September 1969
947
SOTES
TABLE I:
P E N D A D I E N O I C A N D -DIYP;OIC
ACIDSA N D AMIDES A N D RELATEDC O h l P O C X D S R3
I
RlRsC=CH-CH=C-COX
x
NO.
Yield,
%
MU, O C
.inalysesc
a
43
Oil 190-19.i 145-150
N(n-CeH13)z
34
65-60:
0
37
164- 170
C, H,
32 13 14 38 9 21 41 25 14 10 40 91 61 .J6 66 40 ( 5 )
153-191 Oil 165-19j 112-128 160-172 Oil Oil 174-1 80
C, C, C, C,
203-208 17.5-179 260 dec 172-174 152 5-1.5.5 185-180 186-190
C, H, S C, H, S
22
.1 i
223-224
C, H, N
23
72
159-163
C, H, X
24
38
117-127
C, H, S
N (n-Pr)z SHCsHj
1 2 3
4 )
6 7 8
2-Naphthyl
H
%Fury1
H
OH
H
OCH3 NEtz NHz OH
9
10 11 12 13 14 13 16 17 18 19 20 21
OH NEtz OH NEtz
,i-Nitro-%f uryl
SHz j-Nitro-2-thieiiyI
H
H
NEtz OH OCH, NEtz NH (i-Pr) OCHx
32 36
C, H, N C, H, 1; C, H, K C, H, N pu'
H H, K H H, S U
C, Ha C, H, N C, H, S b
C, C, C, C,
H, N H, S H, S H, pu'
Oil 28 C, H 19 157 dec C, H 18 Oil C, H, S Thebe authors report mp 22-23' for 11. * Kyorin Pharmaceutical a R. J. Rallings and J. C. Smith, J . Chem. SOC.,618 (1953). Values within 3~0.470of theoretical were obtained for Co., Ltd., British Patent 982,730 (1965); Chem. ilbstr., 62, P14633u (1965). all analyses indicated. 25 26 27
the most active member of the previous series, extended the survival time of P . bwghei infected mice in the assay beyond 0.5 day at the 640-mg/kg level. X o toxicity was observed at the 640-mg/lig level. The preparation of the bis(p-chlorophenyl) series (1-5) has been given previously.2 The a-methyl compound 6 was prepared via the addition of carbethoxyethylidenetriphenylphosphorane to 3,3-bis(p-chlorophenyl) acrolein followed by hydrolysis. The acrolein mas derived from lithium acetylide addition to the benzophenone followed by acid-catalyzed rearrangement of the resulting carbinoL2 Compound 8 was prepared as a mixture of geometrical isomers from the Reformatsky reaction of p-naphthaldehyde with y-bromocrotonate according to the general procedure of Miller aiid K ~ r d . ~ The nitrothiophene ester 18 was prepared by treatment of 3-(3-nitro-2-thienyl)acrolein8 with carbometh( 7 ) R. E. Miller and F. F. Nord, J . Org. Chem., 16, 1720 (1951). (8) G. Carrara, R . Ettore. F. Fava, G. Rolland, E. Testa, and A. Vecchi, , I . Am. Chem. Soc., 76, 4391 (1954).
oxymethylenetriphenylphosphorane. Acid 17 was obtained from ester 18 by ester interchange in H2S04HOhc solution. The corresponding S-methylpyrrole ester 21, prepared both by addition of the ylide derived from methyl y-bromocrotonate to 1-methyl-5-nitropyrrole-%aldehydeg (5% yield), and by treatment of 1-methyl-5-nitropyrrole-2-acroleing with carbomethoxymethylenetriphenylphosphorane (40% yield), could not be hydrolyzed. The K-methylnitropyrrole acrylic acid 22 wa3 formed by a Doebner reaction 011 1-methyl-5-nitropyrrole-2-aldehyde. The diacetylenic acids were prepared by the Cu(1)catalyzed coupling of 3-bromopropiolic acid with phen$acetylene and p-fluorophe~iylacetplene.~~~~ All of the dieiioic acid amidez were ol,t:iincd by thc mixed anhydride method, and the diyiioic acid amideby in situ diethylamine treatment of the acid chlorides which had I ~ e i igcueraircl I)! lh(t w t l i u i r i 5:71t- o u l \ 1 chloride method. (9) P. Fournari, Bull. Soc. Chzm France, 488 (1963) (10) W. Chodkienicz, A n n Chnm. (Paris). 2, 819 (1987).
