May 20, 19.33
NOTES
2.725
tubes were also examined by infrared spectroscopy to con- hydroxide and can be recovered by the addition of firm the identities of the materials present.16 acid. COLLEGEOF PHYSICIANS AND SURGEONS Attempts to reduce the sulfonyl chloride to wDEPARTMENTS O F BIOCHEMISTRY AND O F acetophenonesulfinic acid by conventional methods OBSTETRICS AND GYNECOLOGY failed. Friedel-Crafts reactions with the sulfonyl COLUMBIA chloride were unsuccessful due to the decomposition NEWYORK32, N. Y. of that substance with the evolution of sulfur dioxMEDICALLABORATORIES OF THE COLLISP. HUNTINGTON MEMORIALHOSPITALOF HARVARDUNIVERSITY AT THE ide. MASSACHUSETTS GENERALHOSPITALAND THE DEPARTIn an attempt to obtain a more stable P-ketosulMENT OF BIOLOGICAL CHEMISTRY OF HARVARD MEDICAL SCHOOL26,28
BOSTON14, MASS. (25) The Perkin-Elmer Model 21 double beam infrared spectrophotometer was used. (26) This work undertaken independently and simultaneously in the Columbia and Harvard laboratories is published here jointly. (27) This work was supported in part by gifts from the Squibb Institute for Medical Research and the Damon Runyon Memorial Fund. (28) This is publication 782 of the Cancer Commission of Harvard University. This work was supported in part by an Institutional Grant from the American Cancer Society, Inc., to the Massachusetts General Hospital and in part by a grant from the National Cancer Institute (U. S. Public Health Service).
fonyl chloride, isobutyrophenone-a-sulfonylchloride was synthesized. Isobutyrophenone- a-sulfonic acid was prepared by the dioxane-sulfotrioxide method, and the sulfonyl chloride was prepared by means of phosphorus trichloride. These two substances were found to be much more stable than the analogous derivatives of acetophenone, e.g., isobutyrophenone-a-sulfonicacid has been stored in a paraffin sealed bottle for a year with little apparent change. Despite its greater stability, attempts to reduce the sulfonyl chloride to the sulfinic acid and to carry out Friedel-Crafts reactions with it met with failure.
Experimental9 wAcetophenonesulfony1 Chloride.-Acetophenone (159 g., 1.34 moles) was added to 1.34 moles of the dioxane sulfoBY WILLIAME. TRUCE AND CALVIN W. VRIESEN~ trioxide reagent6 in 400 ml. of ethylene chloride. The reaction mixture was cooled with an ice-bath, whereupon the RECEIVED JANUARY 7, 1953 sulfonic acid separated out. The product was removed by The conversion of a /3-ketosulfonic acid or its salt filtration and placed in a vacuum desiccator for three hours. to the corresponding sulfonyl chloride does not ap- A portion of the acid was recrystallized twice from ethyl m.p. 75-78', lit.8J0 73-75', 77-78'. The crude pear to have been reported previously. The action acetate; acid and 361 g. (2.62 moles) of phosphorus trichloride were of clilorosulfonic acid on acetophenone produced the heated on the steam table under gentle reflux for 14 hours. 2,w-disulfonyl chloride, while acetophenone-4-SUI- The excess phosphorus trichloride was removed a t a water fonic acid with chlorosulfonic acid probably formed aspirator and the product was recrystallized from chloroconversion 122 g. (42% of theory), m.p. 87.5-88.2'. the 4,w-disulfonyl ~ h l o r i d e . ~Treatment of sodium form; Dry ammonia was passed into an ether solution of ww-acetophenonesulfonatewith the same reagent re- acetophenonesulfonyl chloride until the ammonia odor persulted in the 2,w-disulfonylchloride.s The prepara- sisted. The resulting product was recrystallized from ethtion of y- and 8-ketosulfonyl chlorides has been ac- anol; m.p. 158-159'. Anal. Calcd. for CsHgOaNS: N, 7.04. Found: N, 7.02. complished by conventional method^.^^^ Thirteen grams (0.060 mole) of w-acetophenonesulfonyl When sodium w-acetophenonesulfonates was chloride was dissolved in 46 g. (1.0 mole) of absolute ethtreated with phosphorus pentachloride or phos- anol. Heat was liberated and after an hour the solution phorus oxychloride, charring occurred. The free was cooled with an ice-bath, whereupon crystals of the prodsulfonic acid was then prepared by a modification of uct separated out; conversion 9.0 g. (64% of theory), m.p. 44.5-45.5' after recrystallization from petroleum ether. the procedure of Truce and Alfieri6 Separate por- The neutral equivalent was obtained by titrating an alcotions were immediately treated with phosphorus pen- holic solution of the ester with standard aqueous sodium tachloride, thionyl chloride, or phosphorus oxychlo- hydroxide solution to a phenolphthalein end-point ; calcd. ride, but charring occurred in all cases. However, 228; found, 229 and 227. Calcd. for CtoHlpOrS: C, 52.62; H , 5.29. Found: treatment of the acid with phosphorus trichloride,? C,Anal. 52.88; H, 5.29. resulted in the formation of o-acetophenonesulfonyl Isobutyrophenone-cu-sulfonyl Chloride.-Using the same chloride. The sulfonyl chloride was found to be procedure as previously described, 84 g. (0.57 mole) of is+ too unstable to be submitted for analysis; it was butyrophenone (b.p. 217-220' (746 mm.)) was converted to necessary to prepare the sulfonamide for that pur- 81 g. (63% of theory) of isobutyrophenone-cu-sulfonicacid. portion of the acid was recrystallized from ethyl acetate pose. The instability of the free acid and the sul- A and melted a t 69.5-72.0'. fonyl chloride is probably due in part to the activIsobutyrophenone-cu-sulfonicacid (51 g., 0.22 mole) and ity of the methylene g r o ~ p . The ~ activity of 21 g. (0.15 mole) of phosphorus trichloride were heated on the methylene group is further demonstrated by a steam-bath overnight. The reaction mixture was decomwith ice water and extracted with chloroform. After the fact that the ester, ethyl w-acetophenonesul- posed drying over sodium sulfate, chloroform was removed by disfonate, can be dissolved in dilute aqueous sodium tillation and the resultant yellow oil was taken up in boiling petroleum ether. White needles separated out; weight 25 (1) An abstract of a portion of a thesis submitted by Calvin W. E. (44% of theorvl. m a . 40.0-41.5°. Vriesen to the Faculty of Purdue University in partial fulfillment of dnai: Ca1cd.- for CIOHllCIOPS: C, 48.64; H, 4.49. the requirements for the degree of Doctor of Philosophy, August, 1952. Found: C, 48.75; H, 4.42. (2) Purdue Research Foundation Fellow. (3) A. W. Weston and C. M. Suter, THISJOURNAL, 61, 389 (1939). DEPARTMENT OF CHEMISTRY (4) S. Smiles and T. P. Hilditch, J . Chcm. Soc., 91, 522 (1907). PURDUE UNIVERSITY (5) F. S. Kipping and W. J. Pope, {bid., 68, 548 (1895). INDIANA LAFAYETTE, (6) W. E. Truce and C. C. Alfieri, Tms JOURNAL, 73,2740 (1950).
The Preparation of p-Ketosulfonyl Chlorides'
-
(7) W. A. Proell, C. F. Adams and B. H. Shoemaker, I n d . E n p . Chem., 40, 1129 (1938). ( 8 ) CV.D. Parkes and S . G . Tinnley, J . Chrm. Sac.. 1861 (1834).
(9) All melting paints are corrected. (10) W. von E. Dacring and F. hl. Beringer, T e r s 2221 (1040).
JOURXAL,
71,
