Alkyl bromides, general method

The trimethylene chlorobromide used boiled at 142-1470. It may be prepared in 75-85 per cent yields from trimethylene chlorohydrin (p. 112) by the general method for the preparation of alkyl bromides described in Org. Syn. 1,1. 

Ficini and Barbara [14, 15] prepared lithium aminoacetylides and allowed them to react with alkyl bromides or tosylates in hexamethylphosphoramide to give good yields of substituted ynamines (Eq. 16). This method shows promise of being a general route to ynamine derivatives. 

This procedure3 is an example of a simple and general method for preparation of primary and secondary dialkyl and alkyl aryl thioethcrs via alkylation of sodium sulfide or sodium alkyl- or arylthiolates with alkyl chlorides or bromides. The method is an... 

Transalkylation Reaction. The alkylation reaction of potassium ferrocyanide with alkyl bromides activated at the a-carbon by a double bond (14) gave in each case good conversions to the corresponding isonitrile complexes. Since this method is limited to alkyl halides activated at the Qj-carbon by a double bond, it was of interest to develop a general method for the preparation of aliphatic isonitrile complexes. 

The use of a modified sodium bromide-sulfuric acid method for the preparation of alkyl bromides is described in connection with the preparation of ra-butyl bromide. This method has been used also for the preparations of iso-amyl and trimethylene bromides, but, in general, the yields were found to be somewhat lower than those obtained with the hydrobromic-sulfuric acid method. 

Normally, the most practical vinyl substitutions are achieved by use of the oxidative additions of organic bromides, iodides, diazonium salts or triflates to palladium(0)-phosphine complexes in situ. The organic halide, diazonium salt or triflate, an alkene, a base to neutralize the acid formed and a catalytic amount of a palladium(II) salt, usually in conjunction with a triarylphosphine, are the usual reactants at about 25-100 C. This method is useful for reactions of aryl, heterocyclic and vinyl derviatives. Acid chlorides also react, usually yielding decarbonylated products, although there are a few exceptions. Likewise, arylsulfonyl chlorides lose sulfur dioxide and form arylated alkenes. Aryl chlorides have been reacted successfully in a few instances but only with the most reactive alkenes and usually under more vigorous conditions. Benzyl iodide, bromide and chloride will benzylate alkenes but other alkyl halides generally do not alkylate alkenes by this procedure. 

Alkyl iodides are the most easily formed of the alkyl halides and the slow distillation of the alcohol with constant boiling hydriodic acid is a general method of preparation (e.g. Expt 5.57). As with the corresponding chlorides and bromides (q.v.), the yields of the required alkyl iodides in this reaction may be diminished in the case of certain (tertiary and secondary) alcohols as a result of skeletal rearrangement. 

One generally applicable method of oxidation for alkyl bromides involves the Pummerer rearrangement. This gives aldehydes upon rearrangement of the alkyl aryl sulfoxide formed by displacement of halide by thiolate followed by oxidation (equation 41)358. 

N-Ethyl-/>-chloroaniline has been prepared by alkylation of / -chloroaniline with ethyl bromide 4 5 and by reduction of aceto-/-chloroanilide with lithium aluminum hydride.6 The present procedure, which is based on the results of an investigation by Roberts and Vogt,3 is a convenient general method for preparation of pure N-alkyl aromatic amines. 

A general method for the preparation of primary alkyl bromides of the type RCH,CH,Br consists in the treatment of the alcohol with excess aqueous hydrobromic acid together with sulfuric acid (90-95%). The hydrobromic acid is readily prepared from bromine and sulfur dioxide. 

The alkylation of nitriles has been developed as a general method for the preparation of substituted acetonitriles. An excellent discussion of the literature to 1937 has been given. The procedure consists in treating a nitrile in an inert solvent with finely divided sodium amide and the halogenated compound, followed by careful hydrolysis with water. Common solvents are ether, benzene, toluene, or liquid ammonia. Mono-, di-, and tri-alkylated products are possible, as shown by the alkylation of acetonitrile with ethyl bromide however, the mixtures can often be separated by fractional distillation. 

The reaction of ammonia with primary alkyl halides generally forms a mixture of primary, secondary, and tertiary amines and even a certain amount of the quaternary ammonium halide. Still, the method may be profitable for obtaining primary amines if the halogen compound is above C, and excess ammonia is employed, for then polyalkylation is less likely and the products, having widely different boiling points, are more readily separated. Thus w-butyl bromide and a large excess of ammonia in alcohol solution at room temperature give a 47% yield of w-butylamine. ... 

Table XIII. of the Appendix gives a list of compounds prepared by the following general method, together with their physical constants, Three times the ealeulated quantity of magnesium alkyl halide is used, and after the introduction of the tin alkyl halides the mixture is boiled under reilux for two hours, the etlier removed, and the residue baked on the water-buth lor one liour. After cooling, ether is added, and the whole deosed with water. Mixed tin tetra-alkyls are converted into inixed tin trialkyl bromides of the type R R SnX by the action of bromine at - 40° to —30° C., ati alkyl group being split out, this resembling the bromination of lead alkyls.

The most general method of preparing allyl ethers is to react the alcohol with allyl bromide or iodide in the presence of sodium hydride. The reaction is best carried out in a polar solvent, usually DMF [72]. Alcohols may also be alkylated after conversion to their barium salts. This technique is employed in the case of A-acyl derivatives of aminosugars to avoid any risk of alkylation at nitrogen which would accompany the use of sodium hydride as the base [73,74]. Conversion of alcohols to allyl carbonates, followed by palladium-catalyzed extrusion of CO2, constitutes a milder alternative to the classical Williamson-type pro-... 

A general method fen the synthesis of alkyl iodides is the reaction of tosylates or methanesulfonates with sodium iodide in acetone or magnesium iodide in diethyl ether (equation 30). The reaction is not always a clean Sn2 process. Stereoselectively deuterated neopentyl tosylate, for example, gives with Nal in HMPA only low yields (34%) of the racemic iodide (equation 31). This is in contrast to analogous reactions with bromide and chloride (see Sections 1.7.3.2 and 1.7.2.2), where better yields with complete inversion are observed. 

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