Chloroform formation processes

Although 4-hydroxybenzaldehyde can be made by the saligenin route, it has been made historically by the Reimer-Tiemann process, which also produces sahcylaldehyde (64). Treatment of phenol with chloroform and aqueous sodium hydroxide results in the formation of benzal chlorides, which are rapidly hydrolyzed by the alkaline medium into aldehydes. Acidification of the phenoxides results in the formation of the final products, sahcylaldehyde and 4-hydroxybenzaldehyde. The ratio of ortho and para isomers is flexible and can be controlled within certain limits. The overall reaction scheme is shown in Figure 1. Product separation is accomphshed by distillation, but this process leads to environmental problems because of the quantities of sodium chloride produced. 

The common impurities found in amines are nitro compounds (if prepared by reduction), the corresponding halides (if prepared from them) and the corresponding carbamate salts. Amines are dissolved in aqueous acid, the pH of the solution being at least three units below the pKg value of the base to ensure almost complete formation of the cation. They are extracted with diethyl ether to remove neutral impurities and to decompose the carbamate salts. The solution is then made strongly alkaline and the amines that separate are extracted into a suitable solvent (ether or toluene) or steam distilled. The latter process removes coloured impurities. Note that chloroform cannot be used as a solvent for primary amines because, in the presence of alkali, poisonous carbylamines (isocyanides) are formed. However, chloroform is a useful solvent for the extraction of heterocyclic bases. In this case it has the added advantage that while the extract is being freed from the chloroform most of the moisture is removed with the solvent. 

Pyrrolealdehyde has been prepared from pyrrole, chloroform, and potassium hydroxide from pyrrolemagnesium iodide and ethyl, propyl, or isoamyl formate and, by the method here described, from pyrrole, phosphorus oxychloride, and dimethylformamide. Smith has suggested a possible intermediate in this process. The method has also been applied to substituted pyrroles and is similar to that described in this series for the preparation of -dimethylaminobenzaldehyde from di-methylaniline. ... 

The actual formylation process is preceded by the formation of dichlorocarbene 3 as the reactive species. In strongly alkaline solution, the chloroform is deproto-nated the resulting trichloromethide anion decomposes into dichlorocarbene and a chloride anion ... 

One application in liquid chromatography which does alter the separation process is the use of a specific series of derivatives to enable the separation of chiral (optical isomers) forms of alcohols, amines and amino acids using reverse-phase separation. FLEC is available in the two chiral forms (+)-l-(9-fluorenyl) ethyl chloroformate and (—)-l-(9-fluorenyl) ethyl chlorofor-mate (Figure 3.12). Reaction of two stereoisomers of a test compound (e.g. T+ and T—) with a single isomer of the derivatizing reagent (e.g. R+) will result in the formation of two types of product, T+R+ and T—R+. It is possible to separate these two compounds by reverse-phase chromatography. 

The generation of the dichloromethane under phase-transfer conditions may be facilitated by the addition of a trace of ethanol. Alkoxide anions, generated under the basic conditions, are more readily transferred across the two-phase interface than are hydroxide ions (see Chapter 1). Although this process may result in the increased solvolysis of the chloroform, it also produces a higher concentration of the carbene in the organic phase and thereby increases the rate of formation of the cyclopropane derivatives from reactive alkenes. 

Fluoro- and chlorogermenes 24a and 24b are evidenced by a trapping reaction with the transient formation of 59, which loses dichlorocarbene to give 6032 [Eq. (15)]. A similar reaction process with addition of the CH bond of chloroform to the Ge = N double bond of a germanimine Ge = N followed by loss of CC12 has also been reported.59... 

The chemistry of the isocyanides began when, in 1859 Lieke formed allyl isocyanide from allyl iodide and silver cyanide, and when, in 1866 Meyer ° produced in the same way 1-isocyano-l-desoxy-glucose. In 1867, Gautier used this procedure to prepare alkylisocyanides, and Hofmann introduced the formation of isocyanides from primary amines, chloroform, and potassium hydro-xyde. Gautier also tried to prepare an isocyanide by dehydrating an amine formiate via its formylamine using phosphorus pentoxide, but this process produced no isocyanide. Gautier had not yet realized that acidic media destroyed the isocyanides. 

As the solubility of this peptide in water is very low, the peptide can be associated with the liposomal membrane. As the peptide is only sparingly soluble in methanol or chloroform, DMSO had to be used as dissolution medium for mixing the peptide with the lipids for liposome formation. A lOmg/mL stock solution in DMSO of the peptide could be obtained. Appropriate amounts of lipid stock solutions and the peptide stock solution were mixed (lipid peptide ratio = 95 5) and processed as thoroughly described in the... 

There was no evidence of a second-order term in amine, nor did amine self-association account for the non-linear behaviour. Hammett p values (for variation of RNHSO2) determined for formation of the complex [S.amine] (p = 1.64) and for expulsion of the anion ( ONp) (pacyi = -1-78) are consistent with an E cB process and uncomplicated by any steric effects of bound amine in the complex. The value of Pacyi is identical with that reported previously for ElcB reaction of the same esters in 50% acetonitrile-water and much greater than for their 2-type reactions in chloroform. Consequently, an ElcB mechanism involving extensive S-O bond cleavage with the formation of a A(-sulfonylamine, ArN=S02, is supported. 

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