N-(2-aminobenzoyl)-N-methylhydrazones of aldehydes and aldoses and their cyclization to benzo-1,3,4-triazepine derivatives

Article abstract of DOI:10.1007/s10593-011-0697-0

The products of the condensation of aliphatic aldehydes with N-(2-aminobenzoyl)-N-methylhydrazine exist in DMSO-d₆ solution as tautomeric mixtures of linear aldohydrazone and cyclic benzo-1,3,4-triazepine forms. The linear tautomer predominates

Full text of DOI:10.1007/s10593-011-0697-0

Chemistry of Heterocyclic Compounds, Vol. 46, No. 12, March, 2011 (Russian Original Vol. 46, No. 12, December, 2010)
N-(2-AMINOBENZOYL)-N-METHYLHYDRAZONES
OF ALDEHYDES AND ALDOSES AND THEIR
CYCLIZATION TO BENZO-1,3,4-TRIAZEPINE
DERIVATIVES
A. Yu. Ershov1*, B. V. Chernitsa1, V. A. Doroshenko1,
S. I. Yakimovich2, V. V. Alekseyev3, I. V. Lagoda4,
V. V. Pakal'nis2, I. V. Zerova2, and V. V. Shamanin1
The products of the condensation of aliphatic aldehydes with N-(2-aminobenzoyl)-N-methylhydrazine
exist in DMSO-d6 solution as tautomeric mixtures of linear aldohydrazone and cyclic benzo-1,3,4-
triazepine forms. The linear tautomer predominates for 2-aminobenzoyl-N-methylhydrazones of aromatic
aldehydes. A tautomeric equilibrium is observed in DMSO-d6 for the products of the condensation of the
hydrazide of 2-aminobenzoic acid with a series of aldoses. This equilibrium exists between ,-isomeric
pyranose forms and the open aldosohydrazone form. Isomeric conversion to the seven-membered benzo-
1,3,4-triazepine form is observed for the products of the condensation of aldoses with N-(2-
aminobenzoyl)-N-methylhydrazine.
Keywords: 2-aminobenzoylhydrazones, benzo-1,3,4-triazepines, ring-chain tautomerism.
The products of the condensation of carbonyl compounds with N-(2-aminobenzoyl)-N-methylhydrazine
tend to undergo intramolecular cyclization due to nucleophilic addition of the NH2 group to the C=N bond to give
the seven-membered benzo-1,3,4-triazepine ring [1-4]. In some cases, this reaction is reversible, leading to the
existence of the linear N-(2-aminobenzoyl)-N-methylhydrazone and cyclic benzotriazepine forms in solution as
an equilibrium mixture.
_______
* To whom correspondence should be addressed, e-mail: ershov305@mail.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.
3S. M. Kirov Military Medical Academy, Saint-Petersburg 194044, Russia; e-mail: alekseyevv.v@mail.ru.
4Scientific Research Test Center (Medical and Biological Defence), Federal Research Test Institute of Military
Medicine of the Defence Ministry of Russian Federation, Saint-Petersburg 195043, Russia; e-mail:
lagodai@peterstar.ru.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1838-1848, December, 2010.
Original article submitted February 12, 2010.
1486
0009-3122/11/4612-1486©2011 Springer Science+Business Media, Inc.

In the present work, we continued our study of the structure of the products of the condensation of N-(2-
aminobenzoyl)-N-methylhydrazine with a series of aliphatic and aromatic aldehydes as well as aldoses (Table 1)
and their tendency to undergo reversible intramolecular cyclization leading to the seven-membered 1,3,4-
triazepine ring.
R
O
O
O
Me
N
Me
NH
N
H
N
N
RCH=O
NH2
Me
NH2
1a
NH2
N
R
H
A
2a–k
B
2 a R = Me, b R = Et, c R = Pr, d R = Bu, e R = СН2Ph, f R = i-Pr, g R = i-Bu;
hk R = XC6H4, h X = 4-NO2, i X = 3-NO2, j X = H, k X = 4-MeO
The initial compounds studied were the N-(2-aminobenzoyl)-N-methylhydrazones of aliphatic aldehydes
2a-g. These hydrazones were obtained in 50-90% yield after maintaining equimolar amounts of N-(2-amino-
benzoyl)-N-methylhydrazine 1a and the corresponding aliphatic aldehyde in methanol at room temperature (see
Experimental).
TABLE 1. Physicochemical Characteristics of Compounds 2a-k and 4a-h
Found, %
Calculated, %
H
Form in
crystalline
state
——————
Com-
pound
Empirical
formula
mp, оС
Yield, %
С
N
C10H13N3O
C11H15N3O
C12H17N3O
C13H19N3O
C16H17N3O
C12H17N3O
C13H19N3O
C15H14N4O3
C15H14N4O3
C15H15N3O
C16H17N3O2
C12H17N3O5
C12H17N3O5
C13H19N3O6
C13H19N3O6
C13H19N3O5
C13H19N3O5
C14H21N3O6
C14H21N3O6
62.78
62.81
64.30
64.37
65.77
65.73
66.87
66.92
71.95
71.89
65.67
65.73
66.98
66.92
60.34
60.40
60.46
60.40
71.07
71.13
67.75
67.83
57.71
57.67
57.71
57.67
49.80
49.84
49.89
49.84
52.47
52.52
6.91
6.85
7.44
7.37
5.76
5.81
8.26
8.21
6.36
6.41
5.88
5.81
8.17
8.21
4.79
4.73
4.65
4.73
6.04
5.97
5.97
6.05
5.76
5.81
5.76
5.81
6.06
6.11
6.19
6.11
6.39
6.44
22.04
21.97
20.51
20.47
19.09
19.16
17.96
18.01
15.63
15.72
19.07
19.16
18.08
18.01
18.70
18.78
18.84
18.78
16.63
16.59
14.88
14.83
13.39
13.45
13.39
13.45
13.37
13.41
13.47
13.41
14.08
14.13
153-155
55
50
60
50
65
60
60
90
70
60
70
55
50
45
50
45
50
40
45
2а
2b
2c
2d
2e
2f
B
B
B
B
B
B
B
A
A
A
A
A
C
C
C
B
B
B
B
(157-159 [2])
140-142
154-156
142-144
130-132
102-104
132-134
2g
2h
2i
200-202
(204-206 [7])
152-154
127-130
(131-133 [2])
134-136
(134-140 [7])
2j
2k
4а
4b
4c
4d
4e
4f
159-160
189-190
160-164
190-193
112-114
168-171
130-132
116-118
52.59
52.52
51.29
51.37
51.41
51.37
6.50
6.44
6.40
6.47
6.55
6.47
14.06
14.13
12.93
12.84
12.79
12.84
4g
4h
1487

1
The change in the H NMR spectra over time indicates that compounds 2a-g exist in the crystalline state
1
in the cyclic triazepine form B. A single set of signals corresponding to this form is observed in the H NMR
spectrum of 2a-g taken immediately after dissolution in DMSO-d6. This conclusion follows from observation of
the doublet for the NH protons at 5.70-5.90 ppm and signal with the corresponding multiplicity at 4.00-4.50 ppm
for H-2. The signal for the sp3-hybridized carbon atom at 70-75 ppm for C(2) corresponds to triazepine form B in
the 13C NMR spectrum (Tables 2 and 3) [2, 3].
Signals corresponding to the linear 2-aminobenzoylhydrazone form A appear in the 1H NMR spectra 24 h
after dissolution of the compounds in DMSO-d6. A typical diagnostic of this form, whose content for these
compounds does not exceed 12%, is the downfield signal for the azomethine group protons at 7.10-7.40 ppm in
1
the H NMR spectrum and signals for the C=N group carbon at 147 ppm and C=O group carbon at 171 ppm in
13
the C NMR spectrum (Table 2). The spectra of compounds 2a-g do not undergo further change, indicating the
establishment of a ring-chain equilibrium in solution.
The position of the equilibrium depends on the length and branching of the alkyl substituent. The fraction
of linear form A increases in going to compounds 2f,g, which contain bulky isopropyl and isobutyl groups,
respectively. A clear correlation of the position of the tautomeric equilibrium with the steric constants of the alkyl
substituents could not be established due to the low content of form A. Cyclic triazepine form B is markedly
stabilized in going from polar, strongly basic, aprotic solvents such as DMSO-d6 and DMF-d7 to weakly-polar
CDCl3 and is the only species observed in CDCl3 for all the compounds studied, 2a-g.
TABLE 2. 1H NMR Spectra of Compounds 2a-g
Com-
pound
Chemical shifts (DMSO-d6), δ, ppm (J, Hz)
2a
Form А (1%): 1.39 (3H, d, J = 6.0, СН3); 3.25 (3H, s, СН3N);
5.15 (2H, br. s, NH2); 7. 39 (1Н, q, J = 6.0, HC=N)
Form B (99%): 1.24 (3H, d, J = 6.2, СН3); 3.08 (3H, s, СН3N);
4.45 (1Н, dq, J1 = 6.8, J2 = 6.2, H-2); 5.87 (1Н, d, J = 6.8, NН);
6.23 (1Н, br. s, NH); 6.65-7.63 (4Н, m, Ar)
2b
2c
2d
2e
2f
Form А (2%): 0.94 (3H, t, J = 7.4, СН3); 3.27 (3H, s, СН3N);
5.17 (2H, br. s, NH2); 7. 28 (1Н, t, J = 4.8, HC=N)
Form B (98%): 0.98 (3H, t, J = 7.2, СН3); 1.55 (2H, m, СН2); 3.07 (3H, s, СН3N);
4.09 (1Н, dt, J1 = 6.6, J2 = 6.0, H-2); 5.87 (1Н, d, J = 6.6, NН);
6.27 (1Н, br. s, NH); 6.65-7.64 (4Н, m, Ar)
Form А (2%): 0.91 (3H, t, J = 7.0, СН3); 3.23 (3H, s, СН3N);
5.17 (2H, br. s, NH2); 7. 37 (1Н, t, J = 6.2, HC=N)
Form B (98%): 0.93 (3H, t, J = 6.8, СН3); 1.53 (4H, m, 2СН2);
3.06 (3H, s, СН3N); 4.27 (1Н, dt, J1 = 6.6, J2 = 6.0, H-2);
5.87 (1Н, d, J = 6.6, NН); 6.26 (1Н, br. s, NH); 6.67-7.63 (4Н, m, Ar)
Form А (2%): 0.90 (3H, t, J = 7.2, СН3); 3.23 (3H, s, СН3N);
5.19 (2H, br. s, NH2); 7. 36 (1Н, t, J = 6.0, HC=N)
Form B (98%): 0.91 (3H, t, J = 7.2, СН3); 1.34 (2H, m, СН2); 1.48 (4H, m, СН2);
3.06 (3H, s, СН3N); 4.16 (1Н, dt, J1 = 6.6, J2 = 5.5, H-2);
5.87 (1Н, d, J = 6.6, NН); 6.26 (1Н, br. s, NH); 6.65-7.64 (4Н, m, Ar)
Form А (3%): 3.29 (3H, s, СН3N); 3.48 (2Н, d, J = 5.2, СН2);
5.24 (2H, br. s, NH2); 7. 40 (1Н, t, J = 5.2, HC=N)
Form B (97%): 2.79, 2.91 (2Н, ABX system, JАВ = 12.5, CH2);
2.93 (3Н, s, СН3N); 4.46 (1Н, dd, ABX system, JАХ = 6.0, JВХ = 4.5, Н-2);
5.98 (1Н, br. s, NH); 6.31 (1Н, br. s, NH); 6.60-7.65 (9H, m, Ar)
Form А (7%): 0.96 (6H, d, J = 7.0, 2СН3); 2.67 (1H, m, СН); 3.21 (3H, s, СН3N);
5.19 (2H, br. s, NH2); 7.10 (1Н, d, J = 7.6, HC=N)
Form B (93%): 0.93 (3H, d, J = 6.8, СН3); 1.01 (3H, d, J = 6.8, СН3);
1.83 (1H, m, СН); 3.04 (3H, s, СН3N); 3.93 (1Н, dd, J1 = 7.6, J2 = 5.2, H-2);
5.70 (1Н, d, J = 7.6, NН); 6.32 (1Н, br. s, NH); 6.62-7.68 (4Н, m, Ar).
2g
Form А (12%): 0.87 (6H, d, J = 6.6, 2СН3); 2.03 (1Н, m, СН); 3.29 (3H, s, СН3N);
5.18 (1Н, br. s, NH2); 7. 23 (1Н, t, J = 5.6, HC=N)
Form B (88%): 0.93 (6Н, d, J = 6.6, 2СН3); 1.41 (2Н, m, СН2); 1.88 (1Н, m, СН);
3.07 (3H, s, СН3N); 4.24 (1Н, dt, J1 = 6.6, J2 = 6.2, H-2);
5.88 (1Н, d, J = 6.6, NН); 6.20 (1Н, br. s, NH); 6.65-7.65 (4Н, m, Ar)
1488

TABLE 3. 13C NMR Spectra of Compounds 2a-c,e,f,j
Chemical shifts (DMSO-d6), δ, ppm
Com-
pound
Form
C(2)
or С=N
СH3N
С=О
R
38.55
38.51
38.55
38.35
38.34
28.32
38.53
28.63
70.14
75.82
74.09
75.91
78.62
147.00
72.57
147.28
171.74
171.79
171.79
172.01
171.65
170.07
171.70
170.54
21.46 (СН3)
2а
2b
2c
2e
2f
B
B
B
B
B
А
B
A
9.93 (СН3); 27.62 (CH2)
13.97 (СН3); 18.29, 36.81 (2CH2)
40.73 (CH2); 126.23-139.39 (Ar)
16.84, 18.94 (2CH3); 31.80 (CH)
22.25 (2СН3); 26.10 (CH); 41.07 (CH2)
22.14 (CH); 23.20, 23.98 (2CH3); 43.57 (CH2)
128.70-135.08 (Ar)
2g
2j
Thus, the products of the condensation of aliphatic aldehydes with N-(2-aminobenzoyl)-N-methyl-
hydrazine have benzo-1,3,4-triazepine structure in the crystalline state. Partial conversion to the linear form
occurs only in solutions in strongly polar solvents. Thus, the term "N-(2-aminobenzoyl)-N-methylhydrazone"
should be considered as tentative for such compounds.
We should have expected that N-(2-aminobenzoyl)-N-methylhydrazones of aromatic aldehydes would
exist largely in linear form A due to stabilization related to inclusion of the aromatic ring into the -p--conju-
gation system of the acylhydrazone fragment [5-7]. This hypothesis is fully supported by an NMR study of the
structure of compounds 2h-k.
1
The H NMR spectrum of the N-(2-aminobenzoyl)-N-methylhydrazone of benzaldehyde 2j in DMSO-d6
taken both immediately upon preparation and several days after dissolution in a solvent show a single set of
signals corresponding to the linear form A: the signal for the azomethine proton appears at 8.15 ppm, while the
broad singlet of the NH2 group protons appears at 5.35 ppm (Table 4). The existence of linear form A for
compound 2j was also supported by the 13C NMR spectrum (Table 3).
Four structures are possible for the acylhydrazones of carbonyl compounds differing in the arrangement
of the substituents relative to the C=N bond (geometrical (Z,E)-isomerism) and the amide fragment C–N bond
(conformational (Z',E')-isomerism) [5, 6]. The derivatives of aromatic aldehydes exist predominantly or entirely
1
13
in the (E)-configuration relative to the C=N bond. Thus, the signals of linear form A in the H and C NMR
spectra of the N-(2-aminobenzoyl)-N-methylhydrazone of benzaldehyde 2j should be assigned to one of the
(E')- or (Z')-conformers of this structural isomer.
Without going into a detailed discussion of the spectral differences between the (E,E')- and (E,Z')-forms,
we only note the position of the chemical shifts of the C=N and C=O group carbon atoms in the 13C NMR spectra:
the signals of the (E')-isomer of these groups are in the vicinity of 145 and 170 ppm, respectively, while these
signals for the (Z')-isomer lie at 150 and 160 ppm, respectively [8, 9]. Thus, the chemical shifts of the C=N and
C=O group carbon atoms given in Table 3 for form A of compound 2j correspond to (E,E')-structural
arrangement of the N-(2-aminobenzoyl)-N-methylhydrazone fragment in this molecule.
TABLE 4. 1H NMR Spectra of Compounds 2h-k
Chemical shifts (DMSO-d6), δ, ppm.
Compound
СH3N, s, 3H
HC=N, s, 1H
NH2, br. s, 2Н
Ar, m
3.48
3.33
3.36
3.36
8.11
8.14
7.99
7.94
5.35
5.34
5.30
5.28
6.56-8.22 (8H)
2h
2i
6.58-8.36 (8H)
6.57-7.52 (9H)
3.75 (3Н, s, ОСН3);
6.57-7.45 (8H)
2j
2k
1489

Formation of the cyclic 1,3,4-triazepine form B was also not detected for the products of the condensation
of N-(2-aminobenzoyl)-N-methylhydrazine with other aromatic aldehydes 2h-k in DMSO-d6. These compounds
exist in linear form A, represented by a single structural (E,E')-isomer, in the crystalline state and in solution. The
linear structure of compounds 2h-k is in full accord with the results of Neuvonen et al. [7] in a 13C NMR spectral
study of the structure of 2-aminobenzoylhydrazones of aromatic aldehydes.
It would seem that some steric access of the C=N bond for intramolecular nucleophilic attack by the
hydrazone NH2 group is a necessary condition for appearance of the cyclic 1,3,4-triazepine tautomer B for N-(2-
aminobenzoyl)-N-methylhydrazones of carbonyl compounds. Such access may be achieved in the case of the
products of the condensation of N-(2-aminobenzoyl)-N-methylhydrazine with aliphatic aldehydes or aldoses,
which represent a latent form of the aliphatic aldehyde function. A study of the structure of the 2-amino-
benzoylhydrazones and N-(2-aminobenzoyl)-N-methylhydrazones of aldoses fully supports our hypothesis.
2-Aminobenzoylhydrazones and N-(2-aminobenzoyl)-N-methylhydrazones 4a-h are the products of
condensation of aldoses, D-ribose 3a, L-arabinose 3b, D-glucose 3c, and D-mannose 3d with N-(2-amino-
benzoyl)-N-methylhydrazine 1a and 2-aminobenzoylhydrazine 1b are complex tautomeric mixtures capable of
cyclization to give a five-membered form C and six-membered form D as well as a seven-membered 1,3,4-tri-
azepine form B.
O
O
OH
Me
R
O
N
N
R1
OH
NH2
NH
+
1
OH
N
NH2
1a,b
HO
OH
H
2
H2N
3
3a–d
OH
R1
O
HO
4
R = Me
5
HO
R
N
H2N
N
B,B'
O
OH
1
5
R1
2
OH
R
N
4
3
H2N
N
H
OH
HO
O
A
O
1
5
4a–h
R
R1
N
2
OH
4
N
H
R1
3
O
5
OH
-C
HO
1
4
HO
2
3
HO
OH
-D
4a–d R = H, e–h R = Me; 1b R = H; 3a,b R1 = H, a D-riboze, b L-arabinose;
c,d R1 = CH2OH, c D-glucose, d D-mannose, a,b,e,f R1 = H, a,e D-ribose,
b,f L-arabinose; c,d,g,h R1 = СH2OH, c,g D-glucose, d,h D-mannose
We should note that each of these forms is capable of existing as two structural isomers (,-isomers of
forms C and D, (Z',E')-conformers of form A, and 2R- and 2S-stereoisomers of form B). Formation of the cyclic
benzo-1,3,4-triazepine form for 2-aminobenzoylhydrazones 4a-d through attack of the NH2 group at the C=N
bond should be considered unlikely. It is known that no tendency has been found for products of the condensation
of the hydrazide of 2-aminobenzoic acid with aldehydes to undergo such a cyclization [7, 10].
1490

1491

In all the experiments, we recorded the 1H and 13C NMR spectra over time and followed the change in the
NMR spectra of the reaction products from immediately after dissolution until the completion of any chemical
transformation. The 13C NMR spectral data served as the major criterion for identification of specific forms in the
solutions of compounds 4a-h. Thus, we would have expected a signal for anomeric carbon C(1) in the pyranose
form C at 85-90 ppm. The analogous signal for five-membered furanose form D would be found at 95-100 ppm.
In case of seven-membered triazepine form B, the signal for atom C(1) should be found upfield at 70-75 ppm,
which is characteristic for an sp3-hybridized carbon atom of a seven-membered ring attached to two nitrogen atoms
[2, 3, 11]. A downfield 13C NMR signal at 150 ppm related to the C=N bond should be diagnostic for
aldosohydrazone form A.
One set of signals belonging to linear form A is observed in the 13C NMR spectrum of the product of the
condensation of the hydrazide of 2-aminobenzoic acid with D-ribose 4a taken immediately after dissolution. This
finding suggests that compound 4a has the same structure in the crystalline state. After 2 days, sets of signals
arise corresponding to the cyclic pyranose form C and furanose form D in the 13C NMR spectrum of the solution.
The 13C NMR signal for atom C(1) at 88.13 ppm is characteristic for form C. The presence of the five-membered
furanose form D is indicated by the signals for C(4) and C(1) at 83.32 and 95.89 ppm, respectively. The spectrum
of compound 4a stops changing after some time, indicating the establishment of a ring-chain equilibrium, in
which linear form A (60%) exists along with the cyclic pyranose C (25%) and furanose D forms (15%) (Table 5).
A single set of signals corresponding to cyclic pyranose form C is observed for the product of
condensation of the hydrazide of 2-aminobenzoic acid with L-arabinose 4b immediately after dissolution. As in
the case of compound 4a, we may assume that the spectral data reflect the structure of compound 4b in the
crystalline state. Sets of signals corresponding both to the five-membered furanose form D and linear
13
13
aldosohydrazone form A gradually arise in the C NMR spectrum in DMSO-d6. The C NMR signal at 151.35
ppm for the C=N carbon is characteristic for linear form A (Table 5).
Going from ribose derivative 4a and arabinose derivative 4b to products of condensation with hexoses
4c,d is accompanied by disappearance of the cyclic furanose form D and linear aldosohydrazone form A from the
equilibrium. In the crystalline state, compounds 4c,d have pyranose structure C, while the 13C NMR spectra
indicate that these compounds in DMSO-d6 solution are represented by geometric ,-isomers of this form.
Thus, in contrast to the results of a study of El-Barbary et al. [12] on the structure of a series of 3,5-di-
substituted 2-aminobenzoylhydrazones of aldoses, in which the linear aldosohydrazone structure was adopted, we
have shown that, in the case of aldose 2-aminobenzoylhydrazones 4a-d, these compounds may convert to
alternative cyclic pyranose and furanose forms and that both ring-chain and ring-linear-ring tautomeric equilibria
are possible.
Different behavior is found for compounds 4e-h, which are the products of the condensation of aldoses
with N-(2-aminobenzoyl)-N-methylhydrazine. The change in the 13C NMR spectra of all these products indicates
13
that they have the cyclic benzo-1,3,4-triazepine structure B in the crystalline state. The C NMR signal for atom
C(1) at 75-80 ppm characteristic for an sp3-hybridized carbon atom in a seven-membered ring attached to two
nitrogen atoms [2, 3, 11] is diagnostic for benzo-1,3,4-triazepine form B. Signals corresponding to a second
1
configurational isomer of the benzo-1,3,4-triazepine form B' are found in the H and 13C NMR spectra of
compounds 4e-h in DMSO-d6. It was impossible to determine the 2R- or 2S-configuration of these derivatives.
1
The H and 13C NMR spectra of solutions of the products of the condensation of aldoses with N-(2-
aminobenzoyl)-N-methylhydrazine stop changing after 4-7 days, indicating that transition to the possible linear
form A and cyclic pyranose form C does not occur.
A tendency to cyclize with formation of a seven-membered benzo-1,3,4-triazepine ring is a common
feature of compounds 4e-h and the previously studied products of the condensation of aldoses with the hydrazide
of 2-methylbenzoic acid. Intramolecular attack by the sulfur atom at the C=N bond of the hydrazone fragment of
the initially-formed linear form leads to coexistence in solution of an additional seven-membered benzo-1,3,4-tri-
azepine tautomer along with the cyclic pyranose tautomer [11].
1492

EXPERIMENTAL
1
The H and 13C NMR spectra were taken on a Bruker AV-400 spectrometer at 400 MHz and AT-500
spectrometer at 125 MHz, respectively with HMDS as the internal standard. The quantitative composition of the
tautomeric forms was determined by integration of the corresponding signals in the 1H NMR spectra. Monitoring
of the reaction course and purity of the products was carried out by thin-layer chromatography on Silufol UV-254
plates using 4:1 benzene–acetone as the eluent for compounds 2a-k and 12:5:4 ethyl acetate–pyridine–water as
the eluent for compounds 4a-h. Hydrazides 1a,b were obtained according to reported methods [2, 10].
N-(2-Aminobenzoyl)-N-methylhydrazones of Aldehydes 2a-k. A mixture of corresponding aldehyde
(15 mmol) and N-(2-aminobenzoyl)-N-methylhydrazine 1a (1.65 g, 10 mmol) in methanol (50 ml) was
maintained at room temperature for 2 h. The crystalline precipitate was filtered off, washed with ether, dried, and
recrystallized from 1:4 benzene–petroleum ether.
2-Aminobenzoylhydrazones and N-(2-aminobenzoyl)-N-methylhydrazones of Aldoses 4a-h. A
mixture of corresponding monosaccharide 3a-d (10 mmol) and N-(2-aminobenzoyl)-N-methylhydrazine 1a or
2-aminobenzoylhydrazine 1b (10 mmol) in methanol (25 ml) was heated at reflux for 2-6 h. After removal of the
solvent, the crystalline precipitate was filtered off, washed with ether, dried, and recrystallized from 1:8
methanol–acetonitrile.
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