+
1 (see Scheme I ) . 13ec>aiisethey cc~rit:~ili the Sc~iiiiioli~iol fwictioii these coiripoiuid, are chelatiiig ageiits, biit they are also iiierocyaiiiiies niid thris change color markedly with variations i i i solvent polarit)-, :I siihject, disciissed elsewhere.* All biit the first2 of the compoiiiids listed iii Table I :ire new; like most solvatochromic compomids they are iisiially ohtaitied as hydrates from solveiits voiitaiiiiiig water. 111 the screening program of tlie Caiicer C'heniotherap\, Nalional Service Ceiiter aeveral of ihcue compounds shelved CI)IIsiderable toxicity i i i vel1 ciiltiire test. (see Table II), biit testing :ig:tiiwt caiic-er iii other syslenis iiditi the roiltitie i n v1'uo screetiiiig cwifirlned toxicity biit iiidktied I 1 0 sipiiific:tiit activity. poiiiids s i i c h :is
I ) \$-erec.r,v~t:tllizctlf'roni ethaiiol iiisle:td, :iiid 4--6 were prep:ircvl without piperidine :I> wt:ilyst. Coiiipouiid 4 had t,v he preciliiiated by t h e addition of IICl atid ether to the reactioii tiiist,iue. Acknowledgment.---This work \vas supported iii part I)?. gr:ttit (C.4 074-03-02'i from the Sational Cancer Institute.
:I
Some Hydrazones of 3-Pheii;vl-B,4- thiazolidinedioiie
Experimental Section
Preparation of (I~ompounds.--Ci~tidetis~~tioii~ of 5-forniyl-Squinoliiiol with rnethiodides of appropriate heterocyclic itctive methyl compouiids gave a11 of the products described in this paper. A salutioii cr)ntainirig 0.02 mole of the aldehyde, 0.015 mole of ii rnethiodide, niid 1.5 tnl of piperidine iti 60 1111of 1propitino1 W:L refluxed for 1hr: o i i cooling, the urt, usually separated and w:w filtered, washed recrystallized from 80': nieth:uiol. Corripouiids 2 and 3 (T:ible
(hnipuiiiids haviiig structiires similar to the hydrazolies of 2ptieii~l-2,4-thi:tzolidiiietiione have exhibited aiititiiberciilons,3 .
sirart i n yarr f r o m the 13,s. The& of Peter .i. Ciavarri, .Jr. ( 2 ) 11. Taniyarna, S,Takcmrira. 13. Tiasui, and If. LTchiria, J . I'harm. bo,,. .la>m>i,1 4 , 113 f 1$1.5-I . ~
NEW COUPOVSDS
July 1966
643
T LBLE I SOME
HYDRAZOSES O F 5-PHETYL-2,4-THI.~ZOLIDINEDIONE O=C-NH { I C,H,-CH C=NN=R S '' LIP, O C
R
----%
Yield,
%
Formula
calcd----
H
C
C O S ( CeH:)N( CH,)C( CHd)=CCH=
259-260
90.02
C21H1&jOrS
CON(CeH;)N(CHa)C(CHa)=CNHCH=
254
56.00
C Z I H ~ O S ~ O ~59.99 S 4.80
19 99
CH~CH?OCHICH~NCH=
275
18.32
Ci4Hi6?ia01S
38.00 5.50
250
38.40
C17Hd40Sa
L
i
antianemia, and antithyroid a c t i o i ~ - ~Some 5,5-dialkyl derivatives possess hypnotic properties.7-10 The methods for the preparation of both the parent compoiindll and many of its derivatives are described iii l i t e r a t ~ i r e . ~ -12-15 ~ ~ s Four new analogs are listed in Table I.
found--H
7 %
S
C
S
62.21 4 . 7 2 17.28 62 52 4.90
17.01
59.42 5 07
20.10
14.50 57.81 4.94
14.79
57.95 3 . 4 3 15.90 57.20 3.98
15.81
tent neiirotoxic and convulsive activity in a "bteroidlike" molecrile, ~e iuidertook the synthezib aiid phy4ological evaluation of the heterocyclic portion of the alkaloid. K e suspected it to be responsible for the iiricommon activity.'
Experimental Section16 4-Formylantipyrine Hydrazone of 5-Phenyl-2,4-thiazolidinedione.-4-Antipyrine carboxylate (4.0 g, 0.02 mole) was dissolved in ethanol and made basic with NaOH. Thiosemicarbazide (1.8 g, 0.02 mole) was then added. After allowing the mixture t o stand for 10 min ethyl phenylchloroacetate (4.0 g, 0.02 mole) was added aiid the mixt'ure was shaken. Sodium acetate (1.6 g, 0.02 mole) and 6.0 ml of dilute acetic acid were then added and the mixture was refluxed for 30 min. Upon cooling a yellow crystalline solid was filtered off, air dried, and recrystallized from ethanol T h e hydrazones of S-formylaminoantipyrine, K-formylmorpholine, and 9-formylbenzythiazole Kere prepared and purified in the same manner. _ _ ~ (3) E. V. Vladeimirskaya, N . AI. Turkevich, Zh. Obshch. K h i m . , 26, 2150 (1955); Chem. Abstr., 60, 8605b (1956). (4) S . XI. Turkerich, E. V. Vladsimirskaya, Z h . Obshch. K h i m . , 24, 2010 (1954); Chem. Abstr., 49, 14737i (1955). (5) 3. M . Kapustyak, Farm. Zh., 14, No. 3, 6 (1959); Chem. Abstr., 66, 56501'(1961). (6) iV..\I. Turkevich, I
