M-Butyl bromide

Sodium cyanide does not dissolve m butyl bromide The two reactants contact each other only at the surface of the solid sodium cyanide and the rate of reaction under these con ditions IS too slow to be of synthetic value Dissolving the sodium cyanide m water is of little help because butyl bromide is not soluble m water and reaction can occur only at the interface between the two phases Adding a small amount of benzyltrimethyl ammonium chlonde however causes pentanemtnle to form rapidly even at room temper ature The quaternary ammonium salt is acting as a catalyst it increases the reaction rate How7... 

In a 5-I. round-bottom flask, fitted with a stirrer, separatory funnel and a reflux condenser to the upper end of which a calcium chloride tube is attached, is placed 150 g. of magnesium turnings. A small crystal of iodine (Note i) and about 100 cc, of a mixture of 822 g. (6 moles) of M-butyl bromide and 2 1. of anhydrous ethyl ether are added. As soon as the reaction starts, 350 cc. of anhydrous ether is added and the remainder of the -butyl bromide solution is dropped in at such a rate that the mixture boils continuously. The time of addition (one and one-half hours) may be decreased by cooling the flask externally. Stirring is started as soon as enough liquid is present in the flask. 

If the intermediate reacts with Y (which may be the solvent) to give product much faster than it does with X to revert to reactant, then Eq. (8-65) will tend to the simple first-order form, v = A i[R-X]. In aqueous solvents /m-butyl bromide exhibits this kinetic behavior. 

The method described is successfully used for the alkylation and aralkylation of ethyl and /-butyl phenylacetate.3 The alkylation of ethyl phenylacetate with methyl iodide, M-butyl bromide, benzyl chloride, and a-phenylethyl chloride affords the corresponding pure monoalkylation products in 69%, 91%, 85%, and 70% (erythro isomer) yields, respectively. The alkylation of /-butyl phenylacetate with methyl iodide, M-butyl bromide, a-phenylethyl chloride, and /3-phenylethyl bromide gives the corresponding pure monoalkylated products in 83%, 86%, 72-73%, and 76% yields, respectively. 

Certain of the monoalkylated ethyl phenylacetates have been further alkylated with alkyl and aralkyl halides to produce the corresponding disuhstituted phenylacetic esters.4 Ethyl 2-phenyl-propanoate has been alkylated by methyl iodide to give pure ethyl 2-methyl-2-pheny]propanoate in 81% yield. Similarly, the alkylations of ethyl 2-phenylhexanoate with methyl iodide, M-butyl bromide, and benzyl chloride gave the corresponding pure dialkylated products in 73%, 92%, and 72% yields, respectively. 

Butylation of ethyl phenylacetate, /-butyl phenylacetate, and ethyl 2-phenylhexanoate has also been accomplished with M-butyl bromide and sodium hydride in refluxing monoglyme in 64%, 66%, and 56% yields, respectively.6 In contrast to the sodium amide reactions above, however, careful fractionation of the crude products was required to obtain pure products. 

Freshly distilled diphenylmethane and M-butyl bromide were used. 

A mixture of 28 g. (0.2 mole) of o-nitrophenol (Note 1), 30 g. (0.22 mole) of M-butyl bromide, 28 g. (0.2 mole) of anhydrous potassium carbonate, and 200 ml. of dry acetone in a 1-1. round-bottomed flask is refluxed on a steam bath for 48 hours (Note 2). At the end of this time the acetone is distilled from the mixture, 200 ml. of water is added to the residue, and the product is extracted with two 100-ml. portions of benzene. The combined benzene extracts are washed with three 100-ml. portions of 10% sodium hydroxide, the benzene is removed by distillation at... 

A technical grade of o-nitrophenol was used the yield is no better with the pure material. In place of M-butyl bromide, a corresponding amount (36.8 g.) of the iodide can be used with no change in yield. 

In the flask is placed 2.5 1. of absolute alcohol (Note 2), and then there is added gradually 115 g. (5 moles) of metallic sodium cut into pieces. This requires three to four hours. After all the sodium has dissolved, 650 g. (5 moles) of ethyl acetoacetate (Note 3) is added. The stirrer is started and the solution heated to gentle boiling. To the boiling solution 750 g. (5.47 moles) of M-butyl bromide (Note 4) is added over a period of about two hours. The refluxing and stirring are continued until a sample of the solution is neutral to moist litmus paper. The time varies from six to ten hours. 

The M-butyl bromide (Org. Syn. 1, 5) boiled over a range of three degrees. The excess was used in order to decrease the time necessary to complete the reaction. 

By the same general method, M-butyl bromide gives m-valeric acid in 64-65 per cent yield, bromobenzene gives benzoic acid in 70-71 per cent yield, and cyclohexyl bromide gives hexahydrobenzoic acid in 68 per cent yield. 

Eastman Organic Chemicals Eastman grade M-butyl bromide was distilled b.p. 101-102°. 

M-Caproic acid may be prepared by this method from M-butyl bromide in similar yields (see also Org. Syn. 11, 78). In this case a partial decomposition of the substituted malonic acid is brought about by refluxing the aqueous solution in the 12-1. flask after the addition of the hydrochloric acid. Butylma-lonic acid is appreciably soluble in water, and separation of the oUy layer does not occur until it has been largely decomposed to caproic acid. The time required is about eight to ten hours. It is advisable to heat the acid layer under air reflux as in the case of pelargonic acid. 

Aqueous sodium bicarbonate was used to wash the crude M-butyl bromide. 

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