Synthesis of DSP and DTBP

DSP 

A typical preparation of dithiobis-(succinimidyl propionate) can be accomplished as follows: to a solution of dithiodipropionic acid (105.15 gm, 0.5 M, MW: 210.27), http://www.sigmaaldrich.com/catalog/product/aldrich/109010?lang=en&region=US, 109010-250G $ 63.30

N-hydroxysuccinimide (115.09 g, 1.0 mole, Molecular Weight 115.09,  130672-100G, $91.30, 130672-250G, $247.50, https://us.vwr.com/store/catalog/product.jsp?catalog_number=200001-338, acros organics 250 g AC15727-2500 200001-338 $189.78)

in 600 ml of Tetrahydrofuran (360589-500ML, $74.20; 360589-1L, 97.90) at -5° C. was added dropwise a solution of 206.32 gm (1.0 m) of dicyclohexylcarbodiimide (D80002-100G, $55.00; D80002-500G, $191.00, NN'-DICYCLHXYLCARBODIIMID 500G

 N,N'-Dicyclohexylcarbodiimide Catalog Number: AAA10973-36 Supplier: Alfa Aesar, $108.71) in 100 ml of THF. The resulting reaction mixture was stirred at 0° C. for 24 hrs. After an additional 24 hrs. stirring at room temperature, the solid by-product, dicyclohexylurea, was filtered off and discarded. The filtrate was evaporated to dryness, taken up in ethyl acetate (270989-1L, $72.70, 270989-2L, $104.00) and the desired product precipitated by addition of hexane (296090-1L, $88.20). The product after drying is a white (yield - 90 g) powder M.P. 63°-5°. Further purification by recrystallization yields a product having a melting point of about 121°-123° C.

DTBP

Synthesis of 3,3'-Dithiobispropionitrile
10.6 g (44 mmol) of Na,S. 9 H z 0 and 1.4 g (44 mmol) of elemental sulfur were mixed and heated lightly until a clear reddish melt was obtained.
40 ml of cold water were added and the solution was chilled in an ice bath. 5.2 g (100 mmol) of freshly distilled acrylonitrile were added in portions with mixing and cooling. The mixture was stirred for an hour, taking care that the temperature should not rise above 25 "C, after which 160 ml of water were added and an oil phase was separated out. The water phase was extracted with three portions of ethyl acetate (or CHC13). The combined oil and ethyl acetate extracts were dried over anhydrous Na,SO, and evaporated, leaving 7 g of a reddish oil. Thin-layer chromatography (alumina, Riedel-de Haen AG, Seelze-Hannover) developed with CHClJpetrol ether ( l : l / v : v ) gave one major and two minor spots (visualized by exposure to I, vapour or ultraviolet light). The oil was dissolved in benzene, adsorbed on a column of neutral alumina (Woelm, grade 3, 200 g), and eluted batchwise with 250-ml volumes of petrol ether containing increasing amounts of methylene chloride (10% to 100% in increments of 10%). Each fraction was evaporated to dryness. Free sulfur emerged at the beginning (m.p. 113 "C). The dinitrile eluted at about 50 methylene chloride and
was obtained as a colorless oil ( 5 g ; 29 mmol of dinitrile; yield 66 %). Crystallization from methanol gave white crystals: m.p. 48-49 "C (lit., 48- 50 "C [19,20], 49-51 "C [12]); infrared spectrum,2240 cm-' (s, C EN).ci

Conversion of 3,3 '-Dithiohispropionitrilr to the Diimidute Dilzydrochloride
To 1.09 g (5.8 mmol) of the dry oil obtained from the alumina column were added 16 ml of dioxane and 0.5 ml of methanol, both dried by reflux with CaHzand then distilled. Gaseous HCI was passed through concentrated H,S04 and a tube of CaCI,, and bubbled into the mixture under cooling in a water-ice bath until the weight gain was about 1.5 g. White crystals began to precipitate after several hours. After 4 days at 4 "C dry ether (about 20 ml) was added to complete the precipitation of the product, and the crystals were filtered and washed with dry ether under dry N, and stored over KOH and PzOs: m.p. 174 "C (lit., 175-176 "C [19], 174- 176 "C [20]); infrared spectrum,in cm-I : 3000 (m, broad), 1630 (s, C = N). The C N peak at 2240 cm- completely disappeared. The synthesis of dimethyl-3,3'-dithiobispropioni-
midate is outlined in Fig. 1.