PREPARATION, 1H AND 13C NMR SPECTRA OF SUBSTITUTED 2-BENZOYLAMINOCARBOXAMIDES

Full text of DOI:10.1135/cccc19950150

150
Sedlak, Halama, Kavalek, Machacek, Sterba:
1
PREPARATION, H AND 13C NMR SPECTRA OF SUBSTITUTED
2-BENZOYLAMINOCARBOXAMIDES
Milos SEDLAK, Ales HALAMA, Jaromir KAVALEK, Vladimir MACHACEK
and Vojeslav STERBA
Department of Organic Chemistry,
University of Pardubice, 532 10 Pardubice, The Czech Republic
Received May 17, 1994
Accepted October 7, 1994
A new type of herbicides based on imidazolinones has been introduced into agriculture
under commercial names of Arsenal, Pursuit, Scepter, Assert etc. by American
Cyanamid Company since 1983 (ref.1). These compounds destroy diocotyledonous
weeds and are almost nontoxic for mammals and fish (LD50 rat – 500 mg/kg, LD50
trout – 300 mg/kg) and nonmutagenic according to the AMES test2.
The aim of the present work is to synthesize substituted 2-benzoylaminocarbox-
amides as starting materials for preparation of imidazolinones and potential biologi-
cally active substances (Formulae I – III).
The nitriles I were prepared by the Strecker synthesis from the respective ketones,
potassium cyanide, and aqueous ammonia or methylamine. In the syntheses of nitriles
Ii and Ij, 4-nitroacetophenone was added to the reaction mixtures in benzene solution,
and the reaction mixture contained a phase transfer catalyst. Even at these conditions,
however, the yields of nitriles Ii and Ij were lower (Table I).
The subsequent hydrolysis of nitriles I to amides II was performed either in 98%
sulfuric acid by heating on a water bath or in alkaline medium of aqueous ammonia by
action of hydrogen peroxide at 40 °C. The conditions of hydrolysis were chosen ac-
cording to the state of nitrile at 40 °C. The liquid nitriles Ia – Ih were hydrolyzed in
alkaline medium, the nitriles Ii and Ij in acidic medium. Nitrile Ib was also hydrolyzed
in sulfuric acid because its hydrolysis yields in ammoniacal peroxide were very low.
The hydrolysis of α-aminonitriles in ammoniacal medium is accompanied by reversible
exchange of amino group with the medium3,4. Therefore, the hydrolysis was carried out
in the solution of the corresponding amine. The acylation of aminoamides II to
benzoylamino derivatives IIIa – IIIz was carried out using the respective substituted
benzoyl chlorides in anhydrous chloroform in the presence of one equivalent of
triethylamine. The reaction has high yields (Table I) and the products can easily be
purified by recrystallization from a mixture of chloroform and acetone or benzene and
methanol.
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Sedlak, Halama, Kavalek, Machacek, Sterba:
TABLE I
Physico-chemical data of compounds I, II and III
Calculated/Found
M.p., °C
Yield, %
Formula
(M.w.)
Compound
% C
% H
% N
Id
70a
56
C6H12N2
(112.2)
–
–
–
Ii
109 – 111
C9H9N3O2
(191.2)
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
28
Ij
186 – 190 (dec.)b C10H11N3O2
31
(205.2)
C4H10N2O
(102.1)
C5H12N2O
(116.2)
C9H11N3O3
IIa
IIb
IIi
101 – 103
15
79 – 81
21
115 – 116
54
(209.2)
IIj
123 – 124
C10H13N3O3
(223.2)
50
IIIa
IIIb
IIIc
IIId
IIIe
IIIf
IIIg
IIIh
IIIi
229 – 232
C11H13N3O4
(251.2)
52.58
53.03
5.22
5.39
16.72
17.00
72
156 – 157
C12H16N2O2
(220.3)
65.43
65.66
7.32
7.46
12.72
12.98
67
208 – 209
C12H15N3O4
(265.3)
54.33
54.57
5.70
5.84
15.84
16.07
67
173 – 176
C12H15N3O4
(265.3)
54.33
54.56
5.70
5.87
15.84
15.59
78
142 – 144
C13H18N2O2
(234.3)
66.64
66.71
7.74
7.85
11.96
11.72
64
125 – 127
C14H20N2O2
(248.3)
67.72
67.66
8.12
8.09
11.28
11.32
75
154 – 155
C14H20N2O2
(248.3)
67.72
68.11
8.12
7.91
11.28
10.93
70
167 – 170
C14H20N2O3
(264.3)
63.62
63.86
7.63
7.80
10.60
10.46
53
110 – 111
C13H17ClN2O2
(268.7)
58.10
58.28
6.38
6.57
10.42
10.50
75
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New Compounds
153
TABLE I
(Continued)
Calculated/Found
C
M.p., °C
Yield, %
Formula
(M.w.)
Compound
%
%
H%
IIIj
151 – 152
81
C13H17ClN2O2
(268.7)
58.10
57.91
6.38
6.59
10.42
10.65
IIIk
IIIl
168 – 169
67
C15H20N2O4
(292.3)
61.63
61.40
6.90
7.17
9.58
10.22
169 – 171
61
C13H16Cl2N2O2
(303.2)
51.50
51.76
5.32
5.15
9.24
9.50
IIIm
IIIn
IIIo
IIIp
IIIq
IIIr
IIIs
IIIt
152 – 154
68
C13H16F2N2O2
(270.3)
57.77
58.00
5.97
6.11
10.36
10.01
168 – 170
98
C13H17N3O4
(279.3)
55.90
55.62
6.13
6.02
15.05
14.78
181 – 183
81
C13H17N3O4
(279.3)
55.90
55.56
6.13
5.96
15.05
14.80
204 – 206
94
C13H16N4O6
(324.3)
48.15
48.40
4.97
5.06
17.28
17.03
171 – 172
65
C14H20N2O2
(248.3)
67.72
68.02
8.12
8.01
11.28
10.96
216 – 218
68
C14H19N3O4
(293.3)
57.33
57.60
6.53
6.64
14.33
14.54
139 – 142
61
C15H22N2O3
(278.3)
64.73
64.50
7.97
8.10
10.06
9.89
180 – 183
71
C15H21N3O4
(307.4)
58.62
58.49
6.89
7.07
13.67
14.01
IIIu
IIIv
IIIw
IIIx
IIIy
IIIz
182 – 184
87
C15H20N2O2
(260.3)
69.20
69.50
7.74
7.48
10.76
11.02
201 – 202
70
C14H17N3O4
(291.3)
57.72
57.49
5.88
5.71
14.42
14.22
125 – 128
79
C16H15N3O4
(313.3)
61.34
61.54
4.83
4.92
13.41
13.14
198 – 201
90
C16H14N4O6
(358.3)
53.63
53.41
3.94
3.70
15.64
15.99
206 – 208
86
C17H16N4O6
(372.3)
54.84
54.50
4.33
4.45
15.05
15.26
80 – 82
57
C15H22N2O2
(262.4)
68.67
68.90
8.45
8.18
10.68
11.00
a
b
B.p. at 1.06 kPa; hydrochloride.
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Sedlak, Halama, Kavalek, Machacek, Sterba:
Due to the presence of an asymmetrical carbon atom, the molecules of compounds
Id, IIId – IIIt, IIIz do not possess a plane of symmetry which would halve the angle
between the paired groups (CH(CH3)2, CH2CH3). Hence these groups are aniso-
chronous in 1H and, as the case may be, also 13C NMR spectra. The coupling constants
3J(CH−CH3) are the same, within the experimental error, for both anisochronous methyl
groups. The paired groups in the molecules IIId, IIIe, IIIg, IIIh, IIIj, IIIo, IIIq – IIIt,
IIIw, IIIz are also represented by pairs of protons and carbons in the benzene nuclei.
1
However, no anisochronism of these groups was observed in the H and 13C NMR
spectra.
EXPERIMENTAL
The 1H and 13C NMR spectra (δ, ppm; J, Hz) were measured at 400.13 and 100.62 MHz, respec-
tively, using a Bruker AM 400 spectrometer, or at 360.14 and 90.57 MHz, respectively, using a
Bruker AMX apparatus at 25 °C. For the measurements, the compounds III were dissolved in
hexadeuteriodimethyl sulfoxide (ca 5% solutions). The chemical shifts refer to the middle signal
of the solvent multiplet (δ(1H) 2.55 and δ(13C) 39.6). If not otherwise stated, the NMR spec-
tra of compounds I and II were measured in CDCl3, and the chemical shifts refer to hexamethyl-
disiloxane (δ(1H) 0.05) and the solvent signal (δ(13C) 77.0). The groups CH, CH3 and Cq, CH2 were
resolved by the APT pulse sequence. For compound IIIc, the assignment of chemical shifts of the
carbonyl groups was confirmed by the 13C selective INEPT method. The TLC analyses were carried
out on Silufol (Kavalier, The Czech Republic).
Preparation of Aminonitriles Ia – Ih
2-Amino-2-methylpropanenitrile (Ia), 2-methylamino-2-methylpropanenitrile (Ib), 2-amino-2-methyl-
butanenitrile (Ic), 2-methylamino-2,3-dimethylbutanenitrile (Ie), 2-methylamino-2,4-dimethylpentane-
nitrile (If), 1-aminocyclohexanecarbonitrile (Ig), and 2-amino-2-phenylpropanenitrile (Ih) were
prepared according to ref.5. 2-Amino-2,3-dimethylbutanenitrile (Id) was prepared by an analogous
1
Strecker synthesis from the corresponding ketone. H NMR spectrum: 1.81 br, 2 H (NH2); 1.77 m, 1 H
(CH); 1.41 s, 3 H (CCH3); 1.06 d, 3 H, J = 6.79 (CHCH3); 1.05 d, 3 H, J = 6.87 (CHCH3).
13C NMR spectrum: 123.62 (CN), 53.71 (Cq), 36.96 (CH), 24.63 (CCH3), 17.07 and 16.73
(CH(CH3)2).
2-Amino- and 2-Methylamino-2-(4-nitrophenyl)propanenitriles (Ii and Ij)
A 250 ml flask equipped with a high-speed mixer was charged with benzene (50 ml) and 4-nitro-
acetophenone (10 g, 61 mmol). The solution formed was treated with a solution prepared from potas-
sium cyanide (8 g, 123 mmol), ammonia (40 ml), glacial acetic acid (40 ml), and
benzyltriethylammonium chloride (0.1 g). The mixture was vigorously stirred at 40 °C 24 h. The
upper benzene layer was separated and dried with sodium sulfate. The first portion of product (2.5 g
in the form of hydrochloride) was isolated by introducing gaseous hydrogen chloride. The aqueous
phase was cooled to 5 °C, the separated crystals were collected by suction (2 g) and recrystallized
from a cyclohexane–chloroform mixture. TLC: RF(chloroform) = 0.07, RF(chloroform–methanol
1
3 : 1) = 0.68. H NMR spectrum: 8.31 and 7.93, 4 H (C6H4); 3.31 br, 2 H (NH); 1.73 s, 3 H (CH3).
13C NMR spectrum: 149.96 (C-1), 147.29 (C-4), 126.71 (C-2), 123.97 (CN), 123.81 (C-3), 53.18
(Cq), 30.89 (CH3).
Collect. Czech. Chem. Commun. (Vol. 60) (1995)

New Compounds
155
TABLE II
1H NMR spectra of substituted 2-benzoylaminocarboxamides III
NH2
(2 × brs) (brs)
R1 = H R1 = CH3 C−CH3 CH CH(CH3)
Compound
Ara
Others
(s)
(s)
(m)
(2 × d)
IIIa
IIIb
IIIc
IIId
6.92
7.30
8.59
–
–
1.50
1.43
1.45
1.53
–
–
–
–
–
–
–
–
8.35, 2 H;
8.14, 2 H
6.69
7.15
2.90
2.88
–
7.56 m, 5 H
6.76
7.31
–
8.34, 2 H;
7.82, 2 H
7.08
7.39
8.31
8.34, 2 H; 2.05 m (CH2);
8.10, 2 H
0.82 t, J = 7.4
(CH2CH3)
IIIe
IIIf
7.22
6.99
7.83
7.78
–
–
1.45
1.49
2.29 0.98, 0.92 7.82 d, 2 H;
–
J = 6.7
7.56 t, 1 H;
7.49 t, 2 H
7.15
7.08
2.27 0.98, 0.94 7.42 d, 2 H;
2.38 s (ArCH3)
2.39 s (ArCH3)
J = 6.8
7.36 t, 1 H;
7.27 t, 2 H
IIIg
IIIh
IIIi
7.20
7.05
7.76
7.67
8.08
–
–
–
1.47
1.47
1.50
2.33 0.98, 0.92 7.75, 2 H;
J = 6.7 7.30, 2 H
2.33 0.98, 0.93 7.82, 2 H
J = 6.8 7.03, 2 H
2.24 0.99, 0.93 7.57 d, 1 H;
7.18
6.98
3.84 s
(ArOCH3)
7.16
7.09
–
–
J = 6.7
7.53 d, 1 H;
7.48 t, 1 H;
7.44 t, 1 H
IIIj
7.19
7.00
7.92
8.09
–
–
1.45
1.46
2.28 0.98, 0.93 7.87, 2 H;
J = 6.8 7.56, 2 H
2.15 0.96, 0.94 7.83 d, 1 H; 3.82 s
IIIk
7.13
7.11
J = 6.9
7.67 t, 1 H; (COOCH3)
7.59 t, 1 H;
7.57 d, 1 H
IIIl
7.26
6.72
8.37
–
1.51
2.20 0.98, 0.95 7.53, 2 H;
–
J = 6.8
7.47, 1 H
(AB2)
IIIm
IIIn
7.18
6.93
8.39
8.34
–
–
1.45
1.46
2.24 0.96, 0.91 7.54 m, 1 H
J = 6.8 7.18 t, 2 H
2.13 0.96, 0.93 8.09 d, 1 H;
–
–
7.12
7.04
J = 6.8
7.84 t, 1 H;
7.75 m, 2 H
IIIo
7.22
7.05
8.18
–
1.48
2.28 1.00, 0.95 8.35, 2 H;
J = 6.8 8.09, 2 H
–
Collect. Czech. Chem. Commun. (Vol. 60) (1995)

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Sedlak, Halama, Kavalek, Machacek, Sterba:
TABLE II
(Continued)
NH2
(2 × brs) (brs)
R1 = H R1 = CH3 C−CH3 CH CH(CH3)
Compound
Ara
Others
(s)
(s)
(m)
(2 × d)
IIIp
7.31
6.98
8.59
–
1.47
2.27 1.02, 1.00 9.05 d, 2 H;
–
J = 6.9
8.99 t, 1 H
(A2X)
IIIq
IIIr
IIIs
IIIt
7.13
6.74
–
–
2.90
2.88
2.93
2.91
–
1.39
1.41
1.38
1.48
–
2.89 1.07, 0.89 7.52 m, 2 H;
J = 7.0 7.47 m, 3 H
–
–
7.23
6.76
2.86 1.08, 0.91 8.34, 2 H;
J = 7.0 7.79, 2 H
7.08
6.73
–
2.85 1.06, 0.87 7.52, 2 H;
J = 6.9 7.01, 2 H
3.83 s
(ArOCH3)
7.25
6.73
–
2.09 0.99, 0.95 8.34, 2 H;
1.78 m (CH2)
J = 6.5
7.76, 2 H
b
c
IIIu
IIIv
IIIw
7.01
6.83
7.82
8.25
8.68
–
–
–
–
7.80, 2 H;
7.31, 2 H
7.12
6.78
–
–
–
–
8.35, 2 H;
8.13, 2 H
7.43
7.30
–
1.98
8.32, 2 H;
8.07, 2 H
7.54 d, 2 H;
7.39 t, 2 H;
7.31 t, 1 H
IIIx
IIIy
IIIz
7.60
7.52
9.09
–
–
2.06
1.94
1.47
–
–
–
–
8.25, 2 H;
7.85, 2 H
8.36, 2 H;
8.15, 2 Ha
7.58
7.20
2.88
2.94
8.25, 2 H;
7.84, 2 H
8.39, 2 H;
7.99, 2 Ha
7.12
6.68
–
2.10 0.99, 0.95 7.51 – 7.46 1.77 m (CH2)
J = 6.5
m, 5 H
a
b
If no multiplicity is given, the signal is the AA′XX′ system; 2.40 s (ArCH3), 2.23 brd (H-2); 1.73
c
dt (H-2′); 1.51 m (H-3, H-3′, H-4); 1.28 m (H-4′); 2.23 brd (H-2); 1.78 dt (H-2′); 1.55 m (H-3,
H-3′, H-4); 1.28 m (H-4′).
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Sedlak, halama, Kavalek, Machacek, Sterba:
Collect. Czech. Chem. Commun. (Vol. 60) (1995)

New Compounds
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2-Methylamino-2-(4-nitrophenyl)propanenitrile (Ij) was prepared in the same way. The physical
characteristics are given in Table I.
Preparation of Aminoamides IIa, IIc – IIh
The aminoamides IIa, IIc, IId, IIg, IIh were prepared by hydrolyses of the aminonitriles Ia, Ic, Id, Ig,
Ih using hydrogen peroxide in aqueous ammonia5. The hydrolyses of N-methylaminonitriles Ie, If
1
were carried out similarly in aqueous methylamine. H NMR spectrum of IIa: 7.34 and 6.21 2 bs, 2 H
(NH2CO); 1.7 bs, 2 H (NH2); 136, 6 H (CH3). 13C NMR spectrum of IIa: 181.07 (CO), 54.70 (Cq),
29.05 (CH3).
2-Amino- and 2-Methylamino-2-(4-nitrophenyl)propanamides (IIi and IIj)
and 2-Methylamino-2-methylpropanamide (IIb)
1-Cyano-1-(4-nitrophenyl)ethylammonium chloride (Ii . HCl; 10 g, 44 mmol) was heated on a boiling
water bath with 98% sulfuric acid (35 ml) 80 min. The solution was cooled and poured onto 250 g
crushed ice and neutralized with 40% sodium hydroxide solution to ca pH 9. The separated tarry
portions were filtered off with charcoal, and the raw product IIi, precipitated on cooling, was recry-
stallized from a chloroform–benzene mixture (Table I). TLC: RF(chloroform–methanol 3 : 1) = 0.35.
1H NMR spectrum ((CD3)2SO): 8.23 and 7.82, 4 H (C6H4); 7.47 and 7.23, 2 × bs, 2 H (CONH2);
2.56 bs, 2 H (NH2); 1.60 s, 3 H (CH3). 13C NMR spectrum ((CD3)2SO): 177.11 (CO), 154.34 (C-1),
146.25 (C-4), 127.08 (C-2), 123.04 (C-3), 60.55 (Cq), 27.99 (CH3).
Similar procedure was used to prepare 2-methylamino-2-(4-nitrophenyl)propanamide (IIj) and
2-methylamino-2-methylpropanamide (IIb). IIj: 1H NMR spectrum ((CD3)2SO): 8.24 and 7.77, 4 H
(C6H4); 7.42 and 7.29, 2 × br, 2 H (CONH2); 2.82 bs, 1 H (NH); 2.19 s, 3 H (NCH3); 1.55 s, 3 H
(CCH3). 13C NMR spectrum ((CD3)2SO): 175.68 (CO), 152.42 (C-1), 146.34 (C-4), 127.75 (C-2),
1
123.13 (C-3), 65.27 (Cq), 29.87 (NCH3), 22.91 (CCH3). IIb: H NMR spectrum: 7.09 and 6.39, 2 br,
2 H (NH2); 2.24 s, 3 H (CH3N); 1.23 s, 6 H (C(CH3)2). 13C NMR spectrum: 180.22 (CO), 58.82
(Cq), 30.02 (CH3N), 24.90 (CCH3).
Preparation of Substituted 2-Benzoylaminocarboxamides III. A General Procedure
A solution of respective benzoyl chloride (20 mmol) in chloroform (10 ml) was treated with a
solution of corresponding derivative II (20 mmol) and triethylamine (20 mmol) in chloroform
(35 ml). After 1 h standing, the mixture was heated to boiling 30 min, cooled, extracted with 3 × 30 ml
water, and dried with sodium sulfate. The solvent was distilled off, and the residue was recrystallized
from benzene. The yields, melting points, and elemental analyses of the compounds III prepared
are given in Table I. The substances were identified by means of 1H and 13C NMR spectra (Tables
II and III).
This work was supported by the research grant No. 203/94/0123 of the Grant Agency of the Czech
Republic.
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Sedlak, Halama, Kavalek, Machacek, Sterba:
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4. Pascal R., Taillades J., Commeyras A.: Tetrahedron 34, 2275 (1978).
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Collect. Czech. Chem. Commun. (Vol. 60) (1995)