Submitted by J. C. Eck and C. S. Marvel.
Checked by C. R. Noller and William Munich.
1. Procedure
(
A)
dl-ε-Benzoyllysine.—A solution of
180 g. (0.57 mole) of ε-benzoylamino-α-bromocaproic acid (p. 74) in
2 l. of aqueous ammonia (sp. gr. 0.9) is filtered into a
5-l. flask and allowed to stand for two days. Any crystals which have formed at the end of this time are filtered, and the filtrate is evaporated on a
steam bath at reduced pressure to about 1 l. The crystals are filtered, combined with the first crop, and washed with
100 cc. of alcohol and finally with
100 cc. of ether. The aqueous filtrate is evaporated under reduced pressure to dryness; the residue is washed with two 100-cc. portions of water to remove the
ammonium bromide, and then with
50 cc. of alcohol, followed by
50 cc. of ether. The total yield of
ε-benzoyllysine, melting at
265–270°, is
100–116 g. (
70–81 per cent of the theoretical amount).
(
B)
dl-Lysine Dihydrochloride.—A solution of
100 g. (0.4 mole) of benzoyllysine in a mixture of
600 cc. of hydrochloric acid (sp. gr. 1.18) and 400 cc. of water is boiled under a
reflux condenser for ten hours. The mixture is cooled and the
benzoic acid removed by filtration. The filtrate is evaporated on a
water bath under reduced pressure until a thick syrup remains. The syrup is transferred to a
1.5-l. beaker by means of
four volumes (about 400 cc.) of hot absolute alcohol and filtered if necessary. The solution is cooled to 15–20°, and
500 cc. of ether is added slowly with stirring. The precipitate, after filtering and drying, melts at
187–189° and weighs
67–75 g. (
76–85 per cent of the theoretical amount); it is analytically pure
lysine dihydrochloride (Note
1).
(
C)
dl-Lysine Monohydrochloride.—To a solution of
55 g. (0.25 mole) of lysine dihydrochloride in
1 l. of boiling 95 per cent alcohol (Note
2) is added, with stirring, a solution of
25 g. (0.32 mole) of pyridine in
40 cc. of hot 95 per cent alcohol. The white, crystalline monohydrochloride separates immediately. After cooling overnight in a refrigerator the solid is filtered and washed with two
50-cc. portions of cold absolute alcohol. After drying, the product melts at
260–263° and weighs
42–43 g. (
91–94 per cent of the theoretical amount).
For further purification to remove any
pyridine hydrochloride, the above product is dissolved in 85 cc. boiling water, and
650 cc. of boiling 95 per cent alcohol added with stirring. After cooling overnight in the refrigerator the solid is filtered, and washed with one
20-cc. portion of cold absolute alcohol. There is obtained
40–42 g. (
95–97 per cent recovery) of monohydrochloride melting at
263–264° (corr.).
2. Notes
1. If a product of lower melting point is obtained, it may be purified by dissolving in
1 l. of hot 95 per cent alcohol, filtering if necessary, cooling, and, without removing any material that may have crystallized, adding slowly with stirring
1.5 l. of ether. If the product separates as an oil it will soon crystallize on standing. The checkers found that one lot of
75 g. melting at
173–178° when treated in this way gave
67 g. (
89 per cent recovery) melting at
187–189°.
2. If the solution is not clear, it should be filtered before the addition of
pyridine.
3. Discussion
Copyright © 1921-2002, Organic Syntheses, Inc. All Rights Reserved