1d HOCH 2 CH 2 SSSCH 2 CH 2 OH R 1 NSSSN R 1 R 2 R 2 2 TETRAHEDRON LETTERS Tetrahedron Letters 42 (2001) 8607–8610 Pergamon Sulfur-atom insertion into the SS bond—formation of symmetric trisulfides Yihua Hou, a Imad A. Abu-Yousef, b Yen Doung a and David N. Harpp a, * a Department of Chemistry, McGill University, Montreal, Quebec, Canada H3A 2K6 b Department of Chemistry, American University of Sharjah, PO Box 26666, Sharjah, United Arab Emirates Received 17 September 2001; accepted 9 October 2001 Abstract—The reaction of triphenylmethanesulfenyl chloride (3a) with acyclic disulfides 4 or 5 give the respective trisulfides 1 or 2 in moderate to good yield and selectivity. A mechanism is advanced to explain the chemistry. © 2001 Elsevier Science Ltd. All rights reserved. Symmetric trisulfides have been found in many natural sources such as onions and garlic, 1 brown algae 2 and various animals. 3 Many of these trisulfides have signifi- cant biological importance. 4 A recent example is bis(2- hydroxyethyl)trisulfide 1d. 5 It was separated from Bacillus stearothermophilus UK563 and shows cyto- toxic, antitumor and immunostimulant activity. Another type of trisulfide, diamino trisulfides 2, can be used as crosslinking and accelerating agents in polymer- ization reactions in the rubber industry as well as in pesticides. 6 Symmetrical trisulfides have been prepared by the reac- tion of sulfur dichloride with thiols 7 wherein olefinic or hydroxylic functions cause side reactions. Trisulfides are usually obtained as mixtures of polysulfides by the reaction of alkyl halides with sodium trisulfide, 8 thiols with sulfur, 9 the reaction of sodium or potassium sulfide with alkanesulfenyl chlorides 10 and other meth- ods involving thiosulfonates. 11 A practical method for the synthesis of diamino trisulfides was reported by Katritzky employing the reaction of diamino disulfides with sulfuryl chloride, sodium sulfide nonahydrate and sodium hydroxide. 6 The method is applicable to bis(N,N -dialkyl- amino)disulfides or bis(N,N -diallylamino)disulfides with yields of the trisulfides ranging from 47 to 81%. However, N -aryl substituted aminodisulfides give poor results because of the reaction of the aromatic rings with sulfuryl chloride. As a continuation of our earlier studies on the reactions of chloro(triphenylmethyl)di- and trisulfide (3b and 3c) with symmetrical disulfides, 12 we have discovered that the reaction of triphenylmethanesulfenyl chloride 3a with acyclic symmetric disulfides 4 or 5 give the respec- tive trisulfides in moderate to good yield and selectivity. This reaction serves as an alternative method of prepa- ration of trisulfides using easily accessible disulfides. Chloro(triphenylmethyl)sulfide (3a) is commercially available 13a and can also be readily synthesized by the reaction of sulfuryl chloride with triphenylmethane thiol in ether 13b followed by recrystallization from chlo- roform and ethanol at room temperature; reagent 3a is stable in the freezer for years. It was also observed that heating it in chloroform solution caused its decomposi- tion. Its addition reactions with thiiranes and olefins have been studied. 14 The conditions of the reaction of 1a with dimethyl disulfide were optimized by temperature, rate of addi- tion, solvent and concentration of the reagents (Scheme 1). Quick addition of 1a at room temperature to the solution of disulfide turned out to be the most favor- able for the reaction. Much better yields and selectivity Keywords : disulfides; trisulfides; tritylsulfenyl chloride; sulfur inser- tion. * Corresponding author. Tel.: 1-514-398-6685; fax: 1-514-398-3797; e-mail: david.harpp@mcgill.ca 0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved. PII:S0040-4039(01)01897-4