US2727061A - Process for preparing in a selective man- - Google Patents
Process for preparing in a selective man- Download PDFInfo
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- US2727061A US2727061A US2727061DA US2727061A US 2727061 A US2727061 A US 2727061A US 2727061D A US2727061D A US 2727061DA US 2727061 A US2727061 A US 2727061A
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- Prior art keywords
- nitrophenyl
- amino
- hydrochloride
- propanediol
- separating
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- 238000004519 manufacturing process Methods 0.000 title claims description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 68
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 30
- 229960000583 Acetic Acid Drugs 0.000 claims description 22
- WETWJCDKMRHUPV-UHFFFAOYSA-N Acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 22
- 239000012346 acetyl chloride Substances 0.000 claims description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- 239000012362 glacial acetic acid Substances 0.000 claims description 12
- 239000000047 product Substances 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 10
- JXTHNDFMNIQAHM-UHFFFAOYSA-N Dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 claims description 8
- 229960005215 dichloroacetic acid Drugs 0.000 claims description 8
- FBCCMZVIWNDFMO-UHFFFAOYSA-N dichloroacetyl chloride Chemical compound ClC(Cl)C(Cl)=O FBCCMZVIWNDFMO-UHFFFAOYSA-N 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 8
- 239000000376 reactant Substances 0.000 claims description 8
- 238000007865 diluting Methods 0.000 claims description 6
- 239000002244 precipitate Substances 0.000 claims description 6
- JHFPTBDSRTUDGQ-UHFFFAOYSA-N (3-amino-3-hydroxypropyl) acetate Chemical compound CC(=O)OCCC(N)O JHFPTBDSRTUDGQ-UHFFFAOYSA-N 0.000 claims 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 12
- 235000011054 acetic acid Nutrition 0.000 description 10
- 125000002252 acyl group Chemical group 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 8
- 230000005012 migration Effects 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 238000005917 acylation reaction Methods 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-M chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000012047 saturated solution Substances 0.000 description 6
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M NaHCO3 Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 230000005591 charge neutralization Effects 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 150000003840 hydrochlorides Chemical class 0.000 description 4
- 239000000155 melt Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000001264 neutralization Effects 0.000 description 4
- 238000006386 neutralization reaction Methods 0.000 description 4
- 238000007127 saponification reaction Methods 0.000 description 4
- 229960005091 Chloramphenicol Drugs 0.000 description 2
- WIIZWVCIJKGZOK-RKDXNWHRSA-N Chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 2
- XKRSUFASZHWBMK-UHFFFAOYSA-N ClC(C(=O)NC(CCO)O)Cl Chemical compound ClC(C(=O)NC(CCO)O)Cl XKRSUFASZHWBMK-UHFFFAOYSA-N 0.000 description 2
- RXKJFZQQPQGTFL-UHFFFAOYSA-N Dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- SUYYUQAZZGDCPV-UHFFFAOYSA-N [1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]azanium;chloride Chemical compound Cl.OCC(N)C(O)C1=CC=C([N+]([O-])=O)C=C1 SUYYUQAZZGDCPV-UHFFFAOYSA-N 0.000 description 2
- PQXSIWRVNQFSSI-UHFFFAOYSA-N [N+](=O)([O-])C(C(O)(O)NC1=CC=CC=C1)C Chemical class [N+](=O)([O-])C(C(O)(O)NC1=CC=CC=C1)C PQXSIWRVNQFSSI-UHFFFAOYSA-N 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000004432 carbon atoms Chemical group C* 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000000875 corresponding Effects 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 2
- 235000019256 formaldehyde Nutrition 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 230000003472 neutralizing Effects 0.000 description 2
- 238000006396 nitration reaction Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000002194 synthesizing Effects 0.000 description 2
- 238000005292 vacuum distillation Methods 0.000 description 2
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C215/04—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated
- C07C215/06—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic
- C07C215/10—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic with one amino group and at least two hydroxy groups bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Definitions
- acylation is carried out at a temperature lower than 40 (1., operating under anhydrous conditions, While the 0,0- diacylic hydrochlorides thus obtained, and separated if so desired, are alkalized, after previous addition of water, to pH lower than 8 to obtain the N,O-diacyl derivatives, or to pH higher than 8, after previously diluting the watery mixture with an organic solvent miscible with water, such as an alcohol, an aliphatic ketone or a cyclic Patented Dec.
- an organic solvent miscible with water such as an alcohol, an aliphatic ketone or a cyclic Patented Dec.
- nitrophenylaminopropanediols as they contain two asymmetric adjacent carbon atoms, can exist in the following six forms; erythro (or regular or cis), threo (pr pseudo 0) or trans), and for each of these in the dextrorotatory, laevorotatory and racenu'c forms; it is understood, therefore, that in the present specification and appended claims, where not otherwise indicated, any of said forms is referred to.
- Example 1 g. of threo-l-p.nitrophenyl-2-amino-1,3-propanediol are dissolved in cc. of glacial acetic acid, and cc. of saturated solution of hydrochloric acid in glacial acetic acid (about 8.5 and 15 cc. of acetyl chloride are added. After one night, dilution is elfected with ether, and threo-1-p.nitrophenyl-1,3-diacetoxy-2-aminopropanc hydrochloride M. P. l59161 C is obtained.
- Example 2 10 g. of erythro-l-p.nitrophenyl-2-amino-l,3-propanediol hydrochloride are suspended in a mixture of 10 cc. of saturated solution of hydrochloric acid in acetic acid plus 10 cc. of acetyl chloride. Stirring is efiected during 15 hours and then filtering-0E is eiiected from erythro- 1-p.nitrophenyl-1,3-diacetoXy-2-aminopropane hydrochloride M. P. 166469 C. formed.
- Example 3 10 g. of L-(+)-l-p.nitrophenyl-2-amino-1,3-propanediol are suspended in 24 cc. of saturated solution of hydrochloric acid in acetic acid (about 11%) and 16 cc. of acetyl chloride are added.
- Example 4 10 g. of D-(-)-1-p.nitrophenyl-2-amino-1,3-propanediol hydrochloride are suspended in 10 cc. of dichloro- RCOCZI/ N07.C6H4.CH(O COR).CH(NH2.HC1).CH2O 0 OR NO2.CuH4.CHOH.CH(NH.C OR).CH:OH
- aceticacid'and '10 cc. of 'dichloroacetyl chloride are added. After one night under agitation the mixture is cooled to 0 .C. Ice and an equal volume of acetone are added and the watery mixture thus obtained'is brought to pH 8'9with 10% sodium hydroxide. It is then left at a temperature of 0 C. 'for two hours. Then neutralization 'withHCl UN and distillation of the acetone under vacuum are effected.
- A' process for preparing acetylated derivatives of 1:p-nitrophenyl-Z-amino-l,3-propanediol which comprises treating, under anhydrous conditions and at a temperature not higherthan 40 C., l-p-hitrophenyl-Z-aminol,3-pi'opanediol hydrochloride with a reactant saturated With gaseous hydrochloric acid and selected from the group consisting of acetyl chloride dissolved in acetic acid and dichl'oroacetyl chloride dissolved in dichloroacetic acid, separating 'the resulting l-p-nitrophenyl-1,3- diace'toxy-2-amino-propane hydrochloride, dissolving it in'water, adding an organic solvent miscible with water, adjusting the pH value to above 7 while keeping the temperature between 0 and 30 C., and separating the resulting crystalline product.
- a process for preparing N,O-diacetylated derivatives of l-p-nitrophenyl-Z-amino-1,3-propanediol which comprises treating, under anhydrous conditions and at a temperature not higher than 40 C., 1-p-nitrophenyl-2- amino*l-,3 -propanediol hydrochloride with a reactant saturated with gaseous hydrochloric acid and selected from the group consisting of acetyl chloride dissolved in acetic acid anddichloroacetyl chloride dissolved in dichloroacetic acid, separating the resulting 1-p-nitrophenyl-l,3-diacetoxy-Z-amino-propane hydrochloride, dissolving it in water, adjusting the pH value to between 7 and 8, and separating the resulting crystalline product.
- a process for preparing threo-l-p-nitrophefiyl-Z- acetyl amino-3-acetoxypropane-1-ol which comprises dissolving threo-l-p-nitrophenyl-2-amino-1,3-propanediol in glacial acetic acid, adding glacial acetic acid saturated with gaseous hydrochloric acid and acetyl chloride, permitting to stand for abouftwelve'hou'rs, diluting with ether, separating the resulting threo-1-p-nitropheny1-1,3- diacetoxy-Z-aminopropane hydrochloride, dissolving it in water, adjusting the pH value between Tend 8, and se'pa rating the oily precipitate which crystallizes at once.
- a process for preparing D-(+)-1'-p-nitrophenyl-2 dichloroacetylamino-1,3-propanediol which comprises suspending D- -1-p-nitrophenyl-2-amino-Lil-propanediol hydrochloride in dichloroacetic acid to which dichloroacetyl chloride has been added, agitating forabo'ut twelve hours, cooling to 0 C., adding ice and anequal volume of acetone, adjusting the pH value to between 8 and 9 with a 10% sodium hydroxide solution, neutralizing with 1N hydrochloric acid, removing acetone by vacuum distillation and separating the resulting crystalline product.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
United States Patent "'ice PROCESS FOR PREPARING IN A SELECTIVE MAN NER MONO- AND DI-ACYL DERIVATIVES F 1-p.NI'I'ROPHENYL-2-AMINO-1,3-PROPANEDIOI S Alberto Vercellone and Carlo Giuseppe Alberta, Milan,
Italy, assignors to Farmaceutici Italia S. A., a corporation of Italy No Drawing. Application August 29, 1951, Serial No. 244,275
Claims priority, application Italy May 30, 1951 7 Claims. (Cl. 260-490) As is known, 1-p.nitrophenyl-2-amino-1,3-propanediols have three functional groups adapted to be acylated; therefore, the importance is evident of finding a method enabling to obtain in a selective manner only the respective monoor di-acyl derivatives, which ofier particular interest for the synthesis of chloramphenicol.
Applicants have in fact already claimed the preparation of said monoand di-acyl derivatives by means of a selective acylation of 1-phenyl-2-arnino-1,3-propanediols, followed by the nitration of the compounds obtained and by the subsequent migration of an acyl group from O to N (applicants copending applications, Serial Nos. 244,273 and 244,274, filed August 29, 1951).
It has now been found that the aforesaid operations of acylation in a selective manner and migration of an acyl group from O to N, optionally with contemporaneous partial saponification, are applicable also to already nitrated starting products, that is to say to 1-p.nitrophenyl-Z-amino-1,3-propanediols.
It is therefore the object of the present invention to provide a process for preparing selectively monoand diacyl derivatives of 1-p.nitrophenyl-2-amino-1,3-propanediols, in particular N-monoacyland N,O-diacyl derivatives, which is essentially characterized by the fact that 1-p.nitrophenyl-2-amino-l,3-propanediols are treated with the chloride of an acid dissolved in the corresponding acid, saturated with hydrochloric acid, and that the 0,0-diacylic hydrochlorides thus obtained are subjected to the simple migration of an acyl group to N, to obtain the N,O-diacyl derivatives, or to said migration with contemporaneous saponification of the other acyl group, to obtain the N-monoacyl derivatives.
In particular, according to the present invention, acylation is carried out at a temperature lower than 40 (1., operating under anhydrous conditions, While the 0,0- diacylic hydrochlorides thus obtained, and separated if so desired, are alkalized, after previous addition of water, to pH lower than 8 to obtain the N,O-diacyl derivatives, or to pH higher than 8, after previously diluting the watery mixture with an organic solvent miscible with water, such as an alcohol, an aliphatic ketone or a cyclic Patented Dec. 13, 1955 As is known, nitrophenylaminopropanediols, as they contain two asymmetric adjacent carbon atoms, can exist in the following six forms; erythro (or regular or cis), threo (pr pseudo 0) or trans), and for each of these in the dextrorotatory, laevorotatory and racenu'c forms; it is understood, therefore, that in the present specification and appended claims, where not otherwise indicated, any of said forms is referred to.
The following examples of the invention are given by way of illustration without limitation.
Example 1 g. of threo-l-p.nitrophenyl-2-amino-1,3-propanediol are dissolved in cc. of glacial acetic acid, and cc. of saturated solution of hydrochloric acid in glacial acetic acid (about 8.5 and 15 cc. of acetyl chloride are added. After one night, dilution is elfected with ether, and threo-1-p.nitrophenyl-1,3-diacetoxy-2-aminopropanc hydrochloride M. P. l59161 C is obtained.
15 g. of said hydrochloride are dissolved in 60 cc. of water and alkalization is effected with 5 g. of sodium bicarbonate. At first an oil precipitates, which crystallizes at once. Filtration and drying is effected and threo-lp.nitrophenyl-Z-acetylamino-3-acetoxypropan-1-ol M. P. 162-163 C. is obtained.
Example 2 10 g. of erythro-l-p.nitrophenyl-2-amino-l,3-propanediol hydrochloride are suspended in a mixture of 10 cc. of saturated solution of hydrochloric acid in acetic acid plus 10 cc. of acetyl chloride. Stirring is efiected during 15 hours and then filtering-0E is eiiected from erythro- 1-p.nitrophenyl-1,3-diacetoXy-2-aminopropane hydrochloride M. P. 166469 C. formed.
13 g. of said hydrochloride are dissolved in cc. of water, cc. of acetone and then, at 0 C., 25 cc. of NaOH N/2 are added. After two hours, neutralization is effected at 0 C. with HCl N/ 1 and the acetone is distilled under vacuum.
By filtration, the erythro-1-p.nitrophenyl-Z-acetylamino- 1,3-propanediol M. P. 192 C. is obtained.
Example 3 10 g. of L-(+)-l-p.nitrophenyl-2-amino-1,3-propanediol are suspended in 24 cc. of saturated solution of hydrochloric acid in acetic acid (about 11%) and 16 cc. of acetyl chloride are added.
After one night, filtration is efiected from the L-(+)- 1-p.nitrophenyl-l,3-diacetoXy-2-aminopropane hydrochloride, which purified from methanol-ether has a M. P. 172 C. and (a) =+6.5 (methanol; c=4.18).
15 g. of said hydrochloride are dissolved in 60 cc. of water and further proceeding is effected as indicated in Example 1. The L-()-l-p.nitrophenyl-Z-acetylamino- 3-acetoxypropan-l-ol is obtained, which purified from ethyl acetate melts at l34136 C. with (a) =19.7 (methanol; c=3.86).
Example 4 10 g. of D-(-)-1-p.nitrophenyl-2-amino-1,3-propanediol hydrochloride are suspended in 10 cc. of dichloro- RCOCZI/ N07.C6H4.CH(O COR).CH(NH2.HC1).CH2O 0 OR NO2.CuH4.CHOH.CH(NH.C OR).CH:OH
aceticacid'and '10 cc. of 'dichloroacetyl chloride are added. After one night under agitation the mixture is cooled to 0 .C. Ice and an equal volume of acetone are added and the watery mixture thus obtained'is brought to pH 8'9with 10% sodium hydroxide. It is then left at a temperature of 0 C. 'for two hours. Then neutralization 'withHCl UN and distillation of the acetone under vacuum are effected.
'By filtration, the D-(+)-l-p.nitrophenyl-2-dichloroacetylamino-1,3-propanediol is collected, which re-crystallized from water melts at 149-l50 C. with (a) :+19 (ethanol; 'c-"-'5) We claim:
1. A' process for preparing acetylated derivatives of 1:p-nitrophenyl-Z-amino-l,3-propanediol, which comprises treating, under anhydrous conditions and at a temperature not higherthan 40 C., l-p-hitrophenyl-Z-aminol,3-pi'opanediol hydrochloride with a reactant saturated With gaseous hydrochloric acid and selected from the group consisting of acetyl chloride dissolved in acetic acid and dichl'oroacetyl chloride dissolved in dichloroacetic acid, separating 'the resulting l-p-nitrophenyl-1,3- diace'toxy-2-amino-propane hydrochloride, dissolving it in'water, adding an organic solvent miscible with water, adjusting the pH value to above 7 while keeping the temperature between 0 and 30 C., and separating the resulting crystalline product.
2. A process for preparing N,O-diacetylated derivatives of l-p-nitrophenyl-Z-amino-1,3-propanediol, which comprises treating, under anhydrous conditions and at a temperature not higher than 40 C., 1-p-nitrophenyl-2- amino*l-,3 -propanediol hydrochloride with a reactant saturated with gaseous hydrochloric acid and selected from the group consisting of acetyl chloride dissolved in acetic acid anddichloroacetyl chloride dissolved in dichloroacetic acid, separating the resulting 1-p-nitrophenyl-l,3-diacetoxy-Z-amino-propane hydrochloride, dissolving it in water, adjusting the pH value to between 7 and 8, and separating the resulting crystalline product.
3. A process according to claim 2, wherein the free base of 1-p-nitrophenyl-2-amino-l,3-propanediol is used insteadof t'he hydrochloride.
4. A process for preparing N-monoacetylated derivatives of l-p-nitrophenyl-Z-amino-1,3-propanediol, which comprises treating, under anhydrous conditions and at a temperature not higher than 40 C., 1-p-nitrophenyl-2- amino-1,3-propanediol hydrochlorid: with a reactant saturated'with gaseous hydrochloric acid and selected from the group consisting of acetyl chloride dissolved in acetic acid and dichloroacetyl chloride dissolved in =dichlomacetic acid, separating the resulting 1-p-nitrophenyl-1,3- diacetoxy-Z-aminopropane hydrochloride, dissolving it in water, adding an organic solvent miscible with water, adjusting the pH value to above 8 while'keeping the ternperature between 0 and 30C., and separating the resulting crystalline product. 7
5. A process according to claim 4, wherein the free base of l-p-nitrophenyl-Z-amino-1,3-propanediol is used instead of the hydrochloride. 7
6. A process for preparing threo-l-p-nitrophefiyl-Z- acetyl amino-3-acetoxypropane-1-ol, which comprises dissolving threo-l-p-nitrophenyl-2-amino-1,3-propanediol in glacial acetic acid, adding glacial acetic acid saturated with gaseous hydrochloric acid and acetyl chloride, permitting to stand for abouftwelve'hou'rs, diluting with ether, separating the resulting threo-1-p-nitropheny1-1,3- diacetoxy-Z-aminopropane hydrochloride, dissolving it in water, adjusting the pH value between Tend 8, and se'pa rating the oily precipitate which crystallizes at once.
7. A process for preparing D-(+)-1'-p-nitrophenyl-2 dichloroacetylamino-1,3-propanediol, which comprises suspending D- -1-p-nitrophenyl-2-amino-Lil-propanediol hydrochloride in dichloroacetic acid to which dichloroacetyl chloride has been added, agitating forabo'ut twelve hours, cooling to 0 C., adding ice and anequal volume of acetone, adjusting the pH value to between 8 and 9 with a 10% sodium hydroxide solution, neutralizing with 1N hydrochloric acid, removing acetone by vacuum distillation and separating the resulting crystalline product.
References Cited in the file of this patent UNITED STATES PATENTS 2,483,884 Crooks et al. 'Oct.'4, .1949 2,483,885 Crooks et al. Oct. 4, 1 949 2,538,764 Crooks et al. -Ian.'23, 1951 2,538,765 Crooks et al. Jan. 23, 1'95-1 OTHER REFERENCES Rebstock et al.: I. Am. Chem. Soc. vol. 71 (1949)., p.246l.
Controvlis et al.: J. Am. Chem. Soc. vol. 71 (1949.), p. 2468.
Phillips et al.: I. Am. Chem. Soc. vol. 72 1950), pp. 4920-21.
Phillips et al.: I. Am. Chem. Soc. vol- 69 (1947.), pp. 203-4.
Claims (2)
1. A PROCESS FOR PREPARING ACETYLATED DERIVATIVES OF 1-P-NITROPHENYL-2-AMINO-1,3-PROPANEDIOL, WHICH COMPRISES TREATING UNDER ANHYDROUS CONDITIONS AND AT A TEMPERATURE NOT HIGHER THAN 40* C., 1-P-NITROPHENYL-2-AMINO1,3-PROPANEDIOL HYDROCHLORIDE WITH A REACTANT SATURATED WITH GASEOUS HYDROCHLORIDE ACID AND SELECTED FROM THE GROUP CONSISTING OF ACETYL CHLORIDE DISSOLVED IN ACETIC ACID AND DICHLOROACETYL CHLORIDE DISSOLVED IN DICHLOROACETIC ACID, SEPARATING THE RESULTING 1-P-NITROPHENYL-1,3DIACETOXY-2-AMINO-PROPANE HYDROCHLORIDE, DISSOLVING IT IN WATER, ADDING AN ORGANIC SOLVENT MISCIBLE WITH WATER, ADJUSTING THE PH VALUE OF ABOUT 7 WHILE KEEPING THE TEMPERATURE BETWEEN 0 TO 30* C., AND SEPARATING THE RESULTING CRYSTALLINE PRODUCT.
6. A PROCESS FOR PREPARING THREO-1-P-NITROPHENYL-2ACETYL AMINO-3-ACETOXYPROPANE-1-OL, WHICH COMPRISES DISSOLVING THREO-1-P-NITROPHENYL-2-AMINO-1,3-PROPANEDIOL IN GLACIAL ACETIC ACID, ADDING GLACIAL ACETIC ACID SATURATED WITH GASEOUS HYDROCHLORIDE ACID AND ACETYL CHLORIDE, PERMITTING TO STAND FOR ABOUT TWELVE HOURS, DILUTING WITH ETHER, SEPARATING THE RESULTING THREO-1-P-NITROPHENYL -1,3DIACETOXY-2-AMINOPROPANE HYDROCHLORIDE, DISSOLVING IT IN WATER, ADJUSTING THE PH VALUE BETWEEN 7 AND 8, AND SEPARATING THE OILY PRECIPITATE WHICH CRYSTALLIZES AT ONCE.
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US2727061A true US2727061A (en) | 1955-12-13 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US2727061D Expired - Lifetime US2727061A (en) | Process for preparing in a selective man- |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3100781A (en) * | 1957-11-20 | 1963-08-13 | Zambon Spa | Chloramphenicol glycinate and the production thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2483885A (en) * | 1949-02-12 | 1949-10-04 | Parke Davis & Co | Nitrophenyl acyl amido alkane diols |
| US2483884A (en) * | 1948-03-16 | 1949-10-04 | Parke Davis & Co | Method for making nitrophenyl acylamido alkane diols |
| US2538764A (en) * | 1949-02-12 | 1951-01-23 | Parke Davis & Co | Acylamido-phenylpropanediols |
| US2539765A (en) * | 1947-03-29 | 1951-01-30 | Wold Eleanor | Educational toy |
-
0
- US US2727061D patent/US2727061A/en not_active Expired - Lifetime
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2539765A (en) * | 1947-03-29 | 1951-01-30 | Wold Eleanor | Educational toy |
| US2483884A (en) * | 1948-03-16 | 1949-10-04 | Parke Davis & Co | Method for making nitrophenyl acylamido alkane diols |
| US2483885A (en) * | 1949-02-12 | 1949-10-04 | Parke Davis & Co | Nitrophenyl acyl amido alkane diols |
| US2538764A (en) * | 1949-02-12 | 1951-01-23 | Parke Davis & Co | Acylamido-phenylpropanediols |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3100781A (en) * | 1957-11-20 | 1963-08-13 | Zambon Spa | Chloramphenicol glycinate and the production thereof |
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