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The Reaction of O-Ethyl Succinimide with Primary and Secondary Amines. A Simple Synthesis of Some 4(3H)-Quinazolones and Quinazolones Having Propionic Acid at 2-Position

1978; Elsevier BV; Volume: 9; Issue: 10 Linguagem: Inglês

10.3987/r-1978-10-1375

1881-0942

Tatsuo Nagasaka, Fumiko Hamaguchi, N. OZAWA, S. OHKI,

Advanced Synthetic Organic Chemistry

The reaction of 0-ethyl succinimide (I) with various primary and secondary amines ( 11) afforded keto-amidines (I I I) in satisfactory yields.The treatment of keto-amidines (1111, IIIj, and IIIk) prepared from anthranilate and o-acylanil ines with sodium in alcohol afforded quantitatively quinazolones (VIa and VIb) and quinazolines (VId and VIe) having propionic acid ester at 2-position.The sequence of these reactions for quinazolones and quinazolines can be carried out in the same reaction-vessel by successive addition of the reagents.0-Ethyl succinimide (I) was first prepared by Comstock and wheeler1) in 1891.After long silence, some interesting behaviors of this compound (I) were reported by two groups in recent years.')I seems to be a hopeful synthon because of the reactive imidate group included in its str~cture.~'In this paper we wish to report a simple one-pot synthesis of 4(3H)-quinazolones and quinazolines having propionic acid at ~-~o s i t i o n ~) from I and o & carbonyl aniline derivatives.As the reported examples5), we observed that the reaction of various amines (11) with I yielded keto-amidines (111) in satisfactory yields.The physical and s p e c t r a l p r o p e r t i e s of I 1 1 are summarized i n Table 1.T h i s s y n t h e t i c method o f 111, which seems t o be an usual one, i s s u p e r i o r t o t h e former ones, f o r instance, t h e p a s t s y n t h e t i c methods o f 5-amino-~ll(~)-pyrrolin-2-one ( I I I a ) need t h r e e steps 8 ) from ethy1,R-bromopropionate7), two steps from s u c c i n o n i t r i l e and l i q u i d ammonia , and one step from s u c c i n o n i t r i l e and 1,1,3,3-tetramethylbutyl hypoperoxide. 9)By our method, t h e j u s t m i x i n g o f t h e EtOH s o l u t i o n o f I ( 1 eq mol) and t h e concent r a t e d aqueous ammonia (28%, 1.1 eq) i s s u f f i c i e n t t o g i v e t h e pure s o l i d ( I I I a ) .I n t h e cases of a n i l i n e d e r i v a t i v e s ( I I h , 111, IIj, and I I k ) having t h e e l e c t r o nwithdrawing groups a t ortho p o s i t i o n , t h e r e a c t i o n s i n EtOH were v e r y slow a t room temperature (Table 1) and lowered y i e l d s a t r e f l u x temperature.However, no s o l v e n t -c o n d i t i o n a t elevated temperature (80-140') overcame t h i s disadvantage and gave good r e s u l t s .From above observation, a simple one-pot r e a c t i o n of quinazolones and quinaz o l i n e s ( V I ) was attempted and accomplished.The t y p i c a l procedure employed was 0 as f o l l o w s : A m i x t u r e of 1 ( 2 mmol) and I I i ( 2 mmol) was heated a t 130-140 (bath ' 98, IR 1710, 1690, 1630, NMR(d6-DMSO) 2.30(2H,m), 2.6O(ZH,m), L l H,bi UV 231, M 112, IR 1720, 1660, 1600, NMR(d -OMSO) 2.3(2H,m), 2.55(2H,m), 2.80(9~,dj, 8.4(1H,b) UV 234, M 188, IR 1700, NMR(d6-DMSO) 2.3(2H,m), 2.6(2H,m), 4.25(2H, d), 7.23(5H,s), 8.$(lH,b) UV 212, 278, M 204, IR 1700, 1630, NMR(d6-DMSO) 2.4O(ZH,m), 2.80(2H,m), 3.70( 3H,s), 6+90(2H,d), 7.85(2H,d) UV 203, 264, M 217, IR 1760, NMR (d -OMSO) 2.50(2H,m), 2.80(2H,m), 7.g(3~,m), 7.8(2H,m) I UV 223, 272, 282, 290, M ' 241, IR 1715, 1690, NMR(d6-DMSO) 2.2-2.7(4H,m).Z.gO(2H.t).3.55(2H,m).6.80-7.60 , , , , , , , ., 66, IR 1700, NMR(CDC13) 11.70(6~,s), 2.70(4H,m), 3.50(2H,m ) , 90(2H,m) 239, M 126, IR 1700,1660, NMR I (CDC1,) 2.65(4H,m), 3.10(3H,s), 3.24a) The reaction time for the reaction in EtOH at room temperature is lisrpd.This is not always an optimum con$'tion.b) gY (Amax, EtOH, y), IR (KBr, cm ) , PMR (ppm).c ) lit. 227-230(dec) j, 250(dec] , 238-240(dec)