Reagents Ethyl Chloroformate, Phosgene, or Carbon Disulfide

Reagents Ethyl Chloroformate, Phosgene, or Carbon Disulfide 

The historical origin of this reaction is the use of phosgene on 2-amino-benzylamines to prepare 3,4-dihydroquinazolin-2-ones.58,68 In a more recent example of the use of this reagent, a solution of it in chloroform was stirred with one of traw-l-amino-2-aminomethylcyclohexane in aqueous alkali for 3 days at 20°C, producing an excellent yield of trans-3,4,4a,5,6,7,8,8a-octahydroquinazolin-2-one (the ethyl chloroformate approach was first attempted, but the intermediate urethane could not be cyclized).61 When carbon disulfide replaced the phosgene and alkali, the corresponding 2-thione was produced in excellent yield.61 

The use of carbon disulfide dates from 1895, when Busch condensed 2-aminobenzylamine with this reagent in boiling ethanolic sodium ethoxide to give 3,4-dihydroquinazoline-2-thiones.68 This procedure was also suitable for 2-amino-JV-alkyl- and -arylbenzylamines. When ammonia replaced the stronger base, the intermediate dithiocarbamate (74) was isolated in the absence of base, a salt of 74 with the original diamine was obtained. As is usual with carbon disulfide, the aliphatic rather than the aromatic amino group is preferentially attacked.68 

Another unusual closure led to the production of 8-aminoimidazo-[l,5-a]pyrazine-3-thiol (76) from 2-amino-3-aminomethylpyrazine (see 9) and carbon disulfide in pyridine.59 

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