Journal of Xedicinal Chemistry, 1970, I-01. 13, .Yo. 3 569
NOTES
obtained by the reductive methylation of 3-nitrophthalic acid followed by thermal dehydration. The CO ir stretching frequencies of the naphthacenequinones are listed in Table I. There is a marked lowering as a result of the substitutions in the molecular environment. This shift is consistent with that observed in the related hydroxy quinone^,^ hydroxyiiaplitlioquinones,j and hydroxyanthraquinones.6 The uv data listed in Table I reveal the bathochromic shift upon the introduction of the substituents adjacent to the quinoid nucleus of the naphtliaceiiequinones. This shift is also in agreement with the reported findings for hydroxnaphth~quiones~and hydroxyanthraquinones.8 Biological Results.-The oral LDjo of 3c, d, and e , as determined in mice, was >2000 mg/l4000 mg;kg PO. Intraperitoneally the LD50 for 3c, d, and f were >2000, >2000, and >lo00 mg,/kg, respectively. Compounds 3c, d, e, and/or f shom-ed no significant activity against Diplococcus pueunio?iia type I,9Streptococcus pyogen^,^ Salnzonella ~chottiiiuelleri,~and Candida albicansg a t 500-1000 mg/kg PO. Compound 3c exerted marked activity against the solid form of Ehrlich carcinoma10 but was inactive against Sarcoma 1SO and Ehrlich ascites.'O Compound 3d demondrated a slight but definite activity against Sarcoma 1SO'O and Ehrlich solid carconomalO but was inactive against leukemia L1201 ascites.'O Compound 3~ x i s ineffective against Ehrlich ascites;'O 3f was appreciably active against Sarcoma 1SO'O and Ehrlich solid carcinoma.10 Experimental Section 1Ielting points were determined on an electro-thermal melting point apparatus and are corrected. Ir spectra were determined in KBr o n a Beckmari IR-3 double beam spectrophotometer with S a C l optics. C v ,spect,ra were determined in i-PrOH on a Cary spertrophotometer (Model 1411). Where analyses are indicated by the elements, results obtained were within +0.4% of the theoretical values. Since our main objective mras t'o obtain material for preliminary screening purposes, no attempt was made to optimize the yields. The properties of the naphthaceneqiiinoneq prepared are listed in Table 11. 1,4-Dihydroxynaphthalene (I).-A solution of 25 g of 1,4naphthoqliinone (Tech)" in 130 ml of IIMF was stirred and warmed gently with charcoal for 1 hr and filtered. The filtrate was hydrogenated under 3 atni of H2 over 0.5 g of PtO,, and the H2 uptake was rapid. After filtering the catalyst, the solution was evaporated t o dryness in vacuo irilder Ns. The residue was triturated with HsO, filtered, and recryst,allixed from boiling HyO containing a rmall amount of SnCl2 and HCl. Upon cooling, the prodrict was obtained as colorless glistening needles: mp 188-1(JOo; yield 20 g ( 7 g C ; ) . d n a l . (C,oH,O,) C, H. (4) -1.IV. Johnson. J . R . Quayle. T . S. Robinson, N. Sheppard, and .I, R . Todd, J . Chem. Soc., 2633 (1551). ( 5 ) 31. Jasien, K.Fuson. J . LelJas, and T. 31. Gregory, J . Chem. Phus., 21, 331 (1553). (6) I3. H . Howard and 1%.Raistrick, Biochem. J . . 59, 475 ( 1 9 5 5 ) ; 31. St. C. Flett. J . Chem. S o c . , 1441 (1548); H. Bloom, I,. H. Briggs. and B. Cleverl.-. ihid.. 178 (156Y). ( 7 ) R . .\. Morton and W.T. Earlam, ibid., 159 (1541). (8) H. Birkinshan; Biochem. J . . 69, 485 (1555); A. I. Scott, "Interpretation oE t h e Ultraviolet Spectra of Natural Compounds," Pergamon Press, Nrn. York. S . Y . ,1864, p 291. (5) E. Grunberg, J. Berger. G. Beskid. R. Cleeland, H. i'i. Prince, and E. Titswortli. Chemotherapia. 12, 2 i 2 (lQ67). (10) E. Grunberg. H. N. Prince, E. Titsrvurth, G . Heskid. and AI. D. Tendler. i b i d . , 11, 249 (1966). (1 1) Distillation Products Industries, Eastman Organic Chemicals D w a r t m e n t . Rochester, h-.Y . 14603.
-x
h
4
