2-[2-(2,3-dihydrobenzimidazolylidene)]- and 2-[2-(2,3-dihydropyrido[2,3-d]-imidazolylidene)]-5,5- dimethyl-1,3-cyclohexanediones

Article abstract of DOI:10.1023/A:1019929622048

The reaction of 2-aminocarbonyl-5,5-dimethyl-1,3-cyclohexanedione with 2,3-diaminopyridine, 1,2-phenylenediamine (and its 4-methyl, 4-nitro, 4-carboxy, and 4-benzoyl derivatives), and 3,3-diaminobenzidine gave the corresponding 2-[2-(2,3-dihydrobenzimidaz

Full text of DOI:10.1023/A:1019929622048

Chemistry of Heterocyclic Compounds, Vol. 38, No. 6, 2002
2-[2-(2,3-DIHYDROBENZIMIDAZOLYLIDENE)]-
d
AND 2-[2-(2,3-DIHYDROPYRIDO[2,3- ]-
IMIDAZOLYLIDENE)]-5,5-DIMETHYL-
1,3-CYCLOHEXANEDIONES
N. Tonkikh1, A. Strakovs1, M. Petrova1, V. V. Chernyshev2, and H. Schenk3
The reaction of 2-aminocarbonyl-5,5-dimethyl-1,3-cyclohexanedione with 2,3-diaminopyridine,
1,2-phenylenediamine (and its 4-methyl, 4-nitro, 4-carboxy, and 4-benzoyl derivatives), and
3,3-diaminobenzidine gave the corresponding 2-[2-(2,3-dihydrobenzimidazolylidene)]- and
2-[2-(2,3-dihydropyrido[2,3-d]imidazolylidene)]-5,5-dimethyl-1,3-cyclohexanediones. Their structure
was confirmed by 1H NMR spectroscopic data and X-ray analysis.
Keywords: 2-aminocarbonyldimedone, aromatic 1,2-diamines, 2-[2-(2,3-dihydrobenzimidazolylidene)]-
5,5-dimethyl-1,3-cylohexanediones.
With the aim of preparing pyrido[3,2-b]benzo[e][1,4]diazepines, and related to the reaction products of
2,3-diaminopyridine with 2-formyldimedone [1], we have carried out the reaction of 2-aminocarbonyl-5,5-
dimethyl-1,3-cyclohexanedione (2) with 1,2-phenylenediamine (1a), its 4-methyl (1b), 4-nitro (1c), 4-carboxy
(1d), and 4-benzoyl (1e) derivatives, and with 3,3'-diaminobenzidine (1f), and 2,3-diaminopyridine (1g).
Melting equimolar amounts of the diamine 1a-g with the amide 2 in the presence of catalytic amounts of
p-toluenesulfonic acid gave the 2-[2-(2,3-dihydrobenzimidazolylidene]- (3a-f) and 2-[2-(2,3-dihydropyrido-
[2,3-d]imidazolylidene]-5,5-dimethyl-1,3-cyclohexanediones respectively.
A reasonable number of 1,3-cyclohexanediones with a directly added heterocyclic substituent group at
position 2 have been recorded in the literature [2-15] but data for 2-benzimidazolyl derivatives is absent.
Previously, 3-(2-benzimidazolyl) derivatives have been obtained only in the 4-hydroxy-2-quinolinone
system [16, 17] by the reaction of the corresponding 2-carbethoxy derivatives with o-phenylenediamine. With
the varied biological activity of benzimidazoles [18] in mind, we have used a series of 4-substituted
1,2-phenylenediamines (1a-f) with 2-aminocarbonyldimedone.
The 1H NMR spectra of all of the benzimidazolylidenedimedones 3a-f show singlet, four-proton signals
for C(4) and C(6) of the methylene groups in the dimedone fragment and two-proton, broad singlets for the NH
protons in the range 11.5-13.5 ppm. Their IR spectra show typical NH stretching vibrations at frequencies of
3250-3200 cm-1.
__________________________________________________________________________________________
1
2
Riga Technical University, Riga LV-1658, Latvia; e-mail: marina@osi.lv. M. V. Lomonosov State
3
University, Moscow 119899, Russia.
Amsterdam, Netherlands; e-mail: hs@cryst.chem.uva.nl. Translated from Khimiya Geterotsiklicheskikh
Soedinenii, No. 6, pp. 822-827, June, 2002. Original article submitted January 11, 2001.
Crystallography Laboratory, Amsterdam University 1018 WV,
724
0009-3122/02/3806-0724$27.00©2002 Plenum Publishing Corporation

H .. O
H..O
NH2
NH2
HN
O
N
+
R
N
H
R
.
.
.
.
O
H
O
1a–f
2
3a–f A
1, 3 a R = H; b R = Me; c R = NO2; d R = COOH; e R = COPh. 1f R= C 6H3(NH2)2(3,4);
H ..O
N
3f R =
N
H . .O
H . .O
N
NH2
NH2
2
+
N
R
N
N
H ..O
1g
3g A
O
H
O
O
H ..O
H
N
.
.
H
N
O
N
N
_
+
N
N
N
R
N
N
H
R
.
H
.
H . . O
O
H
O
3g D
4
3b–f B
3b–f C
2
Θ
deg
Fig. 1. Experimental (1) and difference (2) profiles after refinement of the crystal structure of the
nitrobenzimidazole by the Rietveld method. 3. Calculated position of the diffraction peaks.
725

Fig. 2. Hydrogen bonds in the crystal structure of the nitrobenzimidazole 3c.
The spectroscopic parameters quoted above suggest a preferred symmetric structure 3a-fA and 3gA and
exclude the diazepine structures of type 4 as well as the presence of other products of monocondensation formed
as a result of separation of 1 mol of water in the reaction of the diamines 1 and amide 2.
For the benzimidazolyl derivatives 3b-f, besides the tautomeric form 3A, one should consider the
presence of the forms 3B and 3C and in the case of 3g the betaine form 3D as well. The actual presence of a
betaine form in the solid state for compound 3g would contradict the IR spectroscopic data which shows the
absence of ≡N+–H bond stretching frequencies.
The X-ray investigation, in fact on the nitrobenzimidazole 3c, confirmed the presence of the structure
3cA since each N–H hydrogen atom in the sold state is bound by (found in the field of) two oxygen atoms.
TABLE 1. Crystallographic Data for the Nitrobenzimidazole 3c
Formula
C15H15N3O4
Mr
301.30
P21/n
space group
a, Å
22.185(7)
6.355(2)
11.093(4)
115.81(3)
1407.9(9)
12 (0.010, 270)
4
b, Å
c, Å
β, °
V, Å3
F30
Z
Dx, g/cm3
1.421
726

TABLE 2. Atomic Coordinates in the Crystal Structure of the
Nitrobenzimidazole 3c
Atom
x
y
z
Atom
x
y
z
C1
0.1073(7) -0.299(2)
0.0712(6) -0.010(3)
0.1409(6) -0.280(3)
0.1937(6) -0.529(3)
0.2292(5) -0.582(3)
0.361(1)
0.456(1)
0.601(1)
0.512(1)
0.626(1)
0.275(2)
0.184(2)
-0.055(1)
0.139(2)
0.358(1)
0.029(2)
0.346(1)
0.586(1)
0.490(1)
0.421(1)
0.236(1)
0.411(1)
0.039(1)
0.005(2)
C20
O21
C22
H23
H24
H25
H26
H27
H28
H29
H30
H31
H32
H33
H34
H35
H36
H37
-0.0539(8)
-0.0454(6)
-0.192(1)
0.026(4)
0.106(3)
-0.138(3)
-0.066(3)
-0.220(3)
-0.231(3)
-0.218(3)
0.025(3)
0.107(3)
0.168(3)
-0.075(3)
-0.124(3)
-0.165(3)
-0.226(3)
-0.161(3)
0.527(3)
0.158(2) -0.007(1)
0.764(3) -0.093(2)
0.27(1)
-0.01(1)
0.41(1) -0.136(6)
0.77(1)
0.51(1)
0.38(1) -0.062(6)
0.69(1) -0.189(7)
0.236(1)
C2
C3
N4
O5
C6
C7
C8
0.461(7)
0.657(7)
0.0110(7)
-0.0339(8)
-0.1068(6)
-0.0992(8)
-0.0313(6)
-0.1955(7)
0.182(2)
0.342(3)
0.478(4)
0.691(3)
0.552(2)
0.436(4)
0.111(6)
0.080(6)
C9
O10
C11
C12
C13
C14
O15
N16
N17
C18
C19
-0.02(1)
-0.36(1)
-0.34(1)
0.149(6)
0.280(7)
0.688(6)
0.0737(7) -0.108(3)
0.1084(6) -0.087(3)
0.1447(7) -0.381(3)
0.1976(6) -0.619(4)
0.60(1) -0.053(7)
0.76(1)
0.31(1)
0.83(1)
0.178(7)
0.088(7)
-0.062
0.0358(6)
0.0353(6)
-0.0614(7)
-0.1498(7)
0.009(3)
0.172(2)
0.315(3)
0.594(3)
0.88(1) -0.101(7)
TABLE 3. Hydrogen bonds in the Crystal Structure of the
Nitrobenzimidazole 3c
Bond*
l, Å
Bond*
l, Å
Bond*
l, Å
N16···O21
N16···O21i
N17···O10
N17···O10ii
2.68(2)
2.85(2)
2.76(2)
3.13(2)
H30···O21
H30···O21i
H23···O10
H23···O10ii
2.10(6)
2.01(8)
2.21(6)
2.27(8)
N16–H30···O21
N16–H30···O21i
N17–H23···O10
N17–H23···O10ii
121(5)
152(6)
118(5)
160(6)
_______
* Symmetry notations: (i) -x, -y, -z; (ii) -x, 1-y, 1-z.
EXPERIMENTAL
IR spectra were recorded on a Specord 75-IR instrument for suspensions in vaseline oil and in
hexachlorobutadiene. The 1H NMR spectra were recorded on a Bruker WH-90/DS spectrometer (90 MHz) or on
a Varian-BB Mercury (200 MHz) for solutions in CDCl3 or DMSO-d6 with HMDS internal standard
The diamines used came from the Acros and Maybridge companies.
2-[2-(5H- (3a), 5-Methyl- (3b), 5-Nitro- (3c), 5-Carboxy- (3d), and 5-Benzoyl- (3e)
2,3-Dihydrobenzimidazolylidene)]-5,5-dimethyl-1,3-cyclohexanediones, Bis[2,3-dihydro-2-(5,5-dimethyl-
d
2-[2-(2,3-Dihydropyrido[2,3- ]-
1,3-cyclohexanedion-2-ylidene)-5-benzimidazolyl
(3f),
and
imidazolylidene)]-5,5-dimethyl-1,3-cyclohexanedione (3g). A mixture of 2-aminocarbonyldimedone 2
(4 mmol), the corresponding diamine 1 (4 mmol) (in the case of 1f, 2 mmol), and a catalytic amount of
p-toluenesulfonic acid in a broad test tube was fused in an oil bath (bath temperature 200°C) for 25-35 min. The
initial frothing ended with the formation of an oily melt which rapidly solidified. It was recrystallized twice with
the addition of activated carbon.
727

3a. Yield 48%; mp 249-250°C (ethanol–DMF, 10:1). IR spectrum, ν, cm-1: 1625-1615, 1565, 1550;
1
3200-3180. H NMR spectrum (CDCl3), δ, ppm: 1.1 (6H, s, 2CH3); 2.44 (4H, s, 2CH2); 7.36 (4H, m, C6H4);
11.91 (2H, br. s, 2NH). Found, %: C 70.32; H 6.53; N 10.94. C15H16N2O2. Calculated, %: C 70.32; H 6.71;
N 10.97.
3b. Yield 64%; mp 274-275°C (ethanol–DMF, 10:1). IR spectrum, ν, cm-1: 1624, 1580-1560; 3200.
1H NMR spectrum (CDCl3), δ, ppm: 1.11 (6H, s, 2CH3); 2.44 (7H, s, 2CH2, CH3); 7.22 (3H, m, C6H3); 12.72
(2H, br. s, 2NH). Found, %: C 70.88; H 6.60; N 10.19. C16H18N2O2. Calculated, %: C 71.09; H 6.71; N 10.36.
1
3c. Yield 29%; mp 345-346°C (DMF). IR spectrum, ν, cm-1: 1630, 1612. 1570-1550; 3200. H NMR
spectrum (DMSO-d6), δ, ppm: 1.08 (6H, s, 2CH3); 2.38 (4H, s, 2CH2); 7.88 (1H, d, J = 8 Hz, C6H3); 8.27 (1H,
dd, J = 8 Hz, J = 2 Hz, C6H3); 8.66 (1H, d, J = 2 Hz, C6H3); 11.49 (2H, br. s, 2NH). Found, %: C 59.61; H 5.05;
N 13.86. C15H15N3O4. Calculated, %: C 59.79; H 5.02; N 13.95.
3d. Yield 51%; mp 360-362°C (pyridine–DMF, 10:1). IR spectrum, ν, cm-1: 1625-1615, 1565, 1550,
1
1515; 3200-3180. H NMR spectrum (CDCl3), δ, ppm: 1.02 (6H, s, 2CH3); 2.33 (4H, s, 2CH2); 7.83 (2H, m,
C6H3); 8.34 (1H, s, C6H3); 12.9 (1H, br. s, COOH); 13.21 (2H, br. s, 2NH). Found, %: C 63.75; H 5.25; N 9.19.
C16H16N2O4. Calculated, %: C 63.99; H 5.37; N 9.33.
3e. Yield 63%; mp 290-291°C (pyridine). IR spectrum, ν, cm-1: 1640, 1620, 1590, 1550, 1535; 3220.
1H NMR spectrum (CDCl3), δ, ppm: 1.11 (6H, s, 2CH3); 2.44 (4H, s, 2CH2); 7.28-8.02 (8H, m, C6H5, C6H3);
12.94 (2H, s, 2NH). Found, %: C 73.13; H 5.50; N 7.70. C22H20N2O3. Calculated, %: C 73.32; H 5.59; N 7.77.
1
3f. Yield 35%; mp 376-378°C (acetic acid). IR spectrum, ν, cm-1: 1615, 1570; 3300-3200. H NMR
spectrum (DMSO-d6), δ, ppm: 1.02 (12H, s, 4CH3); 2.41 (8H, s, 4CH2); 7.74 (6H, m, 2C6H3); 13.13 (4H, br. s,
4NH). Found, %: C 70.40; H 5.81; N 10.83. C30H30N4O4. Calculated, %: C 70.57; H 5.92; N 10.97.
1
3g. Yield 51%; mp 300-301°C (pyridine). IR spectrum, ν, cm-1: 1628, 1612, 1556; 3200 cm-1. H NMR
spectrum (CDCl3), δ, ppm: 1.09 (6H, s, 2CH3); 2.44 (4H, s, 2CH2); 7.24 (1H, dd, J = 7.5, J = 4.5 Hz, C5H3N);
7.86 (1H, dd, J = 7.5, J =1.5 Hz, C5H3N); 8.38 (1H, dd, J =4.5 Hz, J = 1.5 Hz, C5H3N); 12.99 (2H, br. s, 2NH).
Found, %: C 65.15; H 5.73; N 16.11. C14H15N3O2. Calculated, %: C 65.36; H 5.88; N 16.33
X-ray Structural Investigation. The nitrobenzimidazole 3c was separated as a yellowish colored
powder. The unit cell parameters (Table 1) were determined using the TREOR90 program [19] for the positions
of 30 peaks with the measurements made in a Guinier chamber in the range 0-50° and using CuKα1 radiation.
The space group P21/n was selected based on conditions of systematic extinction. Collection of diffraction data
for solution and refinement of the structure was carried out on a Philips X'pert laboratory θ-2θ diffractometer
with a PW 3056/00 goniometer using CuKα radiation (Ni filter, 40 kV/mA) with stepwise scanning in the range
6-60° 2θ in 0.02° steps and calculation time 15 s for each step. The structure was solved by a systematic search
method [20] and refined using the Rietveld method with the MRIA program [21] to values of Rp = 6.0%,
R
wp = 8.9%, and Rexp = 3.2% (Fig. 1). The atomic coordinates are given in Table 2. In the refinement process the
boundaries of the available bond lengths were applied. The overall thermal factor Uiso for the non-hydrogen
atoms was refined to 0.093(2) Å. For the hydrogen atoms the value Uiso = 0.05 Å2 was fixed.
The crystal packing of the nitrobenzimidazole molecule is characterized as an infinite linear network
(Fig. 2) forming centrosymmetric hydrogen bonds on both sides of the molecule (Table 3).
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