Phosgene aryl chloroformates

A general method of synthesis of the aryl chloroformates involves the reaction of phosgene with phenoxide, M[OAr], dissolved in a suitable solvent at low temperatures [1442] ... 

Phosgene reacts readily with aliphatic alcohols at room temperature or below to afford the corresponding aliphatic chloroformates in good yields, but phenols are much less reactive toward phosgene. Elevated temperatures (>100 °C) and scavengers or specifically designed catalysts (N,N -dimethylpropyleneurea, 2-undecylpyridine) are required to prepare aryl chloroformates [8, 9]. 

Acid chlorides are used for the quantitative deterrnination of hydroxyl groups and for acylation of sugars. Industrial appHcations include the formation of the alkyl or aryl carbonates from phosgene (see Carbonic and chloroformic esters) and phosphate esters such as triethyl, triphenyl, tricresyl, and tritolyl phosphates from phosphoms oxychloride. 

Alcohols and phenols can be attached to support-bound alcohol linkers as carbonates [467,665,666], although few examples of this have been reported. For the preparation of carbonates, the support-bound alcohol needs to be converted into a reactive carbonic acid derivative by reaction with phosgene or a synthetic equivalent thereof, e.g. disuccinimidyl carbonate [665], carbonyl diimidazole [157], or 4-nitrophenyl chloro-formate [467] (see Section 14.7). The best results are usually obtained with support-bound chloroformates. The resulting intermediate is then treated with an alcohol and a base (DIPEA, DMAP, or DBU), which furnishes the unsymmetrical carbonate. Carbonates are generally more resistant towards nucleophilic cleavage than esters, but are less stable than carbamates. Aryl carbonates are easily cleaved by nucleophiles and are therefore of limited utility as linkers for phenols. 

Carbamates have mainly been used in solid-phase synthesis as linkers and protective groups for amines (see Sections 3.6.2 and 10.1.10.1). Carbamates are generally prepared by treating amines with aryl carbonates or chloroformates, which can be prepared from alcohols and phosgene or synthetic equivalents thereof. The alternative route, in which carbamates, isocyanates, or carbamoyl chlorides are reacted with alcohols, is less widely used, but can also lead to satisfactory results on insoluble supports (Tables 14.7 and 14.8). 

Dithiocarbamic salts are suitable starting materials for the preparation of isothiocyanic esters (mustard oils), their reactions with heavy-metal salts,771 chloroformic esters,772 phosgene,768 carbodiimides,805 phosphorus oxychloride,806 aryl cyanates,732 or sodium hypochlorite807 usually giving good yields. Reaction of amines 808,809 or their hydrochlorides with thiophosgene810 is also generally applicable. 

Over eighty N-aryl oxadlazolones were synthesized by a procedure described by Boesch in a German patent (15). This consists of reacting aryl hydrazines with a chloroformic ester followed by ring closure with phosgene. Representative structures are listed in Table 2. 

Thus, the chloroformates of primary and secondary alcohols, prepared by reaction of the alcohol with phosgene, are reduced to the corresponding alkane in excellent yield on reaction with tri-n-propylsilane in the presence of t-butyl peroxide at 140 °C yields are low for aryl and benzyl alcohols. A method for the direct replacement of the hydroxy-group of alcohols by alkyl or aryl groups has been described (see Scheme 11, ref. 67). 

The preparation of chloroformates of aryl ketones bearing aromatic hydroxyl functions using the phosgene equivalents diphosgene and triphosgene has been claimed in patent literature [62]. 

Except at very low oxygen pressures, the first step [equation (5.185)] is, as usual, rate determining. The reaction is accelerated by E and — / substituents (e.g., aryl, methyl) but especially strongly by — substituents, in particular alkoxyl. Ethers therefore autooxidize very easily indeed, giving hydroperoxides, which are often dangerously explosive. Numerous explosions have occurred through the distillation of ethers from which the peroxides had not first been removed. Another example is chloroform, which autooxidizes rather easily to phosgene. 

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