US952006A - Preparation of esters of oxyamino acids. - Google Patents

Preparation of esters of oxyamino acids. Download PDF

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US952006A
US952006A US35446407A US1907354464A US952006A US 952006 A US952006 A US 952006A US 35446407 A US35446407 A US 35446407A US 1907354464 A US1907354464 A US 1907354464A US 952006 A US952006 A US 952006A
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methyl
esters
oxy
acid
amino
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US35446407A
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Ernest Fourneau
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/30—Preparation of optical isomers
    • C07C227/32—Preparation of optical isomers by stereospecific synthesis

Definitions

  • the acid is slightly soluble in Water, stable and has no sweet taste. Melikotf does not descrlbe its esters.
  • Other publications on the oXy-amino acids are those of- I (1) Zelinsky. Journal of the Russian Chemical Society Vol. 16, page 687 in which 1 the methyl amino oxybutyric acid is described. The position of the -NH(CH group is not determined.
  • Egorofl' (Uentmlblatt 1903; II, 555) describes the preparation or" -methyl-oxy-acetic acid CH O p COOH CH3 amino di- NH H by the reduction of the corresponding nitro body obtained by the action of nitrogen peroxid (N 0 on methyl acrylic acid.
  • esters of the ony-amino acids are known except those in which the amino group and hydroxyl group are attached to the same carbon atom. See Kuchert, Berta/ u e 18,618.
  • esters of the amino derivatives of di-methyloxy-acetic acid being stable and distillable without alteration, even at ordinary pressure.
  • the properties of these bodies resemble closely those of the amino derivatives of tertiary alcohols described in the U. S. Patents Nos. 828846 and 829262.
  • the hydrogen of the hydroxyl group is replaceable by acid radicals with formation of esters differing from one another according to the substituting acid used.
  • esters of the oxy-amino acetic acids are obtained 1st by the esterification of the oxy-amino acids, 2nd by the action of the secondary amins on the halogen derivatives of the acid esters such as ot er CHBC-OH ooo m If ammonia and a primary amin be allowed to react in place of the secondary amin an acid amid is also formed, thus with ammonia CHaNHz CHa-(J-OH 0.NH
  • the first method only will be described in this text- Mono-chlor-di-methyl-oxy-acetic acid CH2Cl-C-COOH.
  • amino-di-methyl-oxy-acetic acid are treated with 200 grs. of ethyl alcohol, previously saturated with hydrochloric acid gas, for 2 hours in a flask provided with a reflux condenser: at the end of this time the excess of alcohol and hydrochloric acid is distilled off and the hydrochlorid of the ethyl ester of amino-di-methyl-oxy-acetic acid allowed to crystallize out.
  • the free base or ethyl ester of the above acid is liberated by treating with the requisite quantity of a 10% solution of caustic soda, excess of sodium carbonate is then added until the mass becomes pasty when it is extracted with either chloroform or ether.
  • the ether or chloroform extract is then dried over anhydrous sodium sulfate and the solvent evaporated.
  • the residue is fractionated in 'vacuo.
  • Theethyl ester distils over at 107 to 109 C. under 15 mm. pressure without the least decomposition solidifying to colorless crystals, soluble in alcohol, ether and Water.
  • the hydrochlorid is formed, which after recrystallization from alcohol forms fine needles, very soluble in water, sparingly so in alcohol and insoluble in chloroform and ether, M. P. 105 C.
  • the corresponding urethane is obtained by the action of mono-chlorforlnic ester on the ethyl ester described in Example 1. It boils at 1G4165 C. under 16 mm. pressure. It is soluble in water.
  • Example 2 Methyl ester of di-methylamino-di-methyl-oxy-acetic acid.
  • CHaon The free acid is obtained by the action of di-methylamin on chloro-di-methyl-oxy acetic acid. It forms large hygroscopic crystals neutral toward litmus and of a sweet taste.
  • M. P. 174 C. Its methyl ester is obtained by heating with 4 parts of methyl alcohol saturated with hydrochloric acid. gas. as in the case of Example 1.
  • the base boils at 107 C. under 35 mm. pressure. It is a liquid, soluble in organic solvents and in cold water, but almost insoluble in hot water.
  • Gold chlorid precipitates an oil from its solution in hydrochloric acid. Platinum chlorid however does not do so.
  • the bydrochlorid of its benzoyl derivative crystallizes from a mixture of alcohol and ether in beautiful needles. M. P. 149150 C.
  • Example 5 Ethyl-ester of mono-methylam1no-di-methyl-oxy-acetic acid. 1
  • the corresponding acid which has never been described is prepared like its homor/ logue, using mono methyl-amin in place of di-methyl-amin. It is a crystalline body whose solubilityv and other physical properties are intermediate between those of the ethyl esters of amino-di-methyl-oxy-aceticacid and di methyl amino di methyl oxyacetic acid. Itis neutral to litmus, very ture of acetOnJand water. M. P. 222231 sparingly soluble in absolute alcohol and insolublein acetone. It can be crystallized from a mix- (1, with decomposition.
  • the ethyl ester is obtained by treating the free acid with 4 times its weight of ethyl alcohol saturated with hydrochloric acid. It is isolated as in the previous examples. B. P. 112 C. under 38 mm. pressure.
  • esters of the oxy-amino acids serve principally for preparing acidyl derivatives which are used as local anesthetics, and for other like purposes in medicine.
  • the esters themselves also possess different properties according to the radical used, some of them having hypnotic properties, and they are of particular value in many cases 011 account of the fact that they are but slightly poisonous.
  • esters of oxy-amino acids of the general %ormulain which R zan alkyl group, consisting in treating oxy-amino acids with ethyl alcohol previously saturated with gaseous hydrochloric acid in the cold, heating the mixture, disti ing oil the excess of alcohol and hydrochloric acid, crystallizin out the hydrochlorid, setting free the desired ester by the addition of a caustic soda solution, rendering pasty with sodium carbonate and extracting with ether.
  • dimethyl amilio di methyl oxy acetate of methyl onamcinn CHa-C-OH I (loans. is obtained by warming methyl alcohol saturated with hydrochloric acid gas with the *free di methyl amino di meth l-oxyacetic acid, the resultant product boiling at 107 C. under 35 millimeters pressure, soluble in cold water, almost insoluble in hot 110 water, yielding a benzoyl derivative, the hydrochlorid of which melts at 150 C.

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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Description

UNTTED TATES rnrnn'r canton.
ERNEST FOURNEAU, 0F PARIS, FRANCE.
PREPARATION 0F ESTE No Drawing.
Specification of Letters Patent.
RS 0F GXYAMINQ ACIDS.
To all whom it may concern:
Be it known that l, ERNEST FOURNEAU,
Preparation of the esters of oxy-amino acids of the general formula in which R and R represent either hydrogen or an alkyl group and R represents an allryl group.
.By the action of ammonia on methylglyceric acid an oXy-amino acid is obtained, in which the position of the amino group, probably represented by formula 1 (see below) is not definitely established.
CHnNH CHQOH CHa- -OH 0133- NH COQRZ CO2R See Melikofi", Liebz'gs Annalen 234: 207, and 217. Emma 12, 2227. 13, 95e. 15, 2585. Beilstein I, 1209.
The acid is slightly soluble in Water, stable and has no sweet taste. Melikotf does not descrlbe its esters. Other publications on the oXy-amino acids are those of- I (1) Zelinsky. Journal of the Russian Chemical Society Vol. 16, page 687 in which 1 the methyl amino oxybutyric acid is described. The position of the -NH(CH group is not determined.
(2) Heintz, Liebigs Annalen 192,329, and Weill, Zlz'ebigs Annalen 232,209 in which amino-tri-methyl-oxy-butyric acid is described.
(3) Erlenmeyer and E. Fischer (Bem'chte 1902, 3787) describe the oXy-amino acids obtained by the decomposition of the albuminoids.
(4) Egorofl' (Uentmlblatt 1903; II, 555) describes the preparation or" -methyl-oxy-acetic acid CH O p COOH CH3 amino di- NH H by the reduction of the corresponding nitro body obtained by the action of nitrogen peroxid (N 0 on methyl acrylic acid.
No esters of the ony-amino acids are known except those in which the amino group and hydroxyl group are attached to the same carbon atom. See Kuchert, Berta/ u e 18,618.
on -cooo nt NET-CH3 These bodies are very unstable losing water even at ordinary temperatures.
E. Fischer (Bere'chte 1902, 3787,) and Sorensen, (Uentl'alblatt 1905. H, 100) have investigated the esters of the oXy-amino acids but they have not been able to isolate them owing to the ease with which such esters lose alcohol, two molecules condensing together as shown, giving derivatives of acipiperazm.
aaomomoaco EMF] NH:
cone aomonyon' oacmonmaogat-oe Nnco E. Fischer and Dilthey (Bem'chte 35, 84:4 and 856) after having studied the action of ammonia on the di-alkylmalonic esters and upon the acid esters in which a tertiary car- Patented Mar. 15, 11919. Application filed January 28, 1907. Serial No. 354/164".
bon atom is attached to the CO() H group zins.
lose alcohol and give the di-aci-oxypipera This was found to be the case, all the esters of the amino derivatives of di-methyloxy-acetic acid being stable and distillable without alteration, even at ordinary pressure. The properties of these bodies resemble closely those of the amino derivatives of tertiary alcohols described in the U. S. Patents Nos. 828846 and 829262. In these esters of amino-di-methyl-oxyacetic acids the hydrogen of the hydroxyl group is replaceable by acid radicals with formation of esters differing from one another according to the substituting acid used.
The esters of the oxy-amino acetic acids are obtained 1st by the esterification of the oxy-amino acids, 2nd by the action of the secondary amins on the halogen derivatives of the acid esters such as ot er CHBC-OH ooo m If ammonia and a primary amin be allowed to react in place of the secondary amin an acid amid is also formed, thus with ammonia CHaNHz CHa-(J-OH 0.NH The first method only will be described in this text- Mono-chlor-di-methyl-oxy-acetic acid CH2Cl-C-COOH.
. OH/ forms the primary material for the preparation of these ethers. It is obtained by the action of hydrocyanic acid on mono-chloraceton and subsequent 'saponification of the nitrite so obtained i CH CH CH 3 OH OH OH C=O+H= C and C +2111 O C 0 CN coon-tun. CH CION CHzCl CHzCl CHaCl Example 1: Ethylester of amino-dimethyl-oxy-acetic acid.
CH2-NHz ca d-0H I COO-CgI-h.
50 grs. amino-di-methyl-oxy-acetic acid are treated with 200 grs. of ethyl alcohol, previously saturated with hydrochloric acid gas, for 2 hours in a flask provided with a reflux condenser: at the end of this time the excess of alcohol and hydrochloric acid is distilled off and the hydrochlorid of the ethyl ester of amino-di-methyl-oxy-acetic acid allowed to crystallize out. The free base or ethyl ester of the above acid is liberated by treating with the requisite quantity of a 10% solution of caustic soda, excess of sodium carbonate is then added until the mass becomes pasty when it is extracted with either chloroform or ether. The ether or chloroform extract is then dried over anhydrous sodium sulfate and the solvent evaporated. The residue is fractionated in 'vacuo. Theethyl ester distils over at 107 to 109 C. under 15 mm. pressure without the least decomposition solidifying to colorless crystals, soluble in alcohol, ether and Water.
Treated in ether solution with hydrochloric acid, the hydrochlorid is formed, which after recrystallization from alcohol forms fine needles, very soluble in water, sparingly so in alcohol and insoluble in chloroform and ether, M. P. 105 C. The corresponding urethaneis obtained by the action of mono-chlorforlnic ester on the ethyl ester described in Example 1. It boils at 1G4165 C. under 16 mm. pressure. It is soluble in water.
Example 2: Methyl ester of di-methylamino-di-methyl-oxy-acetic acid.
CHaon The free acid is obtained by the action of di-methylamin on chloro-di-methyl-oxy acetic acid. It forms large hygroscopic crystals neutral toward litmus and of a sweet taste. M. P. 174 C. Its methyl ester is obtained by heating with 4 parts of methyl alcohol saturated with hydrochloric acid. gas. as in the case of Example 1. The base boils at 107 C. under 35 mm. pressure. It is a liquid, soluble in organic solvents and in cold water, but almost insoluble in hot water.
Gold chlorid precipitates an oil from its solution in hydrochloric acid. Platinum chlorid however does not do so. The bydrochlorid of its benzoyl derivative crystallizes from a mixture of alcohol and ether in beautiful needles. M. P. 149150 C.
6(T soluble in water, of a sweet taste Example 3: Ethyl ester of di-methyl-- amino dimethyl-oxy-acetic acid.
di-methyl- 45 grs. amino-di-methyl-oxy-acetic acid are heated with 200 grs. iso-amyl alcohol and 60 grs. gaseous hydrochloric acid for 3 hours on an oil bath in a flask fitted with a reflux condenser. The excess of amyl alcohol is now distilled off under reduced pressure, the residue is dissolved in water and the aqueous solution is extracted with ether to remove the last traces of amyl alcohol. The aqueous solution is then concentrated in @(IKIHO and the free base or iso-amyl ester is liberated by sodium carbonate and extracted byether. The iso-amyl ester boils at 121 (J. under 12 mm. pressure. The yield is about 40 grs. It is almost insoluble in water. The hydrochlorid of its benzoyl derivative is fairlysoluble in benzene. M. 134 C.
Example 5: Ethyl-ester of mono-methylam1no-di-methyl-oxy-acetic acid. 1
The corresponding acid, which has never been described is prepared like its homor/ logue, using mono methyl-amin in place of di-methyl-amin. It is a crystalline body whose solubilityv and other physical properties are intermediate between those of the ethyl esters of amino-di-methyl-oxy-aceticacid and di methyl amino di methyl oxyacetic acid. Itis neutral to litmus, very ture of acetOnJand water. M. P. 222231 sparingly soluble in absolute alcohol and insolublein acetone. It can be crystallized from a mix- (1, with decomposition.
The ethyl ester is obtained by treating the free acid with 4 times its weight of ethyl alcohol saturated with hydrochloric acid. It is isolated as in the previous examples. B. P. 112 C. under 38 mm. pressure.
The esters of the oxy-amino acids, produced according to this invention, serve principally for preparing acidyl derivatives which are used as local anesthetics, and for other like purposes in medicine. The esters themselves also possess different properties according to the radical used, some of them having hypnotic properties, and they are of particular value in many cases 011 account of the fact that they are but slightly poisonous.
I declare that What I claim is 1. The hereinbefore described process for obtainin esters of oxy-amino acids, of the general %ormulain which R zan alkyl group, consisting in treating oxy-amino acids with ethyl alcohol previously saturated with gaseous hydrochloric acid in the cold, heating the mixture, disti ing oil the excess of alcohol and hydrochloric acid, crystallizin out the hydrochlorid, setting free the desired ester by the addition of a caustic soda solution, rendering pasty with sodium carbonate and extracting with ether.
2. As a new article of manufacture, dimethyl amilio di methyl oxy acetate of methyl onamcinn CHa-C-OH I (loans. is obtained by warming methyl alcohol saturated with hydrochloric acid gas with the *free di methyl amino di meth l-oxyacetic acid, the resultant product boiling at 107 C. under 35 millimeters pressure, soluble in cold water, almost insoluble in hot 110 water, yielding a benzoyl derivative, the hydrochlorid of which melts at 150 C.
In witness whereof, I have hereunto signed my name this 14th day of January 1907, .in the presence of two subscribing witnesses.
' ERNEST FOURNEAU.
Witnesses:
ANTONIO MONTEILHET, HANSON C. 00x12.
US35446407A 1907-01-28 1907-01-28 Preparation of esters of oxyamino acids. Expired - Lifetime US952006A (en)

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2501825A (en) * 1946-05-27 1950-03-28 Celanese Corp Hydrogenation of certain alpha, alpha-disubstituted, beta-nitro propionic acid compounds
US2578611A (en) * 1947-12-20 1951-12-11 Mallinckrodt Chemical Works 2, 4-oxazolidinediones
US3539572A (en) * 1966-11-19 1970-11-10 Roehm & Haas Gmbh 2,5-diketo piperazines
US4208204A (en) * 1977-10-07 1980-06-17 Calbiochem-Behring Corp. 3-Hydroxy-3-methylglutaric acid monoamide and derivatives thereof
US4472092A (en) * 1982-08-09 1984-09-18 Schmidt Glenn H Fabrication of metal shell golf club heads
EP0315814A3 (en) * 1987-10-23 1990-09-12 Dow Corning Corporation Methods for forming porous-surfaced polymeric bodies
BE1003949A3 (en) * 1989-10-25 1992-07-22 Dow Corning Sa Making elements bags.

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2501825A (en) * 1946-05-27 1950-03-28 Celanese Corp Hydrogenation of certain alpha, alpha-disubstituted, beta-nitro propionic acid compounds
US2578611A (en) * 1947-12-20 1951-12-11 Mallinckrodt Chemical Works 2, 4-oxazolidinediones
US3539572A (en) * 1966-11-19 1970-11-10 Roehm & Haas Gmbh 2,5-diketo piperazines
US4208204A (en) * 1977-10-07 1980-06-17 Calbiochem-Behring Corp. 3-Hydroxy-3-methylglutaric acid monoamide and derivatives thereof
US4472092A (en) * 1982-08-09 1984-09-18 Schmidt Glenn H Fabrication of metal shell golf club heads
EP0315814A3 (en) * 1987-10-23 1990-09-12 Dow Corning Corporation Methods for forming porous-surfaced polymeric bodies
BE1003949A3 (en) * 1989-10-25 1992-07-22 Dow Corning Sa Making elements bags.

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