Cyclic structure of n-methyl- 2-aminobenzoyl- and 2-mercapto- benzoylhydrazones of fatty- aromatic aldehydes

Article abstract of DOI:10.1007/s10593-010-0437-x

It has been shown by ¹H NMR spectroscopic methods that the previously unknown N-methyl-2-amino-benzoyl- and 2-mercaptobenzoylhydrazones of phenylacetic and 3-phenylpropionic aldehydes have cyclic benzo-1,2,4-triazepine and benzo-1,3,4-thiadiaze

Full text of DOI:10.1007/s10593-010-0437-x

Chemistry of Heterocyclic Compounds, Vol. 45, No. 11, 2009
CYCLIC STRUCTURE OF N-METHYL-
2-AMINOBENZOYL- AND 2-MERCAPTO-
BENZOYLHYDRAZONES OF FATTY-
AROMATIC ALDEHYDES
B. V. Chernitsa1, A. Yu. Ershov1*, D. A. Komarova1, S. I. Yakimovich2,
V. V. Pakal'nis2, I. V. Zerova2, I. V. Lagoda3, and V. V. Shamanin1
1
It has been shown by H NMR spectroscopic methods that the previously unknown N-methyl-2-amino-
benzoyl- and 2-mercaptobenzoylhydrazones of phenylacetic and 3-phenylpropionic aldehydes have
cyclic benzo-1,2,4-triazepine and benzo-1,3,4-thiadiazepine structures respectively.
Keywords: benzo-1,3,4-thiadiazepines, benzo-1,3,4-triazepines, N-methyl-2-aminobenzoylhydrazones,
2-mercaptobenzoylhydrazones.
The products of condensation of carbonyl compounds with N-methyl-N′-(2-aminobenzoyl)hydrazine
have a cyclic benzo-1,3,4-triazepine structure [1, 2]. On interacting 2-mercaptobenzoylhydrazine with carbonyl
compounds derivatives of benzo-1,3,4-thiadiazepine are formed [3, 4]. In both cases the formation of cyclic
reaction products assumes the intramolecular nucleophilic addition of NH2 or SH groups of the aromatic ring to
the C=N bond of the hydrazone fragment.
R2
R1
O
R1
N
O
O
R2HC
O
N
N
N
H
R1
NH
R2
NH2
X
XH
XH
B
1
A
2a–d
a, b X = NH, R1 = Me, a R2 = CH2Ph, b R2 = CH2CH2Ph; c, d X = S, R1 = H,
c R2 = CH2Ph, d R2 = CH2CH2Ph
_______
* To whom correspondence should be addressed, e-mail: ershov@hq.macro.ru.
1Institute of Macromolecular Compounds, Russian Academy of Sciences, Saint Petersburg 199004, Russia.
2Saint Petersburg State University, Saint Petersburg 198504, Russia; e-mail: viktoriapakalnis@mail.ru.
3Scientific Research Test Center (Medical and Biological Protection) of the State Research Test Institute of Military
Medicine, Defence Ministry of Russian Federation, Saint Petersburg 195043, Russia; e-mail: lagodai@peterst ar.ru.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1725-1727. Original article
submitted June 30, 2009.
1388
0009-3122/09/4511-1388©2009 Springer Science+Business Media, Inc.

The aim of the present work was to study the structure of N-methyl-N′-(2-aminobenzoyl)hydrazones and
(2-mercaptobenzoyl)hydrazones of phenylacetic and 3-phenylpropionic aldehydes, and also their inclination
towards different variants of cyclization in solution leading to the formation of cyclic forms.
Compounds 2a-d were obtained in 60-85% yield after briefly maintaining hydrazides 1 and the
appropriate aldehyde in aqueous alcoholic solution at 25oC (EXPERIMENTAL).
The cyclic benzo-1,3,4-triazepine (or benzo-1,3,4-thiadiazepine) structure B is without doubt the
1
structure of compounds 2a-d, as may be judged by analysis of the H NMR spectra. The formation of a typical
ABX system was observed in the spectra of compounds 2a,c, being derivatives of phenylacetic aldehyde, caused
by the stereoisomerism of the methylene protons of the benzyl group at 2.8-3.0 ppm (AB portion of the ABX
1
system), and the appearance of the H-2 signal at 4.5 ppm (X part of the ABX system). Furthermore, in the H
NMR spectra of compounds 2a,b two signals of equal intensity were observed at 6.0 and 6.3 ppm for the NH
protons of the benzo-1,3,4-triazepine ring, and signals of NH protons at 5.9 and 9.5 ppm were observed in the
1H NMR spectra of compounds 2c,d indicating the cyclic benzo-1,3,4-thiadiazepine form.
It is known that the phenomenon of ring–chain tautomerism of the A ↔ B type is characteristic of
N-methyl-N′-(2-aminobenzoyl)- and (2-mercaptobenzoyl)hydrazones of carbonyl compounds [4-6]. However in
the case of compounds 2a-d we did not observe even trace amounts of the linear hydrazone form A, which was
checked by plotting the 1H NMR spectra in different solvents and by varying the time parameters.
The obtained data on the cyclic structure of the condensation products of hydrazones of N-methyl-
2-aminobenzoic and -2-mercaptobenzoic acids with phenylacetic and 3-phenylpropionic aldehydes open certain
prospects for predicting condensations with more complex derivatives of carbonyl compounds containing
additional functions, such as with 1,3-dioxo compounds or monosaccharides, which will be the subject of our
future investigations.
EXPERIMENTAL
The 1H NMR spectra were obtained on a Bruker AV 400 (400 MHz) spectrometer in DMSO-d6, internal
standard was HMDS. A check on the progress of reactions and the purity of the obtained compounds was
effected by TLC on Silufol UV 254 plates in the system benzene–acetone, 4:1. The N-methylhydrazide of
2-aminobenzoic acid and the hydrazide of 2-mercaptobenzoic acid were obtained by known procedures [7, 8].
2-R-4-methyl-1,2,3,4-tetrahydro-5H-1,3,4-benzotriazepin-5-ones 2a,b and 2-R-1,2,3,4-tetrahydro-
5H-1,3,4-benzothiadiazepin-5-ones 2c,d. A mixture of the N-methylhydrazide of 2-aminobenzoic acid
(0.01 mol) or 2-mercaptobenzoic acid hydrazide (0.01 mol) and aldehyde (0.015 mol) in methanol (30 ml) and
water (15 ml) was maintained at 25oC for 2 h. The precipitated crystals were filtered off, washed with ether, and
dried.
2-Benzyl-4-methyl-1,2,3,4-tetrahydro-5H-1,3,4-benzotriazepin-5-one (2a). Yield 70%; mp 130-132oC.
1H NMR spectrum, δ, ppm (J, Hz): 2.79; 2.91 (2H, ABX system, JAB = 12.5, CH2Ph); 2.93 (3H, s, CH3N); 4.46
(1H, dd, ABX system, JAX = 6.0, JBX = 4.5, H-2); 5.98 (1H, br. s, NH); 6.31 (1H, br. s, NH); 6.60-7.65 (9H, m,
Ar). Found, %: C 71.95; H 6.36; N 15.63. C16H17N3O. Calculated, %: C 71.89; H 6.41; N 15.72.
4-Methyl-2-(2-phenylethyl)-1,2,3,4-tetrahydro-5H-1,3,4-benzotriazepin-5-one (2b). Yield 75%; mp
146-148oC. 1H NMR spectrum, δ, ppm (J, Hz): 1.80 (2H, m, CH 2CH2Ph); 2.74 (1H, m, CH2CH2Ph); 2.82 (1H, m,
CH2CH2Ph); 3.11 (3H, s, CH3N); 4.18 (1H, dd, J = 5.5, J = 4.0, H-2); 6.04 (1H, br. s, NH); 6.31 (1H, br. s, NH);
6.56-7.63 (9H, m, Ar). Found, %: C 72.63; H 6.77; N 15.05. C17H19N3O. Calculated, %: C 72.57; H 6.81; N 14.94.
1
2-Benzyl-1,2,3,4-tetrahydro-5H-1,3,4-benzothiadiazepin-5-one (2c). Yield 60%; mp 178-180oC. H
NMR spectrum, δ, ppm (J, Hz): 2.83, 3.05 (2H, ABX system, JAB = 13.6, CH2Ph); 4.76 (1H, dd, ABX system,
JAX = 6.5, JBX = 6.0, H-2); 5.90 (1H, br. s, NH); 7.21-7.63 (9H, m, Ar); 9.58 (1H, d, J = 4.0, NHCO). Found, %:
C 66.59; H 5.17; N 10.41. C15H14N2OS. Calculated, %: C 66.64; H 5.22; N 10.36.
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2-(2-Phenylethyl)-1,2,3,4-tetrahydro-5H-1,3,4-benzothiadiazepin-5-one (2d). Yield 85%; mp
177-179oC. 1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 1.79 (1H, m, CH2CH2Ph); 2.02 (1H, m, CH2CH2Ph);
2.66 (1H, m, CH2CH2Ph); 2.78 (1H, m, CH2CH2Ph); 4.52 (1H, dd, J = 6.0, J = 5.5, H-2); 5.88 (1H, br. s, NH);
7.22-7.63 (9H, m, Ar); 9.53 (1H, d, J = 4.0, NHCO). Found, %: C 67.63; H 5.74; N 9.77. C16H16N2OS.
Calculated, %: C 67.58; H 5.67; N 9.85.
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