 (3Н, s, 3'-ОСH3); 3.90 ( 3Н, s, 4'-ОСH3); 4.11 (2Н, s, СН2);
7.01 (1H, d, J = 8.2, H-5'); 7.12 (1H, d, J = 8.2, H-6'); 7.29 (1H, s, H-2'); 7.41 (1H, s, H-7);
7.68 (1H, d, J = 8.0, H-5); 7.98 (1H, d, J = 8.0, H-4); 12.10 (1H, s, СООH)
5a
5b
2.49 (3Н, s, 8-СН3); 3.66 (2Н, s, СН2); 7.16–7.74 (8H, m, H arom); 11.18 (1H, s, NH)
2.52 (3Н, s, 8-СН3); 3.64 (2Н, s, СН2); 7.10 (1H, t, J = 4.0, H-4'); 7.17 (1H, d, J = 8.0, H-7);
7.38 (1Н, s, H-9); 7.46 (1H, d, J = 4.0, H-5'); 7.65 (1Н, d, J = 4.0, H-3');
7.67 (1H, d, J = 8.0, H-6); 11.08 (1H, s, NH)
5c
5d
5e
2.50 (3Н, s, 8-СН3); 3.65 (2Н, s, СН2); 3.83 (3Н, s, 3'-OCH3); 6.97 (1H, d, J = 8.0, H-4');
7.16 (1H, d, J = 8.0, H-7); 7.28–7.32 (4H, m, H-2',5',6',9); 7.66 (1H, d, J = 8.0, H-6);
11.09 (1H, s, NH)
2.47 (3Н, s, 8-СН3); 3.60 (3Н, s, 2'-OCH3); 3.67 (2Н, s, СН2); 7.00–7.06 (2H, m, H-3',5');
7.12 (1H, d, J = 8.0, H-7); 7.20 (1Н, s, H-9); 7.44 (1H, t, J = 8.0, H-4');
7.51 (1H, d, J = 8.0, H-6'); 7.62 (1H, d, J = 8.0, H-6); 11.06 (1H, s, NH)
2.51 (3Н, s, 8-СН3); 3.67 (2Н, s, СН2); 7.18 (1H, d, J = 8.0, H-7); 7.31 (1Н, s, H-9);
7.44 (2H, d, J = 8.0, H-3',5'); 7.69 (1H, d, J = 8.0, H-6); 7.75 (2H, d, J = 8.0, H-2',6');
11.23 (1H, s, NH)
5f
2.41 (3Н, s, 4'-CH3); 2.48 (3Н, s, 8-СН3); 3.63 (2Н, s, СН2); 7.22 (4Н, m, Н arom);
7.63 (3H, m, Н arom); 11.09 (1H, s, NH)
5g
2.47 (3Н, s, 8-СН3); 3.73 (2Н, s, СН2); 7.15 (1H, d, J = 8.0, H-7); 7.23 (1Н, s, H-9);
7.46 (3H, br. s, H-4'–6'); 7.62 (1H, d, J = 8.0, H-6); 7.67 (1H, d, J = 8.0, H-3');
11.31 (1H, s, NH)
1130

TABLE 2 (continued)
1
2
5h
2.51 (3Н, s, 8-СН3); 3.62 (2Н, s, СН2); 3.83 (3H, s, 3'-OCH3); 3.87 (3H, s, 4'-OCH3);
6.91 (1H, d, J = 8.0, H-5'); 7.17 (1H, d, J = 8.0, H-7); 7.26 (1Н, d, J = 8.0, H-6');
7.32 (1H, s, H-9); 7.35 (1H, s, H-2'); 7.67 (1Н, d, J = 8.0, H-6); 10.95 (1H, s, NH)
6a
6b
2.42 (3Н, s, 6-СН3); 3.60 (2Н, s, СН2); 4.10 (2H, br. s, =NNH2);
6.67 (2H, s, CONHNH2); 7.16–7.70 (8H, m, H arom); 8.90 (1Н, s, NH)
2.55 (3Н, s, 6-СН3); 4.08 (2Н, br. s, =NNH2); 4.19 (2H, s, СН2);
6.66 (2H, s, CONHNH2); 7.18 (1Н, d, J = 8.0, H-5); 7.27 (1H, t, J = 4.0, H-4');
7.46 (1H, s, H-7); 7.61 (1Н, d, J = 8.0, H-4); 7.91 (1Н, d, J = 4.0, H-5');
8.39 (1Н, d, J = 4.0, H-3'); 8.85 (1Н, s, NH)
6c
2.54 (3Н, s, 6-СН3); 3.92 (3H, s, 3'-OCH3); 3.95 (3H, s, 4'-OCH3);
4.00 (2H, br. s, =NNH2); 6.64 (2H, s, CONHNH2); 7.01 (1Н, d, J = 8.0, H-5');
7.17 (1Н, d, J = 8.0, H-5); 7.37 (1Н, s, Н-7); 7.63 (1Н, s, Н-2'); 7.68 (1Н, d, J = 8.0, H-4);
7.85 (1Н, d, J = 8.0, H-6'); 8.97 (1Н, s, NH)
EXPERIMENTAL
1
The H NMR spectra were recorded on a Bruker Avance II 400 instrument in DMSO-d6, internal
standard was TMS. Chromato-mass spectra were obtained on an Agilent 1100 LC/MSD VL spectrometer,
method of ionization was APCI (chemical positive ionization at atmospheric pressure). Parameters of the
chromatographic column were length 50 mm, diameter 4.6 mm, stationary phase ZORBAX SB-C18, solvent
acetonitrile–water, 95:5, 0.1% trifluoroacetic acid, gradient elution, solvent supply rate 3.0 ml/min. The
characteristics of the synthesized compounds are given in Tables 1 and 2.
Methyl Ester of (6-Methyl-1-benzofuran-3-yl)acetic Acid (1). Acetyl chloride (4 g, 50 mmol) was
added with cooling to a solution of (6-methyl-1-benzofuran-3-yl)acetic acid (9.5 g, 50 mmol) in dry methanol
(50 ml). The mixture was allowed to stand for 2 days, poured into 5% NaHCO3 solution (200 ml), and extracted
with chloroform. The solvent was evaporated in vacuum, and the residue distilled in vacuum.
Methyl Ester of (2-Aroyl-1-benzofuran-3-yl)acetic Acids 2a-g (General Method). A solution of ester
1 (1.02 g, 5.0 mmol) in methylene chloride (5 ml) was added to a mixture of aluminum chloride (0.86 g, 6.5
mmol) and the appropriate aroyl chloride (6.0 mmol) in dry methylene chloride (10 ml), and the mixture was
stirred for 3 h at 25-30oC. The reaction mixture was poured onto ice (40 g) with hydrochloric acid (7 ml), and
extracted with methylene chloride. The extract was washed with a dilute solution of salt and with water, dried
over Na2SO4, and evaporated. The residue was recrystallized from 2-propanol.
7-Methyl-1-phenyl-3H-pyrano[3,4-b][1]benzofuran-3-one (3a), 7-Methyl-1-(thien-2-yl)-3H-pyrano-
[3,4-b][1]benzofuran-3-one (3b), 1-(3,4-Dimethoxyphenyl)-7-methyl-3H-pyrano[3,4-b][1]benzofuran-3-one
(3c) (General Method). Ester 1 (6.1 g, 30 mmol) and the appropriate benzoic acid (50 mmol) were added to
PPA, prepared from H3PO4 (22 g) and P2O5 (44 g), and the mixture stirred for 1.5 h at 100oC. The reaction
mixture was poured into water (400 ml), neutralized with K2CO3 to weakly alkaline in the medium (pH 9). The
solid was filtered off and recrystallized from methanol.
(2-Benzoyl-6-methyl-1-benzofuran-3-yl)acetic Acid (4a), [6-Methyl-2-(thiophen-2-ylcarbonyl)-1-
benzo-furan-3-yl]acetic Acid (4b), [2-(3,4-Dimethoxybenzoyl)-6-methyl-1-benzofuran-3-yl]acetic Acid (4c)
(General Method). Compound 3a-c (10 mmol) was added to an aqueous solution (30 ml) containing NaOH (1.0 g,
25 mmol), and the mixture heated to complete solution. The solution was cooled and acidified with formic acid . The
precipitated solid was filtered off, washed with water, dried, and recrystallized from 2-propanol.
1-Aryl(hetaryl)-3,5-dihydro-4H-1-benzofuro[2,3-d][1,2]diazepin-4-ones 5 (General Method). A. A
mixture of the appropriate (2-aroyl-1-benzofuran-3-yl)acetic acid 4a-c or pyrone 3a-c was boiled for 20 h with
hydrazine hydrate (5 mmol) in ethyl cellosolve (10 ml) in the presence of catalytic quantities (3-4 drops) of
acetic acid. The reaction mixture was diluted with water. The precipitated solid was filtered off and washed with
water. The product was recrystallized from 2-propanol.
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B. A mixture of the appropriate ester of (2-aroyl-6-methyl-1-benzofuran-3-yl)acetic acid 2 (1 mmol)
with hydrazine hydrate (5 mmol) in ethyl cellosolve (10 ml) was boiled for 20 h in the presence of catalytic
amounts (3-4 drops) of acetic acid. The reaction mixture was diluted with water. The precipitated solid was
filtered off and washed with water. The dried solid was boiled in acetic acid for 5 h in the presence of catalytic
amounts of p-toluenesulfonic acid. The solvent was removed in vacuum. The residue was triturated with water,
the solid filtered off, and washed with water. The product was recrystallized from 2-propanol.
C. A mixture of the appropriate ester of (2-aroyl-1-benzofuran-3-yl)acetic acid 2 (1 mmol) and
hydrazine acetate (5 mmol) in ethyl cellosolve (10 ml) was boiled for 20 h. The reaction mixture was diluted
with water. The precipitated solid was filtered off, and washed with water. The product was recrystallized from
2-propanol.
Hydrazide-hydrazones of (2-aroyl-1-benzofuran-3-yl)acetic acids 6a -c. A mixture of the appropriate
pyrone 3a-c (1 mmol) was boiled for 20 h with hydrazine hydrate (5 mmol) in 2-propanol (15 ml). The reaction
mixture was diluted with water. The precipitated solid was filtered off and recrystallized from 2-propanol.
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