ALUMINUM CHLORIDE-CATALÏZED REACTIONS OF PHENOLS WITH HEXACHLOROPROPENE DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University by SIDNEY SCHIFF, B.S., M.S. The Olio State University 1958 Approved by Adviser Department of Chemistry ACKNaJLEDGMENT I vish to express sincere appreciation to Professor Melvin S. Nevman for his enthusiastic interest, his helpitil advice and his constructive criticism throughout the course of this investi­ gation. I would also like to thank my wife for her constant encour­ agement, confidence and sacrifices. IX TABLE OF CONTENTS INTRODUCTION 1 BACKGROUND 4 DISCUSSION OF RESULTS 38 I, Previous Work by Pinkus 38 II. Determination of Structure of I 4-0 III. Study of Reaction Conditions for Preparing 4& 3,4-Dichlorocoumarins IV. Reaction of Hexachloropropene with Other Phenols 48 V. Mechanism of Goumarin Formation 55 VI. Reaction of 3,4-Dichlorocoumarin with Bases 64 EXPERIMENTAL I. Generalizations 69 II. Structure Determination of 3,4-Picbloro- 71 6-methylcoumarin III. Reaction of Other Phenols with Hexachloropropene 75 IV. Reactions of 3,4-Dichlorocoumarins with Bases 85 SUMMARI 90 FIGURES 92 AUTOBIOGRAPHY 96 iii INTRODUCTION The present work originated from a study^ made on the reaction 1 , A. G. Pinkus, Ph. D. dissertation. The Ohio State University, 1952; hereafter referred to as "Pinkus dissertation. " of phenols and polyhalogenated compounds in the presence of aluminum chloride as a catalyst. This reaction, called the Zincke-Suhl reac- o tion, yields A-methyl-A-trichloromethyl-2 ,5-oyclohexadienone. 2. T. Zincke and R. Suhl, Ber., Al^S (1906). Mfu CXfl 3 [O] OH C In his study, Pinkus attempted to react phenols with other com­ pounds, such as benzotrichloride and 1 ,1 ,1-trichloroethane, containing the trichloromethyl (001^-) group. One of the compounds available at this time was hexachloropropene. From the reaction of p-cresol with hexachloropropene,3 there was obtained a goodly amount of light gray, 3 . A. G. Pinkus, private communication. amorphous material. From this could be isolated sharp-melting color­ less crystals. The results of several qualitative tests led Pinkus 1 to consider either 2 ,3-dichloro-6-methylchromone (1 ) or 2-dichloro- methylene-6-methylco'ujnarin-3-one (2 ) as the most probable structure for the compound. 1 The present study was initially concerned with definitely es­ tablishing the structure of the unknown compound. The structure was deduced to be 3,4-dichloro-6-mothylcoumarin (I) and an unam- Ul I biguous synthesis of 3 ,4-dichlorocoumarin verified the coumarin structure. After elucidating the structure of the product, a study was made to determine the optimum conditions for running the reaction. £-Chlorophenol was used as the substrate in this study because the purification of the product was easier tlian when p-cresol was used. Simultaneously, a study was made to extend the reaction to other substituted phenols because 3,4-dihalocoumarins have never been reported in the literature. The reaction of 3,4--âichloro-6-methylcoumarin vjith organic bases was investigated. The 4-chlorine was found to be the more reactive, but the 3-chlorine will react with difficulty. BACKGROUND I. ALUMimJM GHLORIDE-CATAIÏZED REACTIONS OF PHENOIS WITH TRICHLORO­ METHYL C0I4P0UNDS A, Reaction of Carbon Tetrachloride and Phenols The initial discovery that trichloromethyl compounds will react with phenols was made when bromination of 3,5-dichloro-p-cresol was attempted in carbon tetrachloride in the presence of aluminum.^ The 1 . T. Zincke and R. Suhl, Ber., 22» 4 M 8 (1906). carbonate of 2,6-dibromo-3,5-dichloro-p-cresol (A) was obtained in­ stead of the anticipated 2,6-dibromo-3,5-dichloro-p-cresol (B). ce. ct ov\ M o M o-c— 0 WTien B was treated with aluminum clfLoride in carbon tetrachloride, A was obtained. VJlien p-cresol was brominated in carbon tetrachloride id.th aluminum chloride present, a mixture of a 26 per cent yield of the tetrabrorao-p-cresol (C) and a 50 per cent yield of the carbonate ester (D) was obtained. When C was subjected to the same reaction conditions. Brv P rv o-co— o Q Brv the intermediate E was isolated. B v -CUL 13 iv E 3 The results of the Zincke-Suhl reaction which are most important in their relationship to the present work were obtained when £-cresol was treated with carbon tetrachloride and aluminum chloride. A AO per cent yield of a cyclic ketone, which was shown to be A-^ethyl-A-tri- chloromethyl-2,5-cyclohexadienone (F), was obtained. In a later study of the Zinke-Suhl reaction, the yield of this reaction was increased to 60 per cent.^ 1. M. S, Nevman and A. G. Pinkus, J. Org. Chem., !£, 978 (1954). On the basis of products isolated in their study, Zincke and Suhl proposed the existence of the trichloromethyl ether of p-cresol as an M&/ CC2-5 I I OH O intermediate in the reaction.^ Two other Intermediates, (G) and (H), 1 . T. Zincke and R. Suhl, Ber,, 22; 4148 (1906). Ob oH II H were later proposed,^ 2, K, kvMers and W. Julicher, ibid.. $5, 2167 (1922), On the basis of the latest work,^ the following reaction mechanism 3, M. S. Newman and A. G, Pinlois, J. Org. Chem., 12,, 978 (1954). was formulated. Aluminum chloride and p-cresol first form the dichloro- aluminum-p-cresolate salt, of which the p-cresolate ion can be written in the three resonance structures pictured. The trichloromethyl M ® r\ J K ketone is obtained by reaction^ through K. 1. For the sake of simplicity, the monomeric structure will be used for aluminum chloride, although it probably exists as a dimer. f ; b - 5 ^ + a.aî-cfl-3 O A c e ^ Reaction through J was postulated as the cause of the large amount of polymer that formed during the reaction. An attempt was made to force the reaction to occur more completely in the angular position by using 2,6-dibromo-p-cresol in the r e a c t i o n . ^ However, only a 9 per cent 2. M. S. Newman and A. G. Pinlcus, J. Org. Chem., 1^, 978 (1954). yield of the desired ketone was obtained, along with two other products which were not investigated. No dark polymer was obtained, however. The analogous reaction with 2 ,6-dichloro-2-cresol yielded 36 per cent of 2,6-dicliloro-4-methyl-4-trichloromethyl-2,5-cyclohexadienone, along 8 with a large amount of unreacted cresol. Again, no dark polymeric material was obtained, nor were there any by-products found as in the case of 2 ,6-dibromo-p-cresol. B. Reaction of benzotrichlorides and phenols The reaction of phenol with other trichloromethyl compounds was studied. VJhen benzotrichloride was used,^ and the reaction mixture 1. M. S. Newman and A. G. Pinlcus, J. Org. Chem., 985 (1954). was hydrolyzed with water, the expected Zincke-Suhl product (L) was not obtained. Instead, the dioxocin (M) was isolated in 29 per cent yield. %drolysis of the reaction mixture with calcium carbonate and ice instead of with water or acid resulted in 2-hydroxy-5-methylbenzo- phenone in 76 per cent yield. No dioxocin was obtained. The same results were obtained by using absolute methanol instead of water. In addition, a small amount of 2 ,b-dibenzoyl-^-cresol was isolated and identified. The alxnnlnum chloride-catalyzed reaction of phenol and benzo­ trichloride produced only ^hydroxybenzophenone in 90 per cent yield. When 2-chlorobenzotrichloride was reacted with p-cresol,^ a 1 . M, S. Newman and A. G. Pinkus, J. Org. Chem., 2^, 996 (1954). 19 per cent yield of 2-methylxanthone (N) was obtained in addition O OK ÜL Q Q N to a 17 per cent yield of the dioxocin and a 35 per cent yield of 2 '-chloro-2-hydroxy-5-methylbenzophenone. The xanthone was absent when the reaction was run in benzene. The dioxocin, the hydroxybenzophenone and the xanthone were all obtained when the reaction was run with 2 ,4-dichlorobenzotrichloride. The yields were, respectively, 32 per cent, 22 per cent, and 11 per cent. When 3,4-dichlorobenzotrichloride was used, no xanthone was possible, since cyclization to a xanthone requires a chlorine in the 2 ’ position. In addition to isolating a dioxocin in 9 per cent yield and a hydroxybenzophenone in 57 per cent yield, a 2 ,6-dibenzoyl-£- cresol was obtained in 14 per cent yield. 10 The formation of the xanthones and o-hydroxybenzophenones in­ dicates that reaction can occur through J, C. Miscellaneous Reactions of Trichloromethyl Compounds and Phenols In the study made by Nevman and Pinkus,^ g-cresol and 1,1,1- 1 , M. S. Newman and A. G. Pinlcus, J. Org. Chem,, 3^, 978 (1954). trichloroethane were reacted in carbon disulfide. A 1.6 per cent yield of the expected Zincke-Suhl product was isolated from the dark polymer which formed on hydrolysis. Mii, + C d j - C H 3 > II O In another study,^ trichloroacetonitrile and phenol were reacted 2. J. Houben and W. Fischer, J. prakt. chem., 123. 262 (1929). with aluminum chloride in chlorobenzene to afford trichloromethyl 2“ hydroxyphenyl ketone (O). No yield was given. OH OH 0 11 In a different study, the cyanohydrin of chloral was reacted 1. A. Chwala and H. Wassmuth, Monatsch., 81, 84.3 (1950). with phenol in the presence of aluminum chloride to afford j^-hydroxy- phenyl trichloromethylacetic acid (P) in 60 per cent yield. The same product was obtained in 42 per cent yield by starting with anisole. '"O C0.,CH(0H)C,N M a CH-COOM cce.^ P 12 II.