4-aryl-2-(o-hydroxymethylphenylamino)-4-oxo-z-2-butenoic acids as intermediates in the synthesis of z-2-phenacylidene-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-ones [3]

Full text of DOI:10.1023/A:1023745130546

Chemistry of Heterocyclic Compounds, Vol. 39, No. 2, 2003
o
4-ARYL-2-( -HYDROXYMETHYLPHENYLAMINO)-
Z
4-OXO- -2-BUTENOIC ACIDS AS INTERMEDIATES
Z
IN THE SYNTHESIS OF -2-PHENACYLIDENE-
1,2,3,5-TETRAHYDRO-4,1-BENZOXAZEPIN-3-ONES
A. N. Maslivets, N. S. Kistanova, K. S. Bozdyreva, and O. A. Maslivets
Keywords: o-aminobenzyl alcohol, 4-aryl-2-(o-hydroxymethylphenylamino)-4-oxo-2-butenoic acids,
aroylpyruvic acids, 2-phenacylidene-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-ones.
Andreichikov et al. [1] described a synthesis of 2-phenacylidene-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-
one (1) and 2-p-chlorophenacylidene-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-one (2) by heating aroylpyruvic
acids with o-aminobenzyl alcohol in toluene at reflux for 2 h with 70-76% yields.
We have isolated intermediate 2-(o-hydroxymethylphenylamino)-4-oxo-4-phenyl-butenoic acid (3) and
2-(o-hydroxymethylphenylamino)-4-oxo-4-p-chlorophenyl-Z-2-butenoic acid (4) by carrying out this reaction in
benzene at reflux for 10-15 sec. Acids 3 and 4 smoothly cyclize to the corresponding benzoxazepinones 1 and 2
upon heating in decane at reflux for 4-5 min.
CH2OH
ArCOCH2COCOOH
+
–H2O
NH2
H
COOH
CH2OH
O
Ar
C
C
O
C
O
N
.
–H2O
N
.
.
H
C
C
H
H
.
.
3, 4
.
Ar
O
1, 2
1, 3 Ar = Ph, 2, 4 Ar = p-ClC6H4
Regioselective nucleophilic attack of the amino group of the reagent by the ketonic carbonyl group at
C(2) of the acids probably occurs in the first step of the reaction of o-aminobenzyl alcohol and the aroylpyruvic
acids. Intermediates 3 and 4 exist in the enaminoketone form with an H-chelate intramolecular hydrogen bond
(IHB) between the NH group and carbonyl group at C(4), i.e., in the form of Z-isomers. Upon heating, 3 and 4
undergo regioselective cyclodehydration to give benzoxazepinones 1 and 2, which also exist in the
enaminoketone form with an intramolecular hydrogen bond between the NH group and carbonyl group of the
phenacylidene substituent, i.e., in the form of Z-isomers.
__________________________________________________________________________________________
Perm State University, 614990 Perm, Russia; e-mail: koh@psu.ru. Translated from Khimiya
Geterotsiklicheskikh Soedinenii, No. 2, pp. 302-303, February, 2003. Original article submitted December 27,
2002.
0009-3122/03/3902-0271$25.00©2003 Plenum Publishing Corporation
271

o
Z
A
solution of
2-( -Hydroxymethylphenylamino)-4-oxo-4-phenyl- -2-butenoic Acid (3).
benzoylpyruvic acid (0.01 mol) and o-aminobenzyl alcohol (0.01 mol) in benzene (10 ml) was heated at reflux
for 15 sec and cooled. The precipitate formed was filtered off to give 2.55 g (86%) of compound 3;
mp 103-104°C (dec., from benzene). IR spectrum (vaseline), ν, cm-1: 3200 br (OH, NH in IHB), 1660 (C=O in
1
CO2H), 1605 br (C(4)=O in IHB). H NMR spectrum (400 MHz, DMSO-d6, HMDS as the internal standard),
δ, ppm (J, Hz): 4.56 (2H, s, CH2); 5.48 (1H, br. s, OH); 6.43 (1H, s, CH=); 6.97-7.61 (7H, m, o-C6H4 + C6H3);
7.98 (2H, d, J = 6.91, 2 o-CH in COC6H5); 12.01 (1H, s, NH), 13.70 (1H, br. s, CO2H). Found, %: C 68.72;
H 5.11; N 4.66. C17H15NO4. Calculated, %: C 68.68; H 5.09; N 4.71.
p
o
Z
4- -Chlorophenyl-2-( -hydroxymethylphenylamino)-4-oxo- -2-butenoic Acid (4)
was obtained
analogously in 88% yield (2.92 g); mp 152-153°C (benzene). IR spectrum (vaseline), ν, cm-1: 3310 br, 3120 br
1
(OH, NH in IHB), 1670 (C=O in CO2H), 1610 br (C(4)=O in IHB). H NMR spectrum (400 MHz, DMSO-d6,
HMDS as the internal standard), δ, ppm (J, Hz): 4.55 (2H, s, CH2); 5.41 (1H, br. s, OH); 6.38 (1H, s, CH=);
6.97-7.67 (6H, m, C6H4 + 2 m-CH in COC6H4Cl-p); 7.98 (2H, d, J = 8.85, 2 o-CH in COC6H4Cl-p); 12.01 (1H,
s, NH); 14.00 (1H, br. s, CO2H). Found, %: C 61.59; H 4.33; Cl 10.71; N 4.20. C17H14ClNO4. Calculated, %:
C 61.55; H 4.25; Cl 10.69; N 4.22.
Z
A solution of
-2-Phenacylidene-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-one (1).
3
(0.01 mol) in
decane (5 ml) was heated at reflux for 5 min and cooled. The precipitate formed was filtered off to give 2.32 g
(83%) of compound 1; mp 152-154°C (hexane). IR spectrum (vaseline), ν, cm-1: 3085 br (N(1)H in IHB), 1732
(C(3)=O), 1604 br (COC6H5 in IHB). 1H NMR spectrum (400 MHz, DMSO-d6, HMDS as the internal standard),
δ, ppm (J, Hz): 5.21 (2H, s, CH2); 6.62 (1H, s, CH=); 7.18-7.58 (7H, m, C(6-9)H + C6H3); 7.98 (2H, d, J = 7.00,
2 o-CH in COC6H5); 13.01 (1H, s, NH). Found, %: C 73.09; H 4.77; N 5.12. C17H13NO3. Calculated, %:
C 73.11; H 4.69; N 5.01.
Z
p
was synthesized
-2- -Chlorophenacylidene-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-one (2)
analogously in 84% yield (2.64 g); mp 165-167°C (hexane). IR spectrum (vaseline), ν, cm-1: 3080 br (N(1)H in
1
IHB), 1740 (C(3)=O), 16.08 br (COC6H4Cl-p in IHB). H NMR spectrum (400 MHz, DMSO-d6, HMDS as the
internal standard), δ, ppm (J, Hz): 5.20 (2H, s, CH2); 6.55 (1H, s, CH=); 7.17-7.47 (6H, m, C(6-9)H + 2 m-CH in
COC6H4Cl-p); 7.92 (2H, d, J = 8.58, 2 o-CH in COC6H4Cl-p); 12.99 (1H, s, NH). Found, %: C 65.09; H 3.88;
Cl 11.43; N 4.39. C17H12ClNO3. Calculated, %: C 65.08; H 3.86; Cl 11.30; N 4.46.
This work was carried out with the financial support of the Russian Basic Research Fund (Grants
Nos. 01-03-32641 and 02-03-96411) and the NMR spectra were taken at the Urals NMR Center (Russian Basic
Research Fund Grant No. 00-03-40139).
REFERENCES
1.
Yu. S. Andreichikov, L. A. Voronova, Z. D. Belykh, and A. N. Plaksina, USSR Inventor's Certificate
666799; Byul. Izobr., No. 21 (1979).
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