Reaction of 1,3-dicarbonyl compounds with o-phenylenediamine or 3,3′-diaminobenzidine in water or under solvent-free conditions via microwave irradiation

Article abstract of DOI:10.1002/jhet.5570420540

Reaction of o-phenylenediamine with β-diketones or β-ketoesters in water formed 2-substituted benzimidazoles. Reaction of 3,3′- diaminobenzidine gave similar results. Under microwave irradiation conditions solvent-free reaction of o-phenylenediamine with β-ketoesters afforded 1,5-benzodiazepin-2-one derivatives. An exception is the reaction of o-phenylenediamine with ethyl acetoacetate under microwave irradiation, which gave 2-methylbenzimidazole.

Full text of DOI:10.1002/jhet.5570420540

Jul-Aug 2005
Reaction of 1,3-Dicarbonyl Compounds with o-Phenylenediamine or
1001
3
,3'-Diaminobenzidine in Water or under Solvent-free Conditions via
Microwave Irradiation
Zhong-Xia Wang* and Hua-Li Qin
Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China.
Received December 16, 2004
Reaction of o-phenylenediamine with β-diketones or β-ketoesters in water formed 2-substituted benzimi-
dazoles. Reaction of 3,3'-diaminobenzidine gave similar results. Under microwave irradiation conditions
solvent-free reaction of o-phenylenediamine with β-ketoesters afforded 1,5-benzodiazepin-2-one deriva-
tives. An exception is the reaction of o-phenylenediamine with ethyl acetoacetate under microwave irradia-
tion, which gave 2-methylbenzimidazole.
J. Heterocyclic Chem., 42, 1001 (2005).
Scheme 1
Synthesis of heterocyclic compounds in aqueous media
and under solvent-free conditions using microwave irradi-
ation has been studied extensively [1-5]. In aqueous media
a number of organic reactions proceed more rapidly and
efficiently than in organic solvents. Some of the reactions
show also different regio- or diasteroselectivity when car-
ried out in water instead of in the usual organic solvents [6-
Condensation of 1,3-dicarbonyl compounds and o-phenylenediamine in water
9
]. For example, reaction of alkynes with azides in hot
water yields 1,2,3-triazole derivatives regioselectively
10]. Microwave irradiation provides unique chemical
[
processes with special attributes such as enhanced reaction
rates, higher yields, greater selectivity and the ease of
manipulation [5].
Benzimidazoles and 1,5-benzodiazepin-2-ones are of
potential biological interest. Benzimidazoles have been
widely used in medicinal chemistry [11,12]. Their synthe-
sis was also extensively explored, including use of some
green synthetic methods [13-15]. 1,5-Benzodiazepin-2-
one derivatives are of pharmacological activity [16,17].
However, studies on their synthesis are relatively rare [17-
Scheme 2
Condensation of 1,3-dicarbonyl compounds and 3,3'-diaminobenzidine in water
2
1]. Here we report our investigation on reactions of 1,3-
dicarbonyl compounds with o-phenylenediamine or 3,3'-
diaminobenzidine in aqueous media or under solvent-free
conditions using microwave irradiation and synthesis of
benzimidazole and 1,5-benzodiazepin-2-one derivatives.
Reaction of o-phenylenediamine with 2,4-pentanedione
or methyl pivaloylacetate in distilled water under reflux
conditions afforded 2-alkylbenzimidazoles 1 and 2,
respectively (Scheme 1). Reaction of o-phenylenediamine
with 2-acylcyclohexanones or 2-cycloalkanonecarboxy-
late gave benzimidazole derivatives 3-6 (Scheme 1) in
excellent yields. The reactions are chemoselective. In each
reaction only the carbonyl of the cycloalkanone acts with
the amino groups of o-phenylenediamine. The reaction of
3
,3'-diaminobenzidine with the β-diketones or β-
ketoesters was similar giving compounds 7-10 (Scheme 2).
It is noteworthy that the reaction of 3,3'-diaminobenzidine
must be carried out under nitrogen. If the reaction was per-
formed in air, a mixture was obtained. This may be
because 3,3'-diaminobenzidine is more air-sensitive than

1
002
Z.-X. Wang and H.-L. Qin
Vol. 42
o-phenylenediamine. All products were solid and isolated
by simple filtration. The products have good purity shown
1
by their respective H NMR spectra. However, the samples
for elemental analyses and melting points determination
were recrystallized from appropriate solvents (see experi-
mental section).
Solvent-free reaction of o-phenylenediamine with β-
ketoesters under microwave irradiation are summerized in
Scheme 3. Reaction of o-phenylenediamine with
t
RC(O)CH COOMe (R = Bu or Ph) afforded 1,5-benzodi-
2
azepin-2-one derivatives 11 and 12, respectively. Similar
reaction with methyl cyclohexanonecarboxylate produced
corresponding 1,5-benzodiazepin-2-one derivative 13,
while with methyl cyclopentanonecarboxylate afforded
1
13
compound 14. Their H and C NMR spectra showed that
compounds 11-13 exist in the imine forms, while 14 in the
enamine form [22,23]. Which forms the 1,5-benzodiazepin-
2-one derivatives exist in depend on the skeletal structure
of the compounds and the properties of the substituted
groups. For example, compounds 14 and A exist in the
enamine forms [24], while the compound B exists in the
imine form [25]; compound 13 exists in an imine form,
while
compound C exists in the enamine form [22]. In addi-
tion, compound 14 can also be transformed to the imine
form during the reaction shown in eq. 1 [26].
Scheme 3
Solvent-free reactions of o-phenylenediamine with β-ketoesters under
microwave irradiation
A mixture of o-phenylenediamine and ethyl acetoac-
etate was irradiated with microwave (300 W) for 3 min
to form 15 (Scheme 4) in 96% yield. Compound 15 was
further irradiated with microwave (700 W) for 4 min to
yield 2-methylbenzimidazole in 95% yield. If a mixture
of o-phenylenediamine and ethyl acetoacetate was irra-
diated with microwave (700 W) for 7 min, 2-methylben-
zimidazole was obtained. Hence, compound 15 is an
intermediate in the formation of 2-methylbenzimidazole
from o-phenylenediamine and ethyl acetoacetate under
microwave irradiation. The reactivity difference
between ethyl acetoacetate and other β-ketoesters
1
RC(O)CH CO R may be caused by the steric hinder-
2
2
ance of R groups. Soufiaoui and co-workers reported
28] that the reaction of o-phenylenediamine with ethyl
acetoacetate in xylene under microwave irradiation gave
-methyl-1H-1,5-benzodiazepin-2(3H)-one in 83%
[
4
yield. This shows that reaction media affect the reaction
significantly.

Jul-Aug 2005
Reaction of 1,3-Dicarbonyl Compounds with o-Phenylenediamine
1003
Scheme 4
distilled water (20 ml) formed white solid product 2 (1.29 g,
1
Solvent-free reaction of o-phenylenediamine with ethyl acetoacetate
75%). 2 was recrystallized from EtOH, m.p. 237.5-238.5 °C. H
t
under microwave irradiation
NMR (DMSO-d ): δ 1.40 (s, 9H, Bu ), 7.10-7.12 (m, 2H, C H ),
6
6 4
7
1
1
.40 (d, J = 7 Hz, 1H, C H ), 7.53 (d, J = 6.8 Hz, 1H, C H ),
6 4 6 4
1
3
2.06 (s, 1H, NH). C NMR (DMSO-d ): δ 29.70, 33.61,
11.20, 118.75, 121.16, 121.86, 135.08, 143.24, 162.61. IR
6
(
KBr): 3065w, 3051w, 2967s, 2921m, 2872m, 2773m, 2677m,
1
1
621vw, 1590vw, 1532w, 1451s, 1407vs, 1362m, 1308m, 1275s,
−1
219m, 1180w, 1013m, 992m, 748m, 734m cm
-(1H-Benzo[d]imidazol-2-yl)heptan-2-one (3).
Reaction between o-phenylenediamine (1.06 g, 9.80 mmol)
.
7
and 2-acetylcyclohexanone (1.40 g, 10.06 mmol) in distilled
water (20 ml) gaved pale yellow solid 3 (2.12g, 94%). 2 was
1
recrystallized from CH COOEt, m.p. 95.5-96.5°C. H NMR
3
(
CDCl ): δ 1.23-1.33 (m, 2H, CH ), 1.45-1.55 (m, 2H, CH ),
3 2 2
1
.76-1.86 (m, 2H, CH ), 2.03 (s, 3H, Me), 2.33 (t, J = 7 Hz, 2H,
2
CH ), 2.95 (t, J = 7.3 Hz, 2H, CH ), 7.17-7.20 (m, 2H, C H ),
2
2
6 4
1
3
7
2
2
2
1
1
.51-7.54 (m, 2H, C H ). C NMR (CDCl ): δ 22.98, 27.97,
6 4 3
8.26, 28.48, 29.99, 43.22, 114.50, 123.15, 136.71, 155.02,
09.29. IR (KBr): 3173m, 3123m, 3107m, 3044m, 3029m,
934s, 2889m, 2863s, 2784m, 2636m, 2612m, 1712vs, 1623m,
In addition, reaction of o-phenylenediamine with β-
diketones under solvent-free conditions via MW radiation
was also tried. However, each reaction gave a mixture.
534m, 1456s, 1437m, 1412s, 1367m, 1274s, 1223w, 1158m,
−1
014w, 771m cm
.
Anal. Calcd. for C14H18N O: C, 73.01, H, 7.88, N, 12.16.
2
Found: C, 73.14, H, 8.02, N, 12.35.
EXPERIMENTAL
6
-(1H-Benzo[d]imidazol-2-yl)-1-phenylhexan-1-one (4).
Reaction of o-phenylenediamine (1.06 g, 9.80 mmol) and 2-
benzoylcyclohexanone (2.02 g, 9.89 mmol) in distilled water (20
Reactions using o-phenylenediamine as starting material were
performed in air, while reactions of 3,3'-diaminobenzidine were
ml) afforded pale yellow solid 4 (2.72g, 95%). 4 was recrystal-
1
13
carried out under nitrogen. H and C NMR spectra were
recorded on a Bruker av300 or Bruker av400 spectrometer and
the chemical shifts are referenced to internal solvent resonances.
IR spectra were recorded on a Bruker VECTOR-22 spectrometer.
MW reactions were carried out using an unmodified Sanyo EM-
1
lized from CH COOEt, m.p. 140-141°C. H NMR (CDCl ): δ
3
3
1
2
7
13
.32-1.43 (m, 2H, CH ), 1.64-1.73 (m, 2H, CH ), 1.74-1.86 (m,
2 2
H, CH ), 2.85-2.92 (m, 4H, CH ), 7.11-7.14 (m, 2H, H ), 7.35-
2
2
ar
.40 (m, 2H, H ), 7.46-7.50 (m, 3H, H ), 7.84-7.88 (m, 2H, H ).
ar
ar
ar
C NMR (CDCl ): δ 23.41, 27.98, 28.59, 28.75, 38.23, 114.75,
3
2
02ES1 household microwave oven. Elemental analyses were
performed by the Analytical Center of University of Science and
Technology of China.
1
1
2
22.21, 127.47, 128.16, 128.73, 128.89, 132.12, 133.26, 136.97,
38.60, 155.15, 200.95. IR (KBr): 3086m, 3055s, 2943vs, 2899s,
863s, 2769s, 2741s, 2681s, 2640s, 2525m, 1685vs, 1676vs,
2
-Methyl-1H-benzimidazole (1).
1622m, 1596m, 1539m, 1503m, 1484m, 1447vs, 1423vs, 1368m,
−1
1
326s, 1271vs, 1212s, 1179w, 1025m, 749vs, 690vs cm
Anal. Calcd. for C19H20N O: C, 78.05, H, 6.89, N, 9.58.
.
A mixture of o-phenylenediamine (1.06 g, 9.80 mmol), 2,4-
2
pentanedione (1.02 g, 10.2 mmol) and distilled water (20 ml) was
refluxed for 5 h. with stirring. The mixture was cooled to room
temperature and filtered. The white solid was washed with dis-
Found: C, 77.93, H, 6.76, N, 9.52.
Methyl 6-(1H-Benzo[d]imidazol-2-yl)hexanoate (5).
tilled water and dried in air to give 1 (1.18 g, 91%). 1 was recrys-
Reaction of o-phenylenediamine (1.06 g, 9.80 mmol) and
methyl 2-oxocyclohexanecarboxylate (1.55 g, 9.92 mmol) in dis-
1
tallized from EtOH, m.p. 176-177 °C (lit.[14] 177-178°C).
H
NMR (CDCl ): δ 2.57 (s, 3H, Me), 7.12-7.19 (m, 2H, C H ),
3
6 4
tilled water (20 ml) afforded pale yellow solid 5 (2.26 g, 94%). 4
7
2
1
1
.44-7.50 (m, 2H, C H ). IR (KBr): 3093w, 3062m, 2994m,
6 4
1
was recrystallized from CH COOEt, m.p. 116.5-118.5°C.
H
3
906m, 2877m, 2847m, 2784m, 2719m, 2677m, 1622m, 1589w,
556s, 1487w, 1450vs, 1421vs, 1386s, 1360m, 1271vs, 1219m,
NMR (CDCl ): δ 1.32-1.40 (m, 2H, CH ), 1.56-1.65 (m, 2H,
CH ), 1.75-1.84 (m, 2H, CH ), 2.26 (t, J = 7 Hz, 2H, CH ), 2.86
3
2
2
2
2
−1
027m, 1003w, 896w, 834m, 737s cm
Similar reaction between o-phenylenediamine (1.06 g, 9.80
mmol) and ethyl acetoacetate (1.30 g, 9.99 mmol) afforded 1
.
(
t, J = 7.3 Hz, 2H, CH ), 3.60 (s, 3H, Me), 7.13-7.16 (m, 2H,
2
1
3
C H ), 7.45-7.49 (m, 2H, C H ). C NMR (CDCl ): δ 24.35,
6
4
6
4
3
2
1
2
1
1
7.88, 28.60, 28.92, 33.78, 51.61, 114.72, 122.28, 138.21,
55.14, 174.40. IR (KBr): 3166w, 3089m, 3050m, 3029m,
993m, 2938m, 2928m, 2866m, 2772m, 2647m, 1739vs, 1623m,
592w, 15401m, 1456s, 1439s, 1419s, 1366m, 1336w, 1308w,
(
1.16 g, 89%).
The reactions of other β-diketones or β-ketoesters with o-
phenylenediamine followed the same procedures and compounds
2
-6 were obtained.
−1
273m, 1190m, 1165s, 1086w, 1018w, 999w, 748s cm
.
2
-t-Butyl-1H-benzimidazole (2) [14].
Reaction between o-phenylenediamine (1.06 g, 9.80 mmol)
Anal. Calcd. for C14H18N2O2: C, 68.27, H, 7.37, N, 11.37.
Found: C, 68.29, H, 7.35, N, 11.46.
and methyl 4,4-dimethyl-3-oxopentanoate (1.58 g, 9.98 mmol) in
Ethyl 5-(1H-Benzo[d]imidazol-2-yl)pentanoate (6)

1
2
004
Z.-X. Wang and H.-L. Qin
Vol. 42
Reaction of o-phenylenediamine (1.06g, 9.80mmol) and ethyl
-oxocyclopentanecarboxylate (1.55g, 9.92mmol) in distilled
28.323, 28.55, 37.82, 127.90, 128.33, 128.72, 129.02, 133.06,
136.77, 148.26, 200.11. IR (KBr): 3058s, 2933s, 2859s, 1678vs,
1627m, 1597m, 1578m, 1530m, 1482m, 1449vs, 1412s, 1280s,
water (20ml) afforded pale yellow solid 6 (2.37g, 98%). 6 was
recrystallized from CH COOEt, m.p. 139-140°C (lit. [22] 138-
1216m, 1178w, 1073w, 1024w, 1003w, 863w, 806m, 750w, 691s
3
1
−1
1
1
40°C). H NMR (CDCl ): δ 1.19 (t, J = 7.1 Hz, 3H, Me), 1.65-
cm
.
3
.72 (m, 2H, CH ), 1.80-1.87 (m, 2H, CH ), 2.32 (t, J = 7 Hz, 2H,
Anal. Calcd. for C38H38N O : C, 78.32, H, 6.57, N, 9.61.
2
2
4 2
CH ), 2.89 (t, J = 7.2 Hz, 2H, CH ), 4.08 (q, J = 7.1 Hz, 2H,
Found: C, 78.41, H, 6.51, N, 9.72.
2
2
1
3
CH ), 7.13-7.17 (m, 2H, C H ), 7.46-7.50 (m, 2H, C H ).
C
2
6
4
6 4
Methyl 6-[2'-(5-Methoxycarbonylpentyl)-1H,1'H-5,5'-bibenzim-
idazolyl-2-yl]hexanoate (10).
NMR (CDCl ): δ 14.23, 24.34, 27.51, 28.86, 33.83, 60.54,
3
1
3
1
1
14.67, 122.14, 136.05, 155.09, 173.89. IR (KBr): 3087w,
052w, 2989m, 2943m, 2916m, 2869m, 2776w, 2734w, 2662w,
727vs, 1622w, 1540w, 1449s, 1422s, 1383m, 1320m, 1270m,
Reaction of 3,3'-diaminobenzidine (0.26 g, 1.213 mmol) with
methyl 2-oxocyclohexanecarboxylate (0.38 g, 2.43 mmol) in dis-
tilled water (20 ml) gave pale yellow solid 10 (0.585 g, 98%). 10
−1
229w, 1173s, 1028m, 931w, 860w, 748m cm
.
1
was recrystallized from acetone/dioxane, m.p. 111.5-113.5°C. H
2
,2'-Dimethyl-1H,1'H-5,5'-bibenzimidazolyl (7) [26].
NMR (DMSO-d ): δ 1.32-1.37 (m, 4H, CH ), 1.54-1.61 (m, 4H,
6
2
A mixture of 3,3'-diaminobenzidine (0.26 g, 1.213 mmol), 2,4-
CH ), 1.76-1.82 (m, 4H, CH ), 2.30 (t, J = 7.3 Hz, 4H, CH ),
2 2 2
pentanedione (0.25 g, 2.497 mmol) and distilled water (20 ml)
was refluxed under nitrogen for 5 h. with stirring. The mixture
was cooled to room temperature and filtered. The white solid was
2
.78-2.84 (m, 4H, CH ), 3.56 (s, 6H, Me), 7.42-7.73 (m, 6H,
2
13
C H ), 12.19 (s, 2H, NH). C NMR (DMSO-d ): δ 24.24, 27.33,
2
1
1
6
3
6
8.17, 28.49, 33.22, 51.26, 109.09, 118.32, 120.96, 135.26,
55.76, 173.46. IR (KBr): 3141s, 3043s, 2947s, 2867s, 1713vs,
631m, 1538m, 1455vs, 1416s, 1374m, 1287s, 1205s, 1180s,
washed with distilled water and dried in air to give 7 (0.315 g,
1
9
9%). 7 was purified by recrystallizing from pyridine. H NMR
(
(
(
(
DMSO-d ): δ 2.50 (s, 6H, CH ), 7.38-7.41 (m, 2H, C H ), 7.48
−1
6
3
6
3
1141w, 1086w, 1037w, 975w, 862m, 814s, 733s cm
.
1
3
d, J = 8.3 Hz, 2H, C H ), 7.64-7.65 (m, 2H, C H ). C NMR
6
3
6
3
Anal. Calcd. for C28H34N O : C, 68.55, H, 6.99, N, 11.42.
4 4
DMSO-d ): δ15.62, 113.09, 115.54, 121.71, 136.02, 152.68. IR
6
Found: C, 68.43, H, 7.01, N, 11.60.
KBr): 3129m, 3062s, 2995s, 2921ws, 2851s, 2795s, 2686m,
4
-tert-Butyl-1,3-dihydro-2H-1,5-benzodiazepin-2-one (11).
A mixture of o-phenylenediamine (1.06 g, 9.80 mmol) and
1
1
7
631m, 1593w, 1582w, 1556m, 1543w, 1452vs, 1403s, 1387s,
352w, 1276s, 1215w, 1130w, 1023s, 986w, 948w, 846m, 797s,
−1
59w, 740vw, 681w cm
.
methyl pivaloylacetate (1.60 g, 9.86 mmol) was irradiated using
microwave at 700 W for 5 min. After cooling to room tempera-
ture, the pale yellow solid was washed with water and then dried
in air to give 11 (1.77 g, 84%). 11 was recrystallized from EtOH,
Similar reaction between 3,3'-diaminobenzidine (0.26 g, 1.213
mmol) and ethyl acetoacetate (0.33 g, 2.53 mmol) formed 7 (0.31
g, 97%).
1
t
m.p. 138-139°C. H NMR (CDCl ): δ 1.31 (s, 9H, Bu ), 3.19 (s,
Compounds 8-10 were prepared similarly.
3
2
7
2
H, CH ), 7.03-7.05 (m, 1H, C H ), 7.15-7.20 (m, 2H, C H ),
2 6 4 6 4
7
2
-[2'-(6-Oxoheptyl)-1H,1'H-5,5'-bibenzimidazolyl-2-yl]heptan-
-one (8).
13
.33-7.35 (m, 1H, C H ), 8.90 (s, 1H, NH). C NMR(CDCl ): δ
6
4
3
7.44, 38.84, 41.34, 121.71, 124.77, 125.99, 128.15, 170.95. IR
Reaction of 3,3'-diaminobenzidine (0.26 g, 1.213 mmol) with
-acetylcyclohexanone (0.35 g, 2.50 mmol) in distilled water (20
(KBr): 3190vs, 3123vs, 3079vs, 2968vs, 2936s, 2892s, 1684vs,
1622s, 1573s, 1482vs, 1425s, 1363vs, 1300m, 1256s, 1227s,
1198m, 1165s, 1118m, 1078s, 1039w, 1025w, 944m, 887w,
831m, 795s, 764vs, 741s, 668m cm−1.
Anal. Calcd. for C13H16N2O: C, 72.19, H, 7.46, N, 12.95.
Found: C, 72.08, H, 7.38, N, 13.01.
Compounds 12-14 were prepared similarly.
2
ml) gave white solid 8 (0.54 g, 96%). 8 was recrystallized from
1
acetone/dioxane, m.p. 101.5-102.5 °C. H NMR (DMSO-d ): δ
6
1
.26-1.29 (m, 4H, CH ), 1.47-1.53 (m, 4H, CH ), 1.74-1.78 (m,
2
2
2
4H, CH ), 2.05 (s, 6H, Me), 2.41 (t, J = 7.3 Hz, 4H, CH ), 2.80
2
2
(
t, J = 7.4 Hz, 4H, CH ), 7.39-7.41 (m, 2H, C H ), 7,50 (s, 2H,
2
6 3
1
3
C H ), 7.66 (s, 2H, C H ), 12.22 (b, 2H, NH). C NMR
6
3
6 3
4
-Phenyl-1,3-dihydro-2H-1,5-benzodiazepin-2-one (12).
(
DMSO-d ): δ 21.63, 27.85, 28.63, 28.90, 30.11, 43.04, 121.28,
6
1
2
1
1
35.53, 156.12, 208.96. IR (KBr): 3187s, 3159s, 3123s, 3058s,
957s, 2934s, 2878s, 2858s, 1702vs, 1627m, 1597w, 1539s,
466s, 1454s, 1414s, 1366m, 1286s, 1222w, 1163m, 1086w,
Reaction of o-phenylenediamine (1.06 g, 9.80 mmol) with
methyl 3-oxo-3-phenylpropanoate (1.78 g, 9.99 mmol) under
MW radiation gave pale yellow solid 12 (2.13g, 92%). 12 was
−1
recrystallized from EtOH, m.p. 205-207°C (lit. [28] 206°C). 1H
019w, 901w, 871m, 806s, 723m, 709m cm
.
Anal. Calcd. for C28H34N O : C, 73.33, H, 7.47, N, 12.22.
NMR (CDCl3): δ 3.52 (s, 2H, CH2), 7.03-7.05 (m, 1H, Har),
4
2
Found: C, 73.18, H, 7.55, N, 11.98.
7.15-7.22 (m, 2H, Har), 7.41-7.46 (m, 4H, Har), 8.03-8.07 (m, 2H,
1
3
H ), 8.39 (s, 1H, NH). C NMR (CDCl ): δ 39.95, 121.86,
ar
3
6
-[2'-(6-Oxo-6-phenylhexyl)-1H,1'H-5,5'-bibenzimidazolyl-2-
1
1
25.30, 126.61, 127.90, 128.86, 129.16, 131.18, 137.85, 140.20,
59.03, 167.63. IR (KBr): 3316vw, 3201m, 3063m, 2975w,
yl]-1-phenylhexan-1-one (9).
Reaction of 3,3'-diaminobenzidine (0.26 g, 1.213 mmol) with
-benzoylcyclohexanone (0.51 g, 2.50 mmol) in distilled water
2911w, 1676vs, 1614m, 1568m, 1474m, 1442m, 1370m, 1311s,
−1
2
1255m, 1018m, 940w, 881w, 755vs cm
.
(
20 ml) gave pale yellow solid 9 (0.68 g, 96%). 8 was recrystal-
1
,2,3,4,10,11a-Hexahydro-1-1H-dibenzo[b,e][1,4]diazepin-11-
1
lized from acetone/dioxane, m.p. 121.5-122.5°C. H NMR
(
1
one (13).
DMSO-d ): δ 1.39-1.43 (m, 4H, CH ), 1.65-1.70 (m, 4H, CH ),
6 2 2
.80-1.84 (m, 4H, CH ), 2.83 (t, J = 6.7 Hz, 4H, CH ), 3.05 (t, J
Reaction of o-phenylenediamine (1.06 g, 9.80 mmol) with
2
2
=
7.0 Hz, 4H, CH ), 7.31-7.74 (m, 12H, H ), 7.90-8.01 (m, 4H,
methyl 2-oxocyclohexanecarboxylate (1.55 g, 9.92 mmol)
under MW radiation gave pale yellow solid 13 (1.94 g, 92%).
2
ar
1
3
H ), 12.23 (s, 2H, NH). C NMR (DMSO-d ): δ 23.55, 27.55,
ar
6

Jul-Aug 2005
Reaction of 1,3-Dicarbonyl Compounds with o-Phenylenediamine
1005
1
1
2
2
3 was recrystallized from EtOH, m.p. 182-183°C (lit. [22]
82-183°C). 1H NMR (CDCl ): δ 2.06 (s, 2H, CH ), 2.27 (s,
We thank the Natural Science Foundation of Anhui Province
for financial support.
3
2
H, CH ), 3.66 (s, 4H, CH ), 3.77 (s, 1H, CH), 6.62-6.68 (m,
2
2
1
3
H, C H ), 6.89-7.00 (m, 2H, C H ), 9.92 (s, 1H, NH).
C
6
4
6 4
REFERENCES AND NOTES
NMR (CDCl ): δ 22.34, 22.92, 23.98, 27.35, 50.75, 115.60,
3
1
1
2
1
8
18.38, 122.38, 122.48, 127.72, 129.24, 143.98, 159.13,
71.48. IR (KBr): 3461s, 3369vs, 3243s, 3065w, 3028w,
984w, 2927s, 2843s, 1638vs, 1580vs, 1505s, 1459s, 1441vs,
313s, 1245vs, 1191s, 1131m, 1079s, 1062m, 983w, 927w,
[
[
1] C.-J. Li, Chem. Rev., 93, 2023 (1993).
2] G. Molteni, A. Ponti and M. Orlandi, New J. Chem., 26, 1340
(
(
2002).
[
3] G. Broggini, G. Molteni and G. Zecchi, Heterocycles, 47, 541
−
1
97vw, 826w, 777m, 743s cm
.
1998).
[
4] A. de la Hoz, A. Díaz-Ortis, A. Moreno and F. Lauga, Eur. J.
Org. Chem., 3659 (2000).
5] Y. Xu and Q.-X. Guo, Heterocycles, 63, 903 (2004).
2
,3,4,9-Tetrahydro-1H-benzo[b]cyclopenta[e][1,4]diazepin-10-
one (14).
[
Reaction of o-phenylenediamine (1.06 g, 9.80 mmol) with
[6] J. W. Wijnen, S. Zavarise and J. B. F. N. Engberts, J. Org.
Chem., 61, 2001 (1996).
ethyl 2-oxocyclopentanecarboxylate (1.55 g, 9.92 mmol) under
MW radiation gave pale yellow solid 14 (1.94 g, 99%). 14 was
recrystallized from EtOH, m.p. 185-187°C (lit. [22] 182-184°C).
[
7] S. Otto, W. Blokzijl and J. B. F. N. Engberts, J. Org. Chem.,
5
9, 5372 (1994).
[
[
8] U. M. Lindström, Chem. Rev., 102, 2751 (2002).
9] J. F. Blake, D. Lim and W. L. Jorgensen, J. Org. Chem., 59,
1
H NMR (CDCl ): δ 1.99-2.11 (m, 2H, CH ), 2.48-2.54 (m, 2H,
3
2
CH ), 2.79-2.85 (m, 2H, CH ), 5.90-5.91 (m, 1H, NH), 6.99-7.10
2
2
803 (1994).
[10] Z.-X. Wang and H.-L. Qin, Chem.Commun., 2450 (2003).
1
3
(
m, 4H, C H ), 8.57 (s, 1H, NH). C NMR (CDCl ): δ 22.38,
6 4 3
3
1
3
1
9
0.63, 32.18, 109.73, 109.94, 121.41, 122.04, 123.69, 128.48,
30.20, 136.05, 154.90. IR (KBr): 3373w, 3182m, 3136s, 3064s,
025s, 2954s, 2900s, 2843s, 2769m, 2707w, 1705vs, 1649s,
624s, 1484vs, 1393vs, 1294m, 1239m, 1188m, 1168m, 1106w,
[11] G. V. Reddy, V. V. V. N. S. R. Rao, B. Narsaiah and P. S. Rao,
Synth. Commun., 32, 2467 (2002), and references therein.
[12] M. P. Singh, S. Sasmal, W. Lu and M. N. Chatterjee,
Synthesis, 1380 (2000).
−1
[13] P. N. Preston, Chem. Rev., 74, 279 (1974).
61w, 888w, 795m, 745s, 731s, 697s, 663s cm
.
[
14] L. M. Dudd, E. Venardou, E. Garcia-Verdugo, P. Licence, A.
Ethyl (2E)-3-[(2-Aminophenyl)amino]but-2-enoate (15).
J. Blake, C. Wilson and M. Poliakoff, Green Chem., 5, 187 (2003).
[
15] C. T. Brain and J. T. Steer, J. Org. Chem., 68, 6814 (2003).
A mixture of o-phenylenediamine (1.06 g, 9.80 mmol) and
ethyl acetoacetate (1.30 g, 9.99 mmol) was irradiated using
microwave at 300 W for 3 min. After cooling to room tempera-
ture, the pale yellow solid was washed with water and then dried
in air to afford 15 (2.08 g, 96%). 15 was recrystallized from
[
16] H. Abdel-Ghany, A. M. El-Sayed, A. Khodairy and H. Salah,
Synth. Commun., 31, 2523 (2001).
17] M. H. Rao, A. P. R. Reddy and V. Veeranagaiah, Synthesis,
446 (1992).
[18] M. Hamdi, O. Grech, R. Sakellariou and V. Spéziale, J.
Heterocyclic Chem., 31, 509 (1994).
[
1
hexane, m.p. 58-61°C (lit. [29] 59-62°C). H NMR (CDCl ): δ
3
[
[
19] T.-H. Chuang and K. B. Sharpless, Org. Lett., 2, 3555 (2000).
20] M. J. Fray, K. Cooper, M. J. Parry, K. Richardson and J.
1
4
2
.22 (t, J = 7.1 Hz, 3H, Me), 1.73 (s, 3H, Me), 3.75 (s, 2H, NH ),
2
.08 (q, J = 7.1 Hz, 2H, CH ), 4.65 (s, 1H, CH), 6.61-6.69 (m,
2
Steelet, J. Med. Chem., 38, 3514 (1995).
21] R. Achour, M. Z. Cherkaoui, E. M. Essassi and R. Zniber,
Synth. Commun., 24, 2899 (1994).
22] A. Rossi, A. Hunger, J. Kebrle and K. Hoffmann, Helv. Chim.
H, C H ), 6.91 (d, J = 7.6 Hz, 1H, C H ), 6.97-7.03 (m, 1H,
6
4
6 4
[
1
3
C H ), 9.63 (s, 1H, NH). C NMR (CDCl ): δ 14.89, 19.78,
6
4
3
5
1
3
1
1
7
8.88, 85.24, 114.53, 116.88, 120.39, 122.18, 138.77, 151.74,
61.76, 170.86. IR (KBr): 3451m, 3356m, 3246w, 3183vw,
067w, 2984m, 2920w, 2872w, 2850w, 2789w, 2727w, 2679w,
648vs, 1622vs, 1597vs, 1511m, 1485s, 1451m, 1434m, 1385m,
360m, 1271vs, 1219m, 1169vs, 1057s, 1025s, 983w, 834w,
[
Acta, 43, 1298 (1960).
[23] A. Rossi, A. Hunger, J. Kebrle and K. Hoffmann, Helv. Chim.
Acta, 43, 1046 (1960).
[
24] J. B. Press, C. M. Hofmann, N. H. Eudy, W. J. Fanshawe, I. P.
Day, E. N. Greenblatt, S. R. Safir, J. Med. Chem., 22, 725 (1979).
25] A. Mule, G. Pirisino, M. D. Moretti, F. Savelli, A. Boido, M.
−1
85s, 753s, 737s cm
.
[
Transformation of 15 to 2-Methyl-1H-benzimidazole (1) via MW
radiation.
Satta, A. Peana, Boll. Chim. Farm., 133, 167 (1994).
[26] A. Aatif, A. Baouid, A. Benharref, A. Hasnaoui, Synth.
Commun., 30, 2647 (2000).
Ethyl (2E)-3-[(2-aminophenyl)amino]but-2-enoate (15) (1.0 g,
[27] J. Schoenleber, P. L. et J. Néel, Bull. Soc. Chim. Fr., 1926 (1969).
4.54 mmol) was irradiated using microwave at 700 W for 4 min.
[
28] K. Bougrin, A. K. Bennani, S. F. Tétouani and M. Soufiaoui,
After cooling to room temperature, the solid was washed with
Tetrahedron Lett., 35, 8373 (1994).
water and then dried in air to give white solid 1 (0.57g, 95%).
[29] W. A. Sexton, J. Chem. Soc., 303 (1942).