(Hive Addict)
02-06-03 12:51
No 405196
(Rated as: excellent)
this actually comes from another thread, but that thread is hundreds of posts long, so this the start of a different thread for this patent.
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Patent US3970700
Racemization of Optically Active Amines
Abstract:
A method for racemization of optically active amines which comprises contacting an optically active amine of the formula: ##EQU1## wherein C* is an asymmetric carbon atom, R.sub.1 is alkyl, aralkyl or aryl and R.sub.2 is aryl or alkoxycarbonyl, the aryl or aralkyl moiety bearing optionally one or more alkyl or alkoxy groups on the aromatic ring, provided that R.sub.1 and R.sub.2 are always different from each other, with an alkali metal catalyst selected from the group consisting of (1) an alkali metal deposited on a solid carrier, (2) an alkali metal dispersed in a liquid medium and (3) an alkali metal alloy at a temperature of from -10.degree. to 50.degree.C until a sufficient amount of the optically active amine is recemized.
References Cited:
Patent US3168566
Preparation of Catalyst A:
Catalyst A may be prepared by depositing the alkali metal on a solid carrier such as alumina, silica gel, aluminum silicate, magnesium silicate or activated carbon. The solid carrier is preferred to have a surface area of at least about 25 m.sup.2 per 1 gram, and a higher surface area is more effective. For preparation of a suitable catalyst, the deposition of the alkali metal on the solid carrier is effected at a temperature higher than the melting point of the alkali metal under the atmosphere of an inert gas such as nitrogen, helium or argon. Particularly when alumina is employed as the solid carrier, a highly active catalyst can be obtained by making the deposition at a temperature of from 200.degree. to 500.degree.C. The amount of the alkali metal to be used is usually from 1 to 30% by weight, favorably from 4 to 20% by weight, based on the weight of the solid carrier. The catalyst of this type is known as a catalyst effective in the isomerization of olefins such as butenes J.Am.Chem.Soc., 82, 387 (1960).
Preparation of Catalyst B:
Catalyst B may be prepared by dispersing the alkali metal into a liquid medium such as toluene, xylene or mineral oil. The suitable dispersing medium is inactive for the alkali metal and has a boiling point higher than the melting point of the alkali metal. For preparation of a suitable catalyst, the alkali metal is dispersed into the liquid medium at a temperature higher than the melting point of the alkali metal with stirring. The amount of the alkali metal to be dispersed is usually from 20 to 60% by weight based on the combined weight of the alkali metal and the liquid medium.
Preparation of Catalyst C:
Catalyst C is an alkali metal alloy which is liquid at the process conditions, such as sodium-potassium alloy. In case of sodium-potassium alloy, for instance, the alloy containing 22 to 95% by weight of potassium has a melting point lower than 50.degree.C and the alloy containing 77% by weight of potassium has a melting point of -12.degree.C. The racemization proceeds very easily by stirring the reaction mixture when the alkali metal alloy mentioned above is used as a catalyst in the reaction temperature range of from about -10.degree. to 50.degree.C.
Part I
Under this Part, the examples of the racemization by the use of Catalyst A are shown. The catalysts as used were prepared as follows:
Procedure A
In a 200 ml flask, alumina of 200 to 300 mesh in particle size (100 g) calcined at 500.degree.C for 2 hours was charged and heated at 400.degree.C under a nitrogen atmosphere while stirring. After the addition of metallic sodium (10 g) at the same temperature as above, the resultant mixture was stirred for one hour to give a catalyst (i.e. an alkali metal deposited on a solid carrier).
Procedure B
As in Procedure A, there was prepared a catalyst from alumina (100 g) and metallic potassium (6 g) by heating at 200.degree.C.
Procedure C
As in Procedure A, there was prepared a catalyst from alumina (100 g) and metallic potassium (5 g) by heating at 200.degree.C.
Example 1:
In a 50 ml flask, 25 g of (+)-.alpha.-(1-naphthyl)ethylamine ([.alpha.].sub.D.sup.20 +81.3.degree. (neat)) was charged under nitrogen, and the catalyst prepared as in Procedure A (5.0 g) was added thereto. The resulting mixture was stirred at room temperature. The optical rotation of the reaction mixture measured with elapse of the reaction time was as shown in Table 1.
Table 1
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Reaction time (hrs.) 20
[.alpha.] (c 1, ethanol)
578
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0 +57.1.degree.
1 +30.4.degree.
2 +13.2.degree.
3 +4.6.degree.
5 +1.9.degree.
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The catalyst was filtered off and washed with toluene, and the filtrate was concentrated and then distilled under reduced pressure to give racemic .alpha.-(1-naphthyl)ethylamine (22.4 g). B.P. 124.degree. to 126.degree.C/2.0 mmHg. n.sub.D.sup.20 1.6224.
Example 2:
In a 100 ml reactor, 20 g of (-)-.alpha.-(1-naphthyl)ethylamine ([.alpha.].sub.D.sup.20 -58.2.degree. (neat)) and 30 g of dry toluene were charged under nitrogen, and the catalyst prepared as in Procedure B (4.0 g) was added thereto. The mixture was stirred at 30.degree.C for 4 hours. After filtering off the catalyst, the filtrate was treated as in Example 1 to give 17.3 g of racemic .alpha.-(1-naphthyl)ethylamine. B.P. 102.degree. to 105.degree.C/0.3 mmHg. [.alpha.].sub.D.sup.25 -0.7.degree. (neat).
Example 3:
In a 100 ml flask, 50 g of (+)-.alpha.-phenyl-n-propylamine ([.alpha.].sub.D.sup.25 +21.0.degree. (neat)) was charged under nitrogen, and the catalyst prepared as in Procedure A (3.0 g) was added thereto. The mixture was stirred at 25.degree.C for 7 hours. After filtering off the catalyst, the filtrate was distilled under reduced pressure to give 46.3 g of racemic .alpha.-phenyl-n-propylamine. B.P. 99.degree. to 100.degree.C/16 mmHg. [.alpha.].sub.D.sup.25 +0.1.degree. (neat).
Example 4:
In a 100 ml flask, 50 g of (-)-.alpha.-(p-tolyl)ethylamine ([.alpha.].sub.D.sup.25 -34.0.degree. (neat)) was charged under nitrogen, and the catalyst prepared as in Procedure B (3.0 g) was added thereto. The resultant mixture was stirred at 30.degree.C for 5 hours. After filtering off the catalyst, the filtrate was distilled under reduced pressure to give 43.9 g of racemic .alpha.-(p-tolyl)ethylamine. B.P. 100.degree. to 102.degree.C/17 mmHg. [.alpha.].sub.D.sup.25 -0.3.degree. (neat).
Example 5:
In a 50 ml flask, 20.0 g of (-)-.alpha.-phenyl-.beta.-(p-tolyl)ethyl
Table 2
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Reaction time (hrs.) 25
[.alpha.] (neat)
D
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0 -12.5.degree.
1 -10.9.degree.
2 -5.8.degree.
3 -2.6.degree.
5 -1.2.degree.
7 -0.6.degree.
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After filtering off the catalyst, the filtrate was distilled under reduced pressure to give racemic .alpha.-phenyl-.beta.-(p-tolyl)ethylamin
Example 6:
In a 100 ml flask, 20 g of (-)-.alpha.-phenyl-.beta.-(p-tolyl)ethyl
Example 7:
In a 50 ml flask, 50 g of L-.beta.-phenylalanine methyl ester ([.alpha.].sub.D.sup.25 +22.3.degree. (neat)) was charged under nitrogen, and the catalyst prepared as in Procedure A (3.7 g) was added thereto. The mixture was stirred at 25.degree.C. The optical rotation of the reaction mixture measured with elapse of the reaction time was shown in Table 3.
Table 3
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Reaction time (min.) 25
[.alpha.] (c 1, ethanol)
D
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0 +27.6.degree.
30 +22.3.degree.
60 +16.1.degree.
120 +8.3.degree.
160 +3.5.degree.
240 +0.3.degree.
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After filtering off the catalyst, the filtrate was distilled to give 42.5 g of racemic .beta.-phenylalanine methyl ester. B.P. 90.degree. to 92.degree.C/0.3 mmHg. [.alpha.].sub.D.sup.25 +0.2.degree. (neat).
(Hive Addict)
02-06-03 12:52
No 405197
Example 8:
In a 25 ml flask, 12.0 g of L-leucine ethyl ester was charged under nitrogen, and the catalyst prepared as in Procedure B (1.8 g) was added thereto. The mixture was stirred at 20.degree.C for 5 hours. After filtering off the catalyst, the filtrate was distilled under reduced pressure to give 10.3 g of racemic leucine ethyl ester. B.P. 83.degree. to 84.degree.C/12 mmHg. [.alpha.].sub.D.sup.20 +0.3.degree. (neat).
Example 9:
In a 25 ml flask, 10 g of L-diethyl aspartate ([.alpha.].sub.D.sup.25 -9.5.degree. (neat)) was charged under nitrogen, and the catalyst prepared as in Procedure A (1.7 g) was added thereto. The mixture was stirred at 25.degree.C for 3 hours. After filtering off the catalyst, the filtrate was distilled under reduced pressure to give 9.0 g of racemic diethyl aspartate. B.P. 85.degree. to 86.degree.C/1.0 mmHg. [.alpha.].sub.D.sup.25 -0.4.degree. (neat).
Example 10:
In a 100 ml flask, 20 g of L-.beta.-phenylalanine methyl ester ([.alpha.].sub.D.sup.25 +22.3.degree. (neat)) and 20 g of dry toluene were charged under nitrogen, and the catalyst prepared as in Procedure A (2.0 g) was added thereto. The mixture was stirred at 30.degree.C for 5 hours. After filtering off the catalyst, toluene was distilled off, and the residual solution was distilled under reduced pressure to give 17.0 g of racemic .beta.-phenylalanine methyl ester. B.P. 90.degree. to 92.degree.C/0.3 mmHg. [.alpha.].sub.D.sup.25 +0.3.degree. (neat).
Part II
Under this Part, the examples of the racemization by the use of Catalyst B are shown.
Example 11:
In a 25 ml flask, 10 g of (-)-.alpha.-phenylethylamine ([.alpha.].sub.D.sup.20 -39.degree. (neat)) was charged under nitrogen, and 40% sodium dispersion in liquid paraffin (0.2 g) was added thereto. The mixture was stirred at 25.degree.C for 5 hours. Then, a small amount of ethanol was added to the reaction mixture, whereby the catalyst was inactivated. After the addition of water, the resultant mixture was extracted with toluene. The toluene extract was concentrated and distilled under reduced pressure to give 8.8 g of racemic .alpha.-phenylethylamine. B.P. 105.degree. to 107.degree.C/53 mmHg. [.alpha.].sub.D.sup.25 -0.2.degree. (neat). n.sub.D.sup.20 1.5253.
Example 12:
In a 25 ml flask, 10 g of L-alanine ethyl ester ([.alpha.].sub.D.sup.20 -2.3.degree. (neat)) was charged under nitrogen, and 40% sodium dispersion in liquid paraffin (0.15 g) was added thereto. The mixture was stirred at 27.degree.C for 3 hours. Then, the reaction mixture was treated as in Example 11 to give 8.7 g of racemic alanine ethyl ester. B.P. 48.degree. to 52.degree.C/20 mmHg. [.alpha.].sub.D.sup.20 0.degree. (neat).
Example 13:
In a 25 ml flask, 10 g of (-)-.beta.-phenyl-.alpha.-(p-tolyl)ethyl
Part III
Under this Part, the examples of the racemization by the use of Catalyst C are shown.
EXAMPLE 14
In a 25 ml flask, 10 g of (+)-.alpha.-(1-naphthyl)ethylamine ([.alpha.].sub.D.sup.20 +81.3.degree. (neat)) was charged under nitrogen, and sodium-potassium alloy (Na : K = 56 : 44 by weight) (0.1 g) was added thereto. The mixture was stirred at 20.degree.C for 3 hours. The reaction mixture was treated as in Example 11 to give 9.3 g of racemic .alpha.-(1-naphthyl)ethylamine. B.P. 124.degree. to 126.degree.C/2.0 mmHg. [.alpha.].sub.D.sup.25 -0.2.degree. (neat).
Example 15:
In a 25 ml flask, 10 g of (+)-.alpha.,.beta.-diphenylethylamine ([.alpha.].sub.D.sup.25 +13.4.degree. (neat)) was charged under nitrogen, and sodium-potassium alloy (Na : k = 56 : 44 by weight) (0.1 g) was added thereto. The mixture was stirred at 25.degree.C for 2 hours. The reaction mixture was treated as in Example 11 to give 9.5 g of racemic .alpha.,.beta.-diphenylethylamine. B.P. 114.degree. to 116.degree.C/0.3 mmHg. [.alpha.].sub.D.sup.25 +0.1.degree. (neat). n.sub.D.sup.25 1.5770.
Example 16:
In a 100 ml flask, 50 g of (+)-.alpha.-phenyl-.beta.-(p-tolyl)ethyl
Example 17:
In a 25 ml flask, 13.0 g of D-.beta.-phenylalanine ethyl ester was charged under nitrogen, and sodium-potassium alloy (Na : K = 56 : 44 by weight) (0.1 g) was added thereto. The mixture was stirred at 20.degree.C for 3 hours. The reaction mixture was treated as in Example 11 to give 12.1 g of racemic .beta.-phenylalanine ethyl ester. B.P. 95.degree. to 96.degree.C/0.6 mmHg. [.alpha.].sub.D.sup.25 -0.1.degree. (neat).