Novel synthesis of heterocyclic ketene N,N-, N,O-, and N,S-acetals using cyanoketene dithioacetals

Article abstract of DOI:10.1081/SCC-120018927

A novel synthesis of (2,3-dihydrobenzoimidazole-2-ylidenyl)cyanoacetanilide, (2,3-dihydrobenzoxazole-2-ylidenyl)cyanoacetanilide and (2,3-dihydro-benzothiazole-2-ylidenyl)cyanoacetanilide derivatives 5a-l via reaction of ketene dithioacetals 2a-d with o-phenylenediamine, o-aminophenol, and o-aminothiophenol 3a-c is reported and the synthetic potential of the method is demonstrated.

Full text of DOI:10.1081/SCC-120018927

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Novel Synthesis of Heterocyclic Ketene N,N-, N,O-,
and N,S-Acetals Using Cyanoketene Dithioacetals
Galal H. Elgemeie , Ahmed H. Elghandour & Ghada W. Abd Elaziz
To cite this article: Galal H. Elgemeie , Ahmed H. Elghandour & Ghada W. Abd Elaziz (2003)
Novel Synthesis of Heterocyclic Ketene N,N-, N,O-, and N,S-Acetals Using Cyanoketene
Dithioacetals, Synthetic Communications, 33:10, 1659-1664, DOI: 10.1081/SCC-120018927
To link to this article: http://dx.doi.org/10.1081/SCC-120018927
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 10, pp. 1659–1664, 2003
Novel Synthesis of Heterocyclic Ketene
N,N-, N,O-, and N,S-Acetals Using
Cyanoketene Dithioacetals
2
Galal H. Elgemeie,1, Ahmed H. Elghandour,
*
and Ghada W. Abd Elaziz2
1Chemistry Department, Faculty of Science,
Helwan University, Helwan, Cairo, Egypt
2Chemistry Department, Faculty of Science, Cairo
University, Beni-Suef Branch, Beni-Suef, Egypt
ABSTRACT
A novel synthesis of (2,3-dihydrobenzoimidazole-2-ylidenyl)cyano-
acetanilide, (2,3-dihydrobenzoxazole-2-ylidenyl)cyanoacetanilide and
(2,3-dihydro-benzothiazole-2-ylidenyl)cyanoacetanilide derivatives 5a–l
via reaction of ketene dithioacetals 2a–d with o-phenylenediamine, o-
aminophenol, and o-aminothiophenol 3a–c is reported and the synthetic
potential of the method is demonstrated.
*Correspondence: Galal H. Elgemeie, Chemistry Department, Faculty of Science,
Helwan University, Helwan, Cairo, Egypt; E-mail: elgemeie@hotmail.com.
1659
DOI: 10.1081/SCC-120018927
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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1660
Elgemeie, Elghandour, and Abd Elaziz
Key Words: Ketene dithioacetals; O-phenylenediamine; O-ami-
Cyanoketene
nothiophenol; O-aminophenol;
Unsaturated nitriles.
dithioacetals;
Heterocyclic ketene aminals are versatile starting materials for the
synthesis of a wide variety of fused heterocycles. Although their synthesis
and reactions have received much attention,[1] the synthesis and reactions
of their corresponding sulfur and oxygen analogues-heterocyclic ketene
N,S- and N,O-acetals have only been studied in a few cases.[2] Recently,
the synthesis and some reactions of heterocyclic ketene N,S-acetals have
been reported by us.[3,4] Here, we describe the synthesis of some new
heterocyclic ketene N,N-, N,O- and N,S-acetals starting with ketene
dithioacetals 2.[5] Compounds 2 are prepared by the reaction of substi-
tuted acetanilide derivatives 1 with carbon disulfide in the presence of
sodium ethoxide followed by the alkylation with methyl iodide.
Compounds 2 reacted with o-phenylenediamine, o-aminophenol and
o-aminothiophenol 3a–c in refluxing absolute ethanol to afford the
corresponding (benzoimidazol-2-ylidene-, benzoxazole-2-ylidene-, and
benzothiazole-2-ylidene)cyanoacetanilides 5 in good yields (Chart 1).
The structures of compounds 5 were established and confirmed by their
elemental analysis and spectral data (MS, IR, 1H NMR). Thus, structure
of 5a is supported by its mass spectrum which showed a molecular ion
corresponding to the formula C16H12N4O (m/z 276). The 1H NMR
spectrum contained a multiplet at ꢀ ¼ 7.04ꢀ7.67 ppm assigned to the
aromatic protons and three broad singlets at ꢀ ¼ 9.25, 10.42, and
12.23 ppm assigned to three NH groups. The formation of 5 from the
reaction of 2 with 3 is assumed to proceed through nucleophilic attack of
the –NH2, –OH, and –SH groups to the ethylenic double bond followed
by elimination of two moles of methyl mercaptan.
This result indicates that the reaction of N-substituted bis(methyl-
thiomethylene)-cyanoacetamides with o-phenylenediamine, o-aminophe-
nol, and o-aminothiophenol can be utilized as an excellent route for the
synthesis of interesting heterocyclic ketene N,N-, N,O- and N,S-acetal
derivatives, which are otherwise accessible only with difficulty. The
obtained compounds are now under biological evaluation studies.
EXPERIMENTAL
All melting points are uncorrected on a Gallenkamp melting point
1
apparatus. The H NMR spectra were measured on a Varian 400 MHz

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Heterocyclic Ketene N,N-, N,O-, and N,S-Acetals
1661
Chart 1.

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1662
Elgemeie, Elghandour, and Abd Elaziz
spectrometer for solution (CD3)2SO using Si(CH3)4 as an internal
standard. Mass spectra were recorded on a Varian MAT 112 spectro-
meter. Analytical data were obtained from The Microanalytical Data
Center at Cairo University.
(2,3-Dihydrobenzoimidazole-2-ylidenyl)cyanoacetanilides (5a–d), (2,3-
dihydrobenzoxazole-2-ylidenyl)cyanoacetanilides (5e–h), and (2,3-dihydro-
benzothiazole-2-ylidenyl)cyanoacetanilides (5i–l). General procedure: A
mixture of bis(methylthiomethylene)-N-substituted cyanoacetamides
2a–d (0.01 mol) and o-phenylene diamine, o-aminophenol or o-ami-
nothiophenol 3a–c (0.01 mol) was refluxed in ethanol (30 mL) for 4 h.
The resulting precipitated solid product was filtered off and recrystallized
from the appropriate solvent.
5a: White; m.p., 265–267ꢁC; from ethanol; yield, 80%; ꢁmax/cmꢀ1
(KBr) 3425, 3321 (NH); 2191 (CN); 1649 (CO); ꢀH[(CD3)2SO]:
7.04–7.67 (m, 9H, C6H5 and C6H4); 9.25 (s, 1H, NH); 10.42 (s, 1H,
NH); 12.23 (s, 1H, NH); (m/z 276); Found: C, 69.35; H, 4.53; N,
20.39%; Calcd. for C16H12N4O: C, 69.57; H, 4.35; N, 20.29%.
5b: White; m.p., 250–251ꢁC; from methanol; yield, 82%; ꢁmax/cmꢀ1
(KBr) 3445, 3310 (NH); 2199 (CN); 1656 (CO); ꢀH[(CD3)2SO]: 6.87–7.63
(m, 8H, 2C6H4); 9.15 (s, 1H, NH); 10.43 (s, 1H, NH); 12.35 (s, 1H, NH);
(m/z 310); Found: C, 61.66; H, 3.63; N, 18.22%; Calcd. for
C16H11ClN4O: C, 61.84; H, 3.54; N, 18.04%.
5c: White; m.p., 244–245ꢁC; from ethanol; yield, 78%; ꢁmax/cmꢀ1
(KBr) 3415, 3302 (NH); 2178 (CN); 1644 (CO); ꢀH[(CD3)2SO]: 2.26
(s, 3H, CH3); 7.06–7.56 (m, 8H, 2C6H4); 8.71 (s, 1H, NH); 9.00 (s, 1H,
NH); 12.39 (s, 1H, NH); (m/z 290); Found: C, 70.47; H, 4.81; N, 19.49%;
Calcd. for C17H14N4O: C, 70.35; H, 4.83; N, 19.31%.
5d: White; m.p., 254–256ꢁC; from ethanol; yield, 72%; ꢁmax/cmꢀ1
(KBr) 3400, 3250 (NH); 2190 (CN); 1654 (CO); ꢀH[(CD3)2SO]: 3.95
(s, 3H, OCH3), 7.00–7.54 (m, 8H, 2C6H4); 9.00 (s, 1H, NH); 10.12 (s,
1H, NH); 12.09 (s, 1H, NH); (m/z 306); Found: C, 66.81; H, 4.51;
N, 18.20%; Calcd. for C17H14N4O2: C, 66.67; H, 4.58; N, 18.30%.
5e: White; m.p., 256–258ꢁC; from ethanol; yield, 74%; ꢁmax/cmꢀ1
(KBr) 3427, 3318 (NH); 2193 (CN); 1644 (CO); ꢀH[(CD3)2SO]:
7.00–7.80 (m, 9H, C6H5 and C6H4); 9.20 (s, 1H, NH); 10.30 (s, 1H,
NH); (m/z 277); Found: C, 69.54; H, 3.88; N, 15.31%; Calcd. for
C16H11N3O2: C, 69.31; H, 4.00; N, 15.16%.
5f: White; m.p., 245–247ꢁC; from isopropanol; yield, 76%; ꢁmax/cmꢀ1
(KBr) 3440, 3316 (NH); 2198 (CN); 1652 (CO); ꢀH[(CD3)2SO]: 7.38–7.63
(m, 8H, 2C6H4); 8.86 (s, 1H, NH); 10.42 (s, 1H, NH); (m/z 311); Found:
C, 61.84; H, 3.32; N, 13.60%; Calcd. for C16H10ClN3O2: C, 61.64;
H, 3.21; N, 13.48%.

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Heterocyclic Ketene N,N-, N,O-, and N,S-Acetals
1663
5g: White; m.p., 235–236ꢁC; from ethanol; yield, 70%; ꢁmax/cmꢀ1
(KBr) 3414, 3309 (NH); 2182 (CN); 1648 (CO); ꢀH[(CD3)2SO]: 2.23
(s, 3H, CH3); 7.09–7.44 (m, 8H, 2C6H4); 8.79 (s, 1H, NH); 10.11 (s, 1H,
NH); (m/z 288); Found: C, 70.23; H, 4.61; N, 14.34%; Calcd. for
C17H13N3O2: C, 70.10; H, 4.47; N, 14.43%.
5h: White; m.p., 240–242ꢁC; from ethanol; yield, 72%; ꢁmax/cmꢀ1
(KBr) 3412, 3256 (NH); 2192 (CN); 1656 (CO); ꢀH[(CD3)2SO]: 4.09
(s, 3H, OCH3), 7.15–7.88 (m, 8H, 2C6H4); 9.56 (s, 1H, NH); 11.50 (s,
1H, NH); (m/z 307); Found: C, 66.24; H, 4.38; N, 13.86%; Calcd. for
C17H13N3O3 (307): C, 66.45; H, 4.24; N, 13.68%.
5i: Yellow; m.p., 226–227ꢁC; from ethanol; yield, 73%; ꢁmax/cmꢀ1
(KBr) 3416, 3166 (NH); 2198 (CN); 1678 (CO); ꢀH[(CD3)2SO]: 7.22–7.89
(m, 9H, C6H5 and C6H4); 9.45 (s, 1H, NH); 10.56 (s, 1H, NH); (m/z 293);
Found: C, 65.34; H, 3.83; N, 14.45%; Calcd. for C16H11N3OS: C, 65.53;
H, 3.75; N, 14.34%.
5j: Yellow; m.p., 236–238ꢁC; from ethanol; yield, 76%; ꢁmax/cmꢀ1
(KBr) 3420, 3160 (NH); 2195 (CN); 1670 (CO); ꢀH[(CD3)2SO]: 7.07–8.01
(m, 8H, 2C6H4); 9.38 (s, 1H, NH); 12.91 (s, 1H, NH); (m/z 327); Found:
C, 58.41; H, 3.02; N, 13.00%; Calcd. for C16H10ClN3OS: C, 58.63;
H, 3.05; N, 12.82%.
5k: Yellow; m.p., 224–226ꢁC; from ethanol; yield, 77%; ꢁmax/cmꢀ1
(KBr) 3414, 3159 (NH); 2189 (CN); 1648 (CO); ꢀH[(CD3)2SO]: 2.28 (s, 3H,
CH3); 7.09–7.95 (m, 8H, 2C6H4); 9.20 (s, 1H, NH); 12.90 (s, 1H, NH);
(m/z 307); Found: C, 66.57; H, 4.30; N, 13.89%; Calcd. for C17H13N3OS:
C, 66.45; H, 4.24; N, 13.68%.
5l: Yellow; m.p., 220–222ꢁC; from ethanol; yield, 70%; ꢁmax/cmꢀ1
(KBr) 3434, 3163 (NH); 2190 (CN); 1665 (CO); ꢀH[(CD3)2SO]: 4.12 (s, 3H,
OCH3), 6.88–7.70 (m, 8H, 2C6H4); 9.67 (s, 1H, NH); 10.90 (s, 1H, NH);
(m/z 323); Found: C, 63.02; H, 4.01; N, 13.08%; Calcd. for
C17H13N3O2S: C, 63.16; H, 4.03; N, 13.00%.
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3. Elgemeie,G.H.;Elghandour,A.H.;Elzanate,A.M.;Ahmed,S.A.Novel
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1664
Elgemeie, Elghandour, and Abd Elaziz
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Received in the UK January 25, 2001