1,2 Ethanedithiol

Caution This preparation requires the use of a good hood. 

In a 5-1. round-bottomed flask fitted with an efficient reflux condenser are placed 2750 ml. of 95% ethanol and 609 g. (8.0 moles) of thiourea. The mixture is brought to the reflux temperature on a steam bath, and the refluxing solution is almost clear. The steam is turned off, and 751.5 g. (4.0 moles) of ethylene di-bromide is added in one portion. Within 5 minutes a vigorous 

Concentration of the filtrate to a volume of about 250 ml. and recrystallization from 95% ethanol of the crude isothiuronium salt which separates gives an additional 130 g. of material. The total yield of the salt is 1234 g. (90%). 

A mixture of 255 g. (0.75 mole) of ethylene diisothiuronium bromide and 640 g. (11.4 moles) of potassium hydroxide in 1360 

The reaction may be so vigorous that external cooling is required. A cloth wet with ice water and applied to the flask is sufficient to control the reaction. 

Solubility slightly sol water miscible with many organic solvents. 

Handling, Storage, and Precautions stench Inhalation can cause chest pain, headache, nausea, pulmonary edema LD50 (oral, mouse) 342 mg kg see 1,3-Propanedithiol. Use in a fume hood. 

3-Dithiolane Formation. 1,2-Ethanedithiol (1) condenses with aldehydes, ketones, and acetals to afford 1,3-dithiolanes, - useful for carbonyl protection (eqs 1 and 2). Stability, condensation selectivity, and conditions for carbonyl regeneration parallel those discussed for 1,3-Propanedithiol. Esters and lactones can be protected as ketene dithioacetals and/or dithioortholactones, resistant to nucleophilic attack, using the bis(dimethylalanyl) derivative of (1).  

Ether Cleavage. An acetonide can be cleaved in the presence of a nearby f-butyldiphenylsilyl ether with (1). Under more vigorous conditions, aliphatic methyl ethers are cleaved (eq 3).  

Reduction. Raney Nickel desulfurization of 1,3-dithiolanes effects overall reduction of C=0 to CH2, as does Sodium-Ammonia in THF (eqs 4 and 5). Na/hydrazine is an alternative reagent (eq 6). Peptidic sulfoxides are reduced to thioethers with (1) and an electrophilic catalyst.  

---

This type of chemistry also functions for hydroxyketones and aldehydes. The process using 1,2-ethanedithiol or 2-mercaptoethanol results in cycHc stmctures (eq. 25). The 1,3-ditholenes (X = S) and 1,3-thioxalanes (X = O) resulting from these reactions have been shown to be of interest commercially. 

Thiols iateract readily with many mbber-containing materials. For this reason, care should be taken ia the selection of gasket and hose materials. Teflon, Kel-F, Viton, or other suitable fluoroelastomers function as gasket materials. Viton is suitable for hoses. Carbon steel is useful for many thiols, although some thiols become very discolored when carbon steel is utilized. In these cases, the use of stainless steel is very desirable. Isolation from air and water also minimizes color formation. 2-Mercaptoethanol and 1,2-ethanedithiol should be stored ia stainless steel (61). 

At about the same time Pedersen s work was underway, Bradshaw and his coworkers had undertaken the systematic preparation of numerous mono- and polysulfur macrocycles The syntheses were carried out in a fashion similar to that shown in Eq. (6.3). The two principal sources of sulfur in the first paper from this groupwere sodium sulfide and 1,2-ethanedithiol. The latter was utilized in the presence of sodium hydroxide base. Ethanol was generally used as solvent and the reactions were conducted at high dilution. Products were purified either by vacuum distillation or recrystallization as appropriate. The yields were generally in the 5—30% range. 

Similar cyclization of 367 leading to low yields (20%) of benzodithiine 368 was observed with triethylamine in DMSO (Eq. 32) (76ZOR844). On the other hand, coumarin derivative 369 treated with 1,2-ethanedithiole in the presence of triethylamine provided relatively stable spiro compound 370 (Eq. 33) (89ZOR669). 

The DBSA-system is also applicable for the dithioacetalization of aldehdyes and ketones with 1,2-ethanedithiol to give the corresponding dithioacetals (Scheme 5.4, d). Increasing the reaction temperature decreases the yield of the products. Interestingly, increases in the concentration of the surfactant also decrease the yield of products formed, while shortening the alkyl chain of the surfactant abolishes its catalytic activity. Optical microscopy shows the formation of micelles, which are proposed to form hydrophobic environments and decrease the effective concentration of water and facilitate the dehydrative condensation reactions. 

Tetrathia[6.6.1]propellane 72 has been prepared 21. This is the parent of the dibenzo compound 7/just mentioned 20). The same tetrasubstituted cyclopropane 24 was used, this time simply with 1,2-ethanedithiol, under conditions of high dilution... 

Despite the latent reactivity of ketene thioacetals,3-4 some members of this class such as the title compound have been little studied, perhaps because of preparative inaccessibility. The only previously reported route to 2-methylene-1,3-dlthiolane involves monoacetylation of 1,2-ethanedithiol, cyclization to 2-methyl-1,3-dithiolan-2-yl perchlorate, and exposure of this salt to diisopropylethylamine in acetonitrile 5... 

Ethanedithiol was purchased from the Aldrich Chemical Company, Inc., and used without further purification. 

Aldehydes and ketones have been protected as acetals and dioxolanes using orthoformates, 1,2-ethanedithiol or 2,2-dimethyl-l,3-dioxolane by Hamelin and coworkers. This acid-catalyzed reaction proceeds in the presence of p-toluenesulfonic acid (p-TsOH) or KSF clay under solvent-free conditions (Scheme 6.2). The yields ob-... 

Ethane, 1-chloro-l-nitro-, 37, 25 1,2-Ethanedithiol, 30, 35 Ethanol, 2,2-dichloro-, 32, 46 Ethanolysis, 33, 25 Ether, benzhydryl 2-chloroethyl,... 

The resin product was suspended in TFA (9 mL), into which was immediately added water (0.45 mL), 1,2-ethanedithiol (0.45 mL), and triisopropylsilane (0.1 mL). The mixture was left, with occasional agitation, at 30°C for 4h. The suspension was then filtered, the spent resin washed with TFA (3x1 mL) and the combined filtrate was evaporated to dryness in vacuo. The residual material was then triturated with diethyl ether (10 mL) to give a white solid, which was filtered, washed with diethyl ether (3 x 10 mL), and dried in vacuo to afford the title compound... 

Caution This preparation should be conducted in an efficient hood because of the obnoxious odor of 1,2-ethanedithiol. 

---