Hypnotics and Anticonvulsants. Iii. Carbamates of Tertiary Acetylenic Carbinols

O-Carbamates

“…Similar results were obtained with potassium cyanate [22,23]. Tertiary alco hols were reported earlier to react with potassium cyanate in acetic acid to give dehydration or rearrangement but no carbamate [24]. Marshall [25] and others [26,27] described a method whereby tertiary alcohols reacting in situ generated cyanic acid from a mixture of anhydrous sodium cyanate in trichloroacetic acid.…”

“…Although earlier investigators [24,29,30] reported that cyanic acid reacts with alcohols to give allophonates, Loev [28] never detected any of these in his procedure. The only by-product was trifluoroacetamide, which did not present a difficulty because of its high solubility in water and organic solvents.…”

“…(2) Preparation of tertiary alkyl esters of carbamic acid by the ammono lysis of mixed phenyl alkyl carbonates to yield alkyl carbamate and phenol [24,40,41].…”

Synthesis of a Steroidal Dicarbamate Related to Meprobamate from 3‐Ketobisnorcholenal

“…To avoid undesirable side reactions involving the 3-keto groups it was necessary to protect it during the course of the reactions. Reaction of 7 with phenyl chlorocarbonate in pyridine led to the formation of the mixed bis carbonate (8)," which could be ammonolyzed either in liquid ammonia or in ethanolic ammonia solution to provide dicarbamate (9). Towards this end, ketoaldehyde (1) was condensed with malononitrile in aqueous dioxane in the presence of {3-alanine at room temperature to give dicyanoketone (3): Ketalization of 3 with ethylene glycol gave dicyanomethylene dioxolan derivative (4), which was converted to an epimeric mixture of the derived protected aldehyde 5 by base catalyzed hydrolysis!…”

“…After cooling and filtering, the precipitate was recrystallized from methanol to give 1.76 g of the product 3 -Dicyanomethylene -23, 23 -dicyano -A'.2' -norcholadiene (2). The crude mixed dicarbonate (8) 3-0xo-20,20-bishydroxymethylpregn-4-ene dicarbonate (11). A solution of 2.33 mg l3-alanine in 0.5 ml of water was added dropwise to the mixture.…”