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One-Step Synthesis of 2-Substituted N-Ethoxycarbonyl-1 2-dihydropyridines.

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or anthracene (5 mmoles 15 ml), to which solid potassium
acetate has been added, at 60 "C over a period of 20 min, then
8 8 7 ; of l l ) (96Xfound bygaschromatography)or14 --18%of
triptycene (according t o gas chromatography) may beisolated.
dried with MgS04 and vacuum distilled. UV: A,,
= 2921 A;
IR: 0 = 3000, 1700, 1365, 1300-1275 cm-1: N M R : T = 5.43,
5.70, 4.70, 3.27, (H-2, H-3, H-5, and H-6, respectively),
J 2 , 3 = 6.0, J5.6 = 7.0 Hz, b.p. 110 "CjO.0014 torr, yield 55 %.
Received: April 16, 1970
[Z 209 IE]
German version: Angew. Chem. 82, 547 (1970)
Publication delayed at authors' request
Received: April 7 , 1970
[ Z 207 1El
German version: Angew. Chern. 82, 518 (1970)
[*] Prof. Dr. Ch. Ruchardt and Dip1.-Chem. C. C. Tan
Organisch-chemisches Institut der Universitiit
44 Miinster, Orleans-Ring 23 (Germany)
[ l ] This work was supported by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie.
[2] a) Ch. Riichardt, C. C. Tan, and B. Freudenberg, Tetrahedron Letters 1968, 4019; b) Ch. Riichardt and C. C. Tan,
Chem. Ber. 103, 1774 (1970).
[3] L. Frredmann and F. M . Logullo, J. org. Chemistry 34,
3089 (1969).
[4] H . Herwig, W. Metlesics, and H . Zeiss, J. Amer. chem. SOC.
81, 6203 (1959).
(51 D. L. Brydon, J . I . G. Cadogan, D. M . Smith, and J . B.
Thoinson, Chem. Commun. 1967, 721; see also R. W. Franck
and K . Yanagi, J. Amer. chem. SOC.90, 5814 (1968); J . I . G.
Cadogan, J . Cook, M. J . P. Harger, and J . T . Sharp, Chem.
Commun. 1970, 299.
[6] G. R. Chalfont and M . J . Perkins, J. Amer. chem. SOC.89,
3054 (1967).
One-Step Synthesis of 2-Substituted
N-Ethoxycarbonyl-1,2-dihydropyridinest * *I
By Gideon Fraenkel, J. W. Cooper, and C . M . Fink[*]
Pyridine derivatives react only slowly with Grignard compounds t o give poor product yields [ I ] . The same applies t o
N-acylpyridinium salts 121.
We have now found that pyridine derivatives ( I ) react with
ethyl chloroformate and Grignard compounds to give 2alkyl-1-ethoxycarbonyl-1,Z-dihydropyridines (3), the reaction presumably proceeding via the pyridinium chloride (2).
[*I Prof. Dr.
G . Fraenkel, Dr. J. W. Cooper, and C. M. Fink
Department of Chemistry, The Ohio State University,
140 West 18th Avenue, Columbus, Ohio 43210 (USA)
[ * *] This work was supported by the National Science Foundation.
[I] N . Goetz-Luthy, J. Amer. chem. SOC.71, 2254 (1949); W. v.
E. Doering and P. Z. Pasternack, ibid. 72, 145 (1950); R. A .
Benkeser and D. S. Holton, ibid. 73, 5861 (1951).
[2] A . D. Miller and R. Levine, J. org. Chemistry 22, 168 (1957).
[3] C. Fraenkel and J . W. Cooper, Tetrahedron Letters 1968,
7 825.
A New Synthesis of the Quinazoline System
By Gerhard Simchen, Giinfher Entenmann, and
Rolf Zondler [*I
We recently reported on the synthesis of aza and 1,3-thiaza
heterocyclic compounds by cyclizing acylation of a-cyano
and w-thiocyanato carbonyl halides [I]. We have now found
that 1,3-diaza heterocyclic compounds are also accessible by
this method. Reaction of o-cyanophenyl isocyanates ( I ) ,
Z = 0, and o-cyanophenyl isothiocyanates ( I ) , 2 = S, with
hydrogen halide at room temperature in di-n-butyl ether
initially affords carbamoyl and thiocarbamoyl halides (2),
Z = 0 and Z = S, resp.[21, which cyclize at about 7 0 ° C
in the presence of a n excess of hydrogen halide t o the hitherto
and 4undescribed 4-halogeno-2-quinazolones(3u)-(3c)
halogeno-2-quinazolinethiones(3d), respectively.
(34
(36)
(3c)
(3d
Treatment of (3b) with n-butyllithium in hexane gave a red
solution which was found t o contain 2,4-di-terf-butyl-l,2dihydropyridyl-1-lithium by N M R spectroscopy 131. It is
converted into 2,4-di-tert-butylpyridine when the solution is
heated. The low-temperature N M R spectrum of (36) indicates the presence of two rotational isomers.
I-Ethoxycarbonyl-2,4-di-fert-bufyl-1,2-dil~ydropyridine
(3b):
To a mixture of 4-fert-butylpyridine (1.01 g, 7.5 mmoles) and
20 ml of a 0.75 M solution of rert-butylmagnesium chloride in
tetrahydrofuran (15 mmoles) is added ethyl chloroformate
(0.81 g, 7.5 mmoles) a t 0 ° C over a period of 10 min. The
reaction mixture is hydrolyzed with 1 ml of water at O°C,
filtered, and the white precipitate is washed with tetrahydrofuran. The washings are added t o the filtrate which is then
Angew. Chem. infernat. Edit. J Vol. 9 11970) No. 7
H
c1
H
Br
Br
H
CI
C1
0
0
0
S
21 3
348-350
> 350
295-296
87
78
77
70
Ring closure proceeds by nucleophilic attack of the intermediate nitrile-hydrogen halide adducts o n the carbamoyl or
thiocarbamoyl halide (2). The 4-chloro-2-quinazolines (3a)
t o (3c) can also be synthesized without isolation of intermediates by successive passage of phosgene (ca. 1 h) and
hydrogen chloride (cu. 7 h) through a suspension of 2-cyanoanilinium chloride (4) in di-n-butyl ether a t 120'C and at
80 O C respectively. Nucleophilic substitution of the halogen
atoms attached t o C-4 of (3) proceeds readily.
General procedure:
Compound ( I ) , 2 = 0 or S, (0.01 mole) is suspended in
di-n-butyl ether (50 ml). HCl or HBr is passed into the suspension at 80°C for 7 hours. The resulting precipitate is
523
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step, synthesis, one, ethoxycarbonyl, substituted, dihydropyridine
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