1336
A. Kornicka and M. Gdaniec
Vol 49
42.7 (C4, C5‐imidaz.). Anal. Calcd. for C10H13N5O: C, 54.78; H,
5.98; N, 31.94. Found: C, 54.58; H, 5.61; N, 31.97.
(C2‐imidaz.), 150.7, 133.9, 129.1, 114.1, 111.4, 111.1 (6C), 43.0 (br s
C4, C5‐imidaz.), 29.3 (CH3).
General procedure for the preparation of zwitterionic 2‐
amino‐N′‐(imidazolidin‐2‐ylidene)benzohydrazides (7b–e). The
reaction of 2‐chloro‐4,5‐dihydroimidazole (5) (2.5 g, 24.7 mmol)
in CH2Cl2 (30 mL) with equimolar amount of the appropriate
2‐aminobenzohydrazide 6b–e (24.7 mmol) was carried out
according to the procedure described above for 7a except the
extraction with CH2Cl2. The crude product thus obtained was
purified by crystallization from a suitable solvent. In this
manner, the following compounds were obtained.
General procedure for the preparation of 3‐(imidazolidin‐
2‐ylideneamino)‐2‐thioxo‐2,3‐dihydroquinazolin‐4(1H)‐ones
(8a–e). To a stirred mixture of the appropriate N′‐(imidazolidin‐2‐
ylidene)benzohydrazide 7a–e (8.9 mmol) and Et3N (1.24 mL,
0.9 g, 8.9 mmol) in anhydrous acetone (20 mL) carbon disulfide
(6.23 g, 82.0 mmol) was added dropwise. After stirring for 48–72
h at rt (until H2S had ceased), the solid that precipitated was
filtered off, washed with acetone and dried. Then, the crude
product thus obtained was treated with hot anhydrous methanol
(1:20). The insoluble solid was separated by suction, washed with
hot methanol, and dried to give pure compounds 8a–c, e. The
product 8d was purified by crystallization from DMF/MeOH.
3‐(Imidazolidin‐2‐ylideneamino)‐2‐thioxo‐2,3‐
dihydroquinazolin‐4(1H)‐one (8a). Yield 1.36 g (69.7%). White
solid, mp 284–286°C (dec); IR (KBr): ν 3375, 3220 (NH), 1675
(C═O), 1625 (C═N), 1215 (C═S) cm−1; 1H NMR (500 MHz,
DMSO‐d6): δ 12.59 (s, 1H, HN-C═S), 7.90 (d, J = 7.8 Hz, 1H,
CH‐aromat.), 7.67 (t, 1H, CH‐aromat.), 7.37 (d, J = 8.3 Hz, 1H,
CH‐aromat.), 7.26 (t, 1H, CH‐aromat.), 6.64 (s, 1H, NH), 6.52 (s,
1H, NH), 3.37–3.34 (m, 2H, CH2, imidaz.), 3.29–3.26 (m, 2H,
CH2, imidaz.); 13C NMR (50 MHz, DMSO‐d6) δ 174.6 (CS),
164.4 (CO), 158.1 (C2‐imidaz.), 139.2, 134.4, 127.3, 123.6, 116.8,
115.5 (6C), 42.3 (C4, C5‐imidaz.). Anal. Calcd. for C11H11N5OS:
C, 50.56; H, 4.24; N, 26.80. Found: C, 50.32; H, 4.01; N, 26.53.
7‐Chloro‐3‐(imidazolidin‐2‐ylideneamino)‐2‐thioxo‐2,3‐
dihydroquinazolin‐4(1H)‐one (8b). Yield 2.1 g (79.8%). White
solid, mp 255–257oC (dec); IR (KBr): ν 3385, 3235 (NH), 1665
Zwitterionic 2‐amino‐4‐chloro‐N′‐(imidazolidin‐2‐ylidene)
benzohydrazide (7b). Yield 2.24 g (36.0%). White solid, mp
230–232°C (dec, DMF); IR (KBr): ν 3445, 3390 (NH2), 3330–2850
(max: 3290, 3100, 2970, 2890 NH⊕, CH), 1700 (CN), 1650, 1600,
1
1560 cm–1; H NMR (500 MHz, DMSO‐d6): δ 7.68 (br s, 1H,
CH‐aromat.), 7.02 (br s, 1H, NH), 6.65 (s, 3H, CH‐aromat. and
NH2), 6.48–6.40 (m, 1H, CH‐aromat.), 3.45 (s, 4H, 2× CH2,
imidaz.). Anal. Calcd. for C10H12ClN5O: C, 47.34; H, 4.77; N,
27.61. Found: C, 47.01; H, 4.32; N, 27.55.
Zwitterionic 2‐amino‐5‐chloro‐N′‐(imidazolidin‐2‐ylidene)
benzohydrazide (7c). Yield 1.65 g (26.4%). White solid, mp
208–210oC (dec, DMF/MeOH); IR (KBr): ν 3473, 3330 (NH2),
3250–2830 (max: 3235, 2900, 2830 NH⊕, CH), 1695 (CN), 1604,
1
1565 cm−1; H NMR (500 MHz, DMSO‐d6): δ 7.71 (br s, 1H,
CH‐aromat.), 6.96 (br s, 1H, CH‐aromat.), 6.63 (d, J = 7.3 Hz,
1H, CH‐aromat.), 6.50 (br s, 2H, NH2), 3.64 (br s, 4H, 2× CH2,
imidaz.); 13C NMR (50 MHz, DMSO‐d6): δ 163.9 (NCO), 157.5
(br s, C2‐imidaz.), 147.3, 128.8, 128.6, 120.0, 117.6, 117.1 (6C),
42.8 (C4, C5‐imidaz.). Anal. Calcd. for C10H12ClN5O: C, 47.34;
H, 4.77; N, 27.61. Found: C, 47.42; H, 4.83; N, 27.97.
1
(C═O), 1630 (C═N), 1205 (C═S) cm−1; H NMR (200 MHz,
DMSO‐d6): δ 12.59 (br s, 1H, HN-C═S), 7.89 (d, J = 8.5 Hz,
1H, 5‐H, CH‐aromat.), 7.37 (s, 1H, 8‐H, CH‐aromat.), 7.28
(dd, J6,8 = 1.6 Hz, J6,5 = 8.5 Hz, 1H, 6‐H, CH‐aromat.), 6.68
(br s, 1H, NH), 6.56 (br s, 1H, NH), 3.33–3.16 (m, 4H, 2× CH2,
imidaz.); 13C NMR (50 MHz, DMSO‐d6) δ 174.9 (CS), 164.4
(CO), 157.5 (C2‐imidaz.), 140.2, 138.9, 129.5, 123.7, 115.7, 114.8
(6C), 42.3 (C4, C5‐imidaz.). Anal. Calcd. for C11H10ClN5OS: C,
44.67; H, 3.41; N, 23.68. Found: C, 44.32; H, 3.17; N, 23.39.
6‐Chloro‐3‐(imidazolidin‐2‐ylideneamino)‐2‐thioxo‐2,3‐
dihydroquinazolin‐4(1H)‐one (8c). Yield 1.82 g (69.2%). White
solid, mp 310–312oC (dec); IR (KBr): ν 3395, 3210 (NH), 1670
Zwitterionic 2‐amino‐N′‐(imidazolidin‐2‐ylidene)‐5‐
methylbenzohydrazide (7d). Yield 2.13 g (37.0%). White
solid, mp 226–228oC (dec, acetonitrile); IR (KBr): ν 3475, 3325
(NH2), 3300–2800 (max: 3225, 2900, 2825 NH⊕, CH), 1695 (CN),
1
1620, 1575 cm–1; H NMR (200 MHz, DMSO‐d6): δ 7.40 (s, 1H,
6‐H, CH‐aromat.), 6.84 (d, J = 8.1 Hz, 1H, 3‐H, CH‐aromat.), 6.53
(d, J = 8.1 Hz, 1H, 4‐H, CH‐aromat.), 6.01 (br s, 2H, NH2), 3.40 (s,
4H, 2× CH2, imidaz.), 2.14 (s, 3H, CH3); 13C NMR (50 MHz,
DMSO‐d6): δ 165.0 (NCO), 159.8 (br s, C2‐imidaz.), 146.2, 130.6,
128.8, 122.5, 117.4, 115.8 (6C), 42.4 (C4, C5‐imidaz.), 20.2 (CH3).
Anal. Calcd. for C11H15N5O: C, 56.64; H, 6.48; N, 30.02. Found:
C, 56.31; H, 6.13; N, 29.70.
1
(C═O), 1625 (C═N), 1215 (C═S) cm−1; H NMR (200 MHz,
DMSO‐d6): δ 12.70 (br s, 1H, HN-C═S), 7.82 (d, J5,7 = 2.4 Hz,
1H, 5‐H, CH‐aromat.), 7.72 (dd, J7,5 = 2.4 Hz, J7,8 = 8.8 Hz, 1H,
7‐H, CH‐aromat.), 7.38 (d, J8,7 = 8.8 Hz, 1H, 8‐H, CH‐aromat.),
6.63 (br s, 1H, NH), 6.52 (br s, 1H, NH), 3.30 (br s, 4H, 2× CH2);
13C NMR (50 MHz, DMSO‐d6) δ 174.6 (CS), 163.7 (CO), 157.2
(C2‐imidaz.), 138.1, 134.7, 127.7, 126.2, 118.1, 117.9 (6C), 42.4
(C4, C5‐imidaz.). Anal. Calcd. for C11H10ClN5OS: C, 44.67; H,
3.41; N, 23.68. Found: C, 44.82; H, 3.71; N, 23.94.
Zwitterionic N′‐(imidazolidin‐2‐ylidene)‐2‐(methylamino)
benzohydrazide (7e). Yield 2.36 g (41.0%). White solid, mp
221–223°C (dec, DMF); IR (KBr): ν 3350–2810 (max: 3310,
3210, 3030, 2905, 2815 NH, NH⊕, CH), 1700 (CN), 1605, 1580
cm−1; 1H NMR (500 MHz, DMSO‐d6): δ 7.80 (br s, 1H,
NHCH3), 7.68 (br s, 1H, 6‐H, CH‐aromat.), 7.19–7.09 (m, 1H,
4‐H, CH‐aromat.), 6.52 (d, J = 7.8 Hz, 1H, 3‐H, CH‐aromat.), 6.48 (t,
1H, 5‐H, CH‐aromat.), 3.44 (s, 4H, 2× CH2, imidaz.), 2.77 (d, J = 4.4
Hz, 3H, NHCH3); 13C NMR (125 MHz, DMSO‐d6): δ 165.0 (NCO),
158.9 (br s, C2‐imidaz.), 149.1, 130.2, 128.8, 118.1, 113.6, 109.4
(6C), 42.4 (C4, C5‐imidaz.), 29.5 (CH3). Anal. Calcd. for C11H15N5O:
C, 56.64; H, 6.48; N, 30.02. Found: C, 56.86; H, 6.71; N, 30.10.
NMR analysis of compound 7e/A. 1H NMR (500 MHz,
DMSO‐d6 + TFA): δ 10.55 (br s, 2H, NH⊕2 ), 10.38 (s, 1H,
HN-C═O), 8.84 (br s, 1H, NH⊕), 8.61 (br s, 1H, NH⊕), 7.68
(d, J = 7.3 Hz, 1H, 6‐H, CH‐aromat.), 7.37 (t, 1H, 4‐H, CH‐aromat.),
6.70 (d, J = 7.4 Hz, 1H, 3‐H, CH‐aromat.), 6.60 (t, 1H, 5‐H,
CH‐aromat.), 3.66 (br s, 4H, 2× CH2, imidaz.), 2.80 (s, 3H, NHCH3);
13C NMR (125 MHz, DMSO‐d6 + TFA): δ 169.1 (HN-C═O), 161.4
3‐(Imidazolidin‐2‐ylideneamino)‐6‐methyl‐2‐thioxo‐2,3‐
dihydroquinazolin‐4(1H)‐one (8d). Yield 1.32 g (53.9%). White
solid, mp 298–301oC (dec); IR (KBr): ν 3370, 3205 (NH), 1670
1
(C═ O), 1630 (C═ N), 1215 (C═S) cm−1; H NMR (200 MHz,
DMSO‐d6): δ 12.53 (br s, 1H, HN-C═S), 7.70 (s, 1H, CH‐aromat.),
7.49 (d, J = 7.8 Hz, 1H, CH‐aromat.), 7.27 (d, J = 9.4 Hz, 1H,
CH‐aromat), 6.56 (br s, 1H, NH), 6.50 (br s, 1H, NH), 3.35–3.29
(m, 4H, 2× CH2, imidaz.), 2.35 (s, 3H, CH3); 13C NMR (50 MHz,
DMSO‐d6) δ 174.1 (CS), 164.5 (CO), 158.0 (C2‐imidaz.), 137.2,
135.5, 133.0, 126.6, 116.6, 115.5 (6C), 42.3 (C4, C5‐imidaz.),
20.7 (CH3). Anal. Calcd. for C12H13N5OS: C, 52.35; H, 4.76; N,
25.44. Found: C, 52.01; H, 4.41; N, 25.14.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet