Chlorosulfonyl isocyanate, in nitrile

Chloropropionitrile, 50, 20 Chlorosulfonyl isocyanate, in nitrile synthesis, SO, 52 precautions, 50,18... 

Synthesis of nitriles (2, 70). Lohaus has published two procedures which illustrate the use of chlorosulfonyl isocyanate for the preparation of nitriles. One, the preparation of 2,4-dimethoxybenzonitrile,8 illustrates the reaction of the reagent with aromatic compounds that readily undergo electrophilic substitution. Thus reaction of resorcinol dimethyl ether (1) with chlorosulfonyl isocyanate in methylene chloride gives the amide N-sulfonyl chloride (2), which on treatment with an amide9 gives 2,4-dimethoxybenzonitrile (3) in 95-96% yield with a purity of 98%. 

Electrophilic reaction of heterocycles, such as thiophene or indole, with equimolar amounts of chlorosulfonyl isocyanate in dry ether or acetonitrile at 0-5 °C produces N-chlorosulfonyl-substituted heterocycles (173), which on treatment with DMF gave nitriles in good yields (equations 90 and 91)83. 

An amide at the 2-position as in 231 was dehydrated to the nitrile 232 using chlorosulfonyl isocyanate and triethylamine (Equation 18) <1982AP545>. 

In a modification of the original method. Read replaced a-ammo acids with o-amino nitriles. Chlorosulfonyl isocyanate is an excellent alternative lo alkaline eyanates in the preparation of hydanloins from sterically hindered or lahile amino nitriles. 

Reaction of Jt-excessive heterocycles (e.g. thiophene, indole), enol ethers (e.g. dihydropyran) and enol acetates, and carboxylic acids with chlorosulfonyl isocyanate leads in generally excellent yields to A-chlorosulfonylamides. These intermediates are converted into the corresponding nitriles by heating in DMF, although the yields can be somewhat variable. A recent reinvestigation of the N-chlorosulfonylamide to nitrile conversion revealed that treatment of the amides with one equivalent of triethylamine led to formation of the nitriles in excellent yield. Clearly, the mechanisms of the DMF and the EtsN induced transformations are different. 

The other procedure10 illustrates a general method for conversion of carboxylic acids into the corresponding nitriles. Treatment of cinnamic acid (4) with chlorosulfonyl isocyanate gives the carboxylic acid amide N-sulfonyl chloride (5). As above, treatment of (5) with DMF gives cinnamonitrile (6) in 78-87% yield. 

Chlorosulfonyl isocyanate, Cl-S02-N=00, is an effective dehydrating agent for the preparation of various aryl- and alkyl-nitriles from the corresponding amides and aldoximes in yields of 74-87% and 75-86%, respectively [1128],... 

General procedure. Nitriles from aldoximes [1128] To a magnetically stirred solution of the aldoxime (10 mmol) and dry triethylamine (20 mmol) in dry dichloro-methane (10 mL), a solution of chlorosulfonyl isocyanate (15 mmol) in dichloro-methane (10 mL) is added at 0 °C. The reaction mixture is stirred for 8 h at room temperature and then poured into water (caution ). The dichloromethane layer is separated and the aqueous layer is extracted with dichloromethane (3 x 25 mL). The organic layers are combined, washed with water, and dried over anhydrous sodium sulfate. Evaporation of the solvent gives the nitriles, which are purified by distillation or recrystallization. 

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