September 196s
1073
SOTER
TABLEI1 2 - A M I N n E T H . i ~ E S v L F O N . ~ ~ I L I D E(T') S
No.
x, Y
Yield punned, Mp,
70
O C
Vb 4-C1 160-162a 66 VC 3,4-C1, 157- 139 64 VJ 3-CF1 134-136 3 1.e 4-CF3 163-167 76 262-263 der 44 \'i 3 , ,?-( CFa)? c1.g 4-SCH3 162-16.5 \h 4-0CIT2c61Ij 211-214 94 a Lit.6 mp 160.3-161.5". These intermediates were riot analyzed. next step. Free base, mp 178-181".
I
HOCH2-C-CHOHCONH(CH2)2S02NH
I
CH? SO.
x. Y
TIb 4-C1 TIC 3,4-C12 \ Ie 4-CF3 VIg 4-SCHa T Ih 4-OCH2CsHj Lit.6 mp 101-103° c 1, 95yo EtOH.
Mp, " C
103-104h 141-143 144-146 112-1 14 142-144 from C6fI6.
Yield purihed.
Purifn
L?c
so11 ent
.j9
C6156 CHCL
[m]23D,'c
der
Formula'
+40
CI4H,iC1?;,OaS C14H&l?K,O,S Ci,H,iF,NzO,S Cl ,Hu?;jO,S2 CPIHBS?OBS
+ + +
38 66 43 Hz0 36 67 cicrtcEr,ci +40 28 ClCII,CH,Cl 33 compounds weie analvLed for C, H, N.
Escherichia coli (T'ogel), Streptococcus pyogenes (C203), Proteus mil-abilis (ALGH-l), Salmonella typhimuriunz (V-31), and Shigella son?zei (C-10). Among them, VIh suppressed T . vayinalis i n viti.0 a t a concentration of 25 pg/ml and completely inhibited the growth of S. ~ J O qenes ((3203) a t 1.25 pg/ml. Experimental SectionlSrl9
+
D-( )- 2,4 -Dihydroxy- 3,3-dimethyl-N- [2-(phenylsulfamoyl)ethyllbutyramides (VI, Table III).-A mixtiire of 0 Old mole of the reqiii4te 2-aminoethanesiilfonanilide (I-)and 3 9 g ( 0 03 mole) of D-( -)-pantolactone was heated in a melt at 100-ll.io for 2 hr The melt was cooled and crystallized from the rolvents indicated.
Acknowledgments.-The authors are indebted to Dr. Leo Rane of the University of AIiami and to Dr. Paul E. Thompson and Dr. AI. W. Fisher of Parke, Davis and Company for the biological testing. We also wish to thank A h . C. E. Childs and associates for the microanalyses, and Dr. J . AI. Vandenbelt and coworkers for determination of the spectral data reported herein.
1,3-Dioxo-2-isoindolineethanesulfonic acid monopotassium salt (11) was prepared by the method of IIiller and Roblinh11 in 83YGyield. 1,3-Dioxo-2-isoindolineethanesulfonylchloride (111) was obtained from I1 by the method of Miller and Roblin6111 in 80% yield, mp 158-162'. 1,3-Diox0-2-isoindolineethanesulfonanilides (IV, Table I).To a stirred solution of 0.1 mole of the substituted aniline in 75 ml of pyridine, cooled with an ice bath, was added slowly 30.1 g (0.11 mole) of 1,3-dioxo-2 .isoindolineethanesdfonyl chloride Derivatives of 5-Phenyl-2,4-pentadienoicAcid (111). After the reaction mixture was stirred for 1 hr with cooling, the ice bath was removed and stirring was continued for 1.25 hr. as Potential Antimalarial Agents' The reaction mixture was poured into 500 ml of H2O with vigorous stirring, and the crude product was isolated by filtration. ReLESLIE31.WERREL,N ~ S C YHE \DEN, crystallization from glacial or dilute AcOH gave the product. .WD EDW IRD F. E L S L ~ G E R 2-Aminoethanesulfonanilides (V, Table II).-A mixture of 0.02 mole of the appropriate 1,3-dioxo-2-isoindolineethanesulfonR w a r c h Laboratories, Parke, Davis and Company, anilide, 1.2 g (0.02 mole) of 85% hydrazine hydrate, and 100 ml Ann Arbor, Mzchzgan 48106 of EtOH was heated imder reflux for 3 hr. The reaction solution was homogeneous when refluxing began, but after 15 min a Received dfay 9, 1968 precipitate appeared. The mixture was concentrated to dryness and the residue was suspended in 200 ml of H,O and made acidic to congo red with 4 .V HCI. This slurry was heated on a The reported effectiveness of 5-(p-chlorophenyl)-Ssteam bath for 10 min, cooled in an ice bath, and filtered. The isopropy1-2,4-pentadienaniide (Ia) against Plasnzodiunz filtrate was neutralized with concentrated ?;H,OH to give the gallinaceunz in the chick2 prompted the synthesis of prodiict. The compounds were recrystallized from the indicated solvents when neceesary. (18) Melting points (corrected) mere taken in open capillary tubes in a Thomas-Hoover capillary melting point apparatus. (19) IVhere analyses are indicated only Iiy symbols of t h e elements or functions, analytical results obtained for those dements or funrtions were witliin r0.4yoof tlie theoretical values.
(1) This investigation v a s supported by t h e U. S.Army Medical Research and Development Command under Contract DA-49-193-.\ID-2754. This is Communication S o . 382 to tlie Army Research Program on 1Ialaria. (2) G . R. Coatney, W.C. Cooper, N. B. Eddy, and J . Greenllerp, "Survey of Antimalarial .%gents," Pulilic Health Service Pullliration No. 193, \Vasl~ington, D . C . . 1953, p p 98, 134, 262, 2 i G .
