Chloroform, reaction with base

Heterocyclic Alcohols. Thek reactions with chloroformates lead to carbonates. Thus furan- and tetrahydrofuran-derived alcohols give the corresponding carbonates in 75% yield (15). Inorganic bases and tertiary amines as acid acceptors increase the rate and yield in this reaction. 

Amino Alcohols. Reaction of chloroformate is much more rapid at the amino group than at the hydroxyl group (4—8). Thus the hydroxy carbamates, which can be cyclized with base to yield 2-oxazoHdones, can be selectively prepared (29). Nonionic detergents may be prepared from poly[(ethylene glycol) bis(chloroformates)] and long-chain tertiary amino alcohols (30). 

The Ciamician-Dennstedt reaction involves the reaction of a pyrrole (1) with the carbene generated from chloroform and a base to provide a 3-chloropyridine (2, Scheme 8.3.1). 

The idea that dichlorocarbene is an intermediate in the basic hydrolysis of chloroform is now one hundred years old. It was first suggested by Geuther in 1862 to explain the formation of carbon monoxide, in addition to formate ions, in the reaction of chloroform (and similarly, bromoform) with alkali. At the end of the last century Nef interpreted several well-known reactions involving chloroform and a base in terms of the intermediate formation of dichlorocarbene. These reactions included the ring expansion of pyrroles to pyridines and of indoles to quinolines, as well as the Hofmann carbylamine test for primary amines and the Reimer-Tiemann formylation of phenols. 

Despite several attractive features in this method of direct halogen introduction and the obvious applications in the synthesis of deoxy sugars, its uses have not been further exploited by other groups of workers. Some new related methods have become available which reportedly eliminate the difficulties previously encountered such as rearrangement, unreactivity due to steric hindrance, and phosphonate ester formation. The reaction is based on the observation (28) that triethylphosphine reacts with ethanol and carbon tetrachloride to give ethyl chloride, chloroform, and triethylphosphite. In a new adaptation (76, 77) of this... 

An early method developed for the assay of detergents based upon the sodium salts of the higher homologues of the alkanesulphonic acids,21 involved treatment of an aqueous solution of the detergent with methylene blue in the presence of chloroform. Reaction takes place between the ionic dyestuff (which is a chloride) and the detergent ... 

Chloroform is more rapidly hydrolyzed with base than dichloromethane or carbon tetrachloride and gives not only formic acid but also carbon monoxide Hine has shown that the mechanism of chloroform hydrolysis is quite different from that of dichloromethane or carbon tetrachloride, though superficially the three reactions appear similar. The first step is the loss of a proton to give CCla , which then loses Cl to give dichlorocarbene CCI2, which is hydrolyzed to formic acid or carbon monoxide. 

A tetracarboxylated derivative was prepared recently by reaction of a commercial reactive dye with two molar equivalents of aspartic acid. This novel derivative was evaluated by pad-dry-bake and pad-batch-bake methods under slightly acidic conditions in the presence of cyanamide as activator [49]. An interesting disperse dye containing a novel reactive anhydride system (7.54) was prepared from the parent dye carboxylate (7.53) by reaction with ethyl chloroformate in the presence of a tertiary base (Scheme 7.32). Such dyes will... 

The hydrochloric acid is removed by the strong tertiary base, methyldibutylamine, which has a soluble hydrochloride. In B.P. s 631,549 and 652,981 it was shown that compound (II) could be prepared by the action of dimethylamine on P0C13 in chloroform containing an excess of methylbutylamine. The further reaction with water is very conveniently carried out in the same system by adding an excess of aqueous sodium hydroxide solution. The chloroform layer contains the tertiary amine and (I). The solvent and amine are stripped off leaving the product. Side reactions take place, and the commercial product also contains some triphosphoric pentadimethylamide (I A) and smaller amounts of other phosphoric amides. The compound (I A) is itself also a valuable systemic insecticide. 

FIGURE 3.15 Protection of amino groups as urethanes by reaction with succinimido carbonates (path A).33-36 The mixed carbonate is a weaker electrophile than the chloroformate. The V-alkoxycarbonylamino-acid anion does not react with the reagent (path B) in the presence of the weak base hence no dimer is formed. R = triethyl or dicyclohexyl. 

Compared with the classical procedures, which employ chloroform and dry potassium /ert-butoxide, Makosza s method is several magnitudes superior, in spite of the normally recognized requirements that the dichlorocarbene should be produced under totally anhydrous conditions. Several early reports of the reactions of dichlorocarbene, generated by Makosza s procedure, led to suggestions that the activity of the carbene was considerably greater than that of the classically produced carbenes. This assumption was based on the overall higher yields of dichlorocyclopropanes derived from the reaction with alkenes, and upon the observation that weakly activated alkenes reacted with Makosza carbenes, but not with the classically produced carbenes. A consideration of the mechanism of formation of the carbenes under phase-transfer catalytic conditions exposes the fallacies in the assumptions. 

One useful reaction utilizing alkyl chloroformate is the reaction with an amine in base to form a carbamate (urethane). Figure 12-41 illustrates this reaction. 

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