Butyl chloride HCl method

In a 250 ml. separatory funnel place 25 g. of anhydrous feri.-butyl alcohol (b.p. 82-83°, m.p. 25°) (1) and 85 ml. of concentrated hydrochloric acid (2) and shake the mixture from time to time during 20 minutes. After each shaking, loosen the stopper to relieve any internal pressure. Allow the mixture to stand for a few minutes until the layers have separated sharply draw off and discard the lower acid layer. Wash the halide with 20 ml. of 5 per cent, sodium bicarbonate solution and then with 20 ml. of water. Dry the preparation with 5 g. of anhydrous calcium chloride or anhydrous calcium, sulphate. Decant the dried liquid through a funnel supporting a fluted Alter paper or a small plug of cotton wool into a 100 ml. distilling flask, add 2-3 chips of porous porcelain, and distil. Collect the fraction boiling at 49-51°. The yield of feri.-butyl chloride is 28 g. 

Allyl Chloride. Comparatively poor yields are obtained by the zinc chloride - hydrochloric acid method, but the following procedure, which employs cuprous chloride as a catalyst, gives a yield of over 90 per cent. Place 100 ml. of allyl alcohol (Section 111,140), 150 ml. of concentrated hydrochloric acid and 2 g. of freshly prepared cuprous chloride (Section II,50,i one tenth scale) in a 750 ml. round-bottomed flask equipped with a reflux condenser. Cool the flask in ice and add 50 ml. of concen trated sulphuric acid dropwise through the condenser with frequent shaking of the flask. A little hydrogen chloride may be evolved towards the end of the reaction. Allow the turbid liquid to stand for 30 minutes in order to complete the separation of the allyl chloride. Remove the upper layer, wash it with twice its volume of water, and dry over anhydrous calcium chloride. Distil the allyl chloride passes over at 46-47°. 

Mix 40 g. (51 ml.) of isopropyl alcohol with 460 g. (310 ml.) of constant boiling point hydrobromic acid in a 500 ml. distilling flask, attach a double surface (or long Liebig) condenser and distil slowly (1-2 drops per second) until about half of the liquid has passed over. Separate the lower alkyl bromide layer (70 g.), and redistil the aqueous layer when a further 7 g. of the crude bromide will be obtained (1). Shake the crude bromide in a separatory funnel successively with an equal volume of concentrated hydrochloric acid (2), water, 5 per cent, sodium bicarbonate solution, and water, and dry with anhydrous calcium chloride. Distil from a 100 ml. flask the isopropyl bromide passes over constantly at 59°. The yield is 66 g. 

Owing to the comparatively negligible difference in the cost of bromine and the equivalent quantity of constat boiling point hydrobromio acid, there is little to be gained—apart from the instructional value—in preparing the hydrobromio acid from bromine in the preparation of alkyl bromides. 

CAUTION. Bromine must be handled with great care and in the fume cupboard. The liquid produces painful bums and the vapour is unpleasant. Bromine bums should be treated immediately with a liberal quantity of glycerine. If the vapour is inhaled, relief may be obtained by soaking a handkerchief in alcohol and holding it near the nose. 

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The chemistry of this reaction has been extensively studied by Use and Edman. Although the reaction velocity is different for various amino acids, the reaction is complete in 1 N HCl at 80 °C within 10 min, with virtually all amino acids. This treatment, however, would cause partial hydrolysis of the remaining peptide. The method was made amenable to automation when Edman suggested to separate the thiazolinone derivative from the remaining peptide by extraction of the liberated thiazolinone derivative into butyl chloride and to perform the conversion into the PTH-amino acid outside the reaction vessel. 

The residue of methyl esters (e.g. from esterification according to procedure 2.1.1 above) is treated with 200 pi of methylene chloride, which is evaporated off to entrain any traces of water. Transesterification is with 100 pi of 1.25 M HCl in isobutyl alcohol at 110 °C for 150 minutes [143]. An essentially similar procedure for making isoamyl esters has also been described [144]. The similar method of transbutylation developed by the Missouri group [145] has been replaced by the direct butyl esterification procedure [146, 147]. 

DL-Isoleucine is synthesized in about 56% over-all yield by the method of Hamlin and Hartung (366). o-Oximino- -methyl-w-valeric acid (A) is prepared in 70% yield from ethyl sec.-bulyl acetoacetate, butyl nitrite and sulfuric acid. DL-Isoleucine is prepared in 80% yield by the reduction of (A) with hydrogen, palladium chloride and ethanol. This method is essentially the same as that originated by Bouveault and Locquin (117, 118, 525). By the comparable procedure of Feofilaktov (264, 265) the phenylhydrazone of methyl ethyl pyruvic acid, prepared from sec.-butyl acetoacetate and phenyldiazonium chloride (aniline and NaN02) in 68% yield, is reduced by means of rinc and alcoholic HCl to nearly the theoretical yield of a mixture of DL-isoleucine and DL-allo-isoleucine. Ehrlich (235) synthesized a mixture of isoleucine and allo-isoleucine from 2-methyl-n-butyraldehyde by the Strecker reaction. 

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