BENDICH A N D ERWIN CHARGAFF
1568 [CONTRIBUTION FROM
THE
BIOCHEMISTRY, COLLEGE
DEPARTMENT OF
UNIVERSITY 1
Yol. 65
OF PHYSICIANS AND SURGEONS, C O L U ~ ~ B I A
Synthesis of 2-Methyl- 1,4-naphthoquinone-8-sulfonicAcid' BY
AARON
BENDICHAND ERWIN CHARGAFF
The oxidation of a naphthalenesulfonamide to In the course of work on the coagulation of fibrinogen by quinones, t o be presented else- the corresponding a-naphthoquinonesulfonamide, where,:! it appeared of interest to examine 2- as briefly presented here, is perhaps of more genmethyl 1,4 -naphthoquinone 8 sulfonic acid. eral importance since it may lead to compounds There exist no general methods for the intro- of chemotherapeutic interest. A study of the duction of a sulfonic acid radical into the vitamin K activity of 2-methyl-l,4-naphthoquibenzenoid portion of 1,.l-naphthoquiiione. The none-&sulfonic acid will be presented a t a later literature, in fact, contains only- two examples of date.6a compounds of this type, 1.4-naphthoquinone-6Experimental sulfonic acid3 arid its 2,3-dichloro derivative,4 2-Methylnaphthalene-8-sulfonicAcid.-The procedure both of which were obtained bv methods of very used, a modification of that of Veself and PBE,5 yields a limited applicability. mixture of 2-methylnaphthalene-1- and 8-sulfonic acids Attempts to prepare the desired substance by which are separated by fractional crystallization of the direct sulfonation of 2-methyl-l,4-naphthoqui- barium salts. To 200 g. of 2-methylnaphthalene in 270 cc. of carbon tetrachloride a t -lo", 93 cc. of chloronone with chlorosulfonic acid or by the oxidation sulfonic acid was added dropwise with mechanical stirring of 2-methylnaphthalene-8-sulfonic acid5 in acetic ill the course of forty minutes. The mixture was kept acid with hydrogen peroxide or chromic acid were a t -1U" for three hours and a t room temperature for unsuccessful. In the latter case sniall amounts fifteen hours, and then poured onto 1400 g. of crushed of 2-methyl-l,4-naphthoquinonewere isolated, ice. To the aqueous phase, following two extractions with 300-cc. portions of carbon tetrachloride, 165 g. of barium which indicated that partial hydrolysis of the sul- carbonate was added a t the boiling point and the hot mixfonic acid had taken place during the reaction. ture rapidly a t e r e d through diatomaceous earth on a hot The oxidation of 2-methylnaphthalene-8-sulfonyl buctiori funnel. After cooling of the filtrate in the rechloride with chromic acid likewise failed to yield frigerator overnight, the crude barium salt that had separated was recrystallized from 700 cc. of water in the products of sufficient purity. presence of Norite, when 200 g. of pure barium 2-methylThe method that was finally found to give satis- naphthalene-8-sulfonate (dried a t 120") was obtained factory results consisted in the oxidation with (49y0 of t h e theoretical yield). The treatment of the chromic acid of 2-methylnaphthalene-8-sulfon- solution of the barium salt with the required amount of amide to the corresponding naphthoquinone- potassium sulfate followed by the evaporation of the sulfonamide, followed by the conversion of the filtrate and drying a t 120" gave the potassium salt in a yield of 97%. latter to the sulfonic acid with nitrous acid. 2-Methylnaphthalene-8-sulfonyl Chloride.-The chlori-
- -
-
S02NH2
SO2NH2 0
-C"
HNOi
---+
0 I___.--
(1) This work has been supported by a grant from t h e John a n d Nary R. Markle Foundation. (2) E. Chargaff and A. Bendich, J . B i d . Chem., in press (3) F. Fabrowicz and W. LeBniaiiski. Roceniki C h e w . . 11, 636 $1931); Chem. A h . , 26, 3791 (1932). (4) A. Claus and S. van der Cloet, J . pvakl. Chem., 37, 181 (1888) (5) V. Veseli. and J . Phi., Coli. Czech. Chrm. CummiLtL, 2, 471 11830).
iiatioii was carried out according to the procedure of Steiger.G An intimate mixture of 174 g. of finely powdered potassium 2-methylnaphthalene-8-sulfonate and 348 g. [if phosphorus pentachloride was, after liquefaction had occurred, heated on the steam-bath for one-half hour. After addition of 1300 g. of crushed ice, the cooled mixture was kept a t 0" for twenty hours and the sulfonyl chloride5 filtered off and dried. It weighed 145 g. (90% of the theoretical yield) and melted a t 94-95' after crystallization from 80% acetic acid. 2-Methylnaphthalene-8-sulfonamide.-The treatment of 74 g. of the finely powdered sulfonyl chloride with 600 cc. of concentrated ammonia on the steam-bath for forty minutes, followed by dilution with 1liter of water, resulted in the separation of the sulfonamide6 weighing 66 g. (97% .
.
(5,) According t o a private communication from Dr. H. Dam of the School of Medicine, University of Rochester, this compound e r hibited an extremely low vitamin K activity (less than 1/1000 01 that of menadione), when assayed in chicks. 61 l i . 13. Stciger, Helo. C h i r u .%
