WO2001047856A1 - Process for the recovery and recycle of d-tartaric acid - Google Patents
Process for the recovery and recycle of d-tartaric acid Download PDFInfo
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- WO2001047856A1 WO2001047856A1 PCT/EP2000/012946 EP0012946W WO0147856A1 WO 2001047856 A1 WO2001047856 A1 WO 2001047856A1 EP 0012946 W EP0012946 W EP 0012946W WO 0147856 A1 WO0147856 A1 WO 0147856A1
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- Prior art keywords
- tartrate
- acid
- process according
- tartaric acid
- amino
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 38
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 title claims abstract description 37
- 229960001270 d- tartaric acid Drugs 0.000 title claims abstract description 36
- 238000011084 recovery Methods 0.000 title claims abstract description 16
- CAOHBROWLMCZRP-UHFFFAOYSA-N 2-amino-2,3-dimethylbutanenitrile Chemical compound CC(C)C(C)(N)C#N CAOHBROWLMCZRP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000002253 acid Substances 0.000 claims abstract description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 43
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
- 239000002699 waste material Substances 0.000 claims description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- 239000002904 solvent Substances 0.000 claims description 15
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 14
- 229910052783 alkali metal Inorganic materials 0.000 claims description 14
- -1 alkali metal hydrogen D-tartrate Chemical class 0.000 claims description 11
- FEWJPZIEWOKRBE-LWMBPPNESA-N levotartaric acid Chemical class OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 claims description 11
- CAOHBROWLMCZRP-LURJTMIESA-N (2r)-2-amino-2,3-dimethylbutanenitrile Chemical compound CC(C)[C@@](C)(N)C#N CAOHBROWLMCZRP-LURJTMIESA-N 0.000 claims description 8
- FEWJPZIEWOKRBE-LWMBPPNESA-M D-tartrate(1-) Chemical class OC(=O)[C@@H](O)[C@H](O)C([O-])=O FEWJPZIEWOKRBE-LWMBPPNESA-M 0.000 claims description 6
- 150000001340 alkali metals Chemical class 0.000 claims description 6
- FEWJPZIEWOKRBE-LWMBPPNESA-L D-tartrate(2-) Chemical compound [O-]C(=O)[C@@H](O)[C@H](O)C([O-])=O FEWJPZIEWOKRBE-LWMBPPNESA-L 0.000 claims description 4
- 125000001931 aliphatic group Chemical group 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 229910052700 potassium Inorganic materials 0.000 claims description 4
- 239000011591 potassium Substances 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
- NGPGDYLVALNKEG-OLXYHTOASA-N diammonium L-tartrate Chemical compound [NH4+].[NH4+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O NGPGDYLVALNKEG-OLXYHTOASA-N 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- KCIDZIIHRGYJAE-YGFYJFDDSA-L dipotassium;[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] phosphate Chemical compound [K+].[K+].OC[C@H]1O[C@H](OP([O-])([O-])=O)[C@H](O)[C@@H](O)[C@H]1O KCIDZIIHRGYJAE-YGFYJFDDSA-L 0.000 claims 1
- HELHAJAZNSDZJO-OTWIGTIJSA-L disodium;(2s,3s)-2,3-dihydroxybutanedioate Chemical group [Na+].[Na+].[O-]C(=O)[C@@H](O)[C@H](O)C([O-])=O HELHAJAZNSDZJO-OTWIGTIJSA-L 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 238000002955 isolation Methods 0.000 abstract 1
- 239000010815 organic waste Substances 0.000 abstract 1
- 150000003892 tartrate salts Chemical class 0.000 abstract 1
- 239000002002 slurry Substances 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- CAAMSDWKXXPUJR-UHFFFAOYSA-N 3,5-dihydro-4H-imidazol-4-one Chemical class O=C1CNC=N1 CAAMSDWKXXPUJR-UHFFFAOYSA-N 0.000 description 7
- 238000010586 diagram Methods 0.000 description 7
- 229960000443 hydrochloric acid Drugs 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000012065 filter cake Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 125000005219 aminonitrile group Chemical group 0.000 description 4
- 235000019524 disodium tartrate Nutrition 0.000 description 4
- 230000002363 herbicidal effect Effects 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 description 4
- 239000001433 sodium tartrate Substances 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000004009 herbicide Substances 0.000 description 3
- 229960003975 potassium Drugs 0.000 description 3
- 229940086065 potassium hydrogentartrate Drugs 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- NGPGDYLVALNKEG-UHFFFAOYSA-N azanium;azane;2,3,4-trihydroxy-4-oxobutanoate Chemical compound [NH4+].[NH4+].[O-]C(=O)C(O)C(O)C([O-])=O NGPGDYLVALNKEG-UHFFFAOYSA-N 0.000 description 2
- 235000016693 dipotassium tartrate Nutrition 0.000 description 2
- AVTYONGGKAJVTE-OLXYHTOASA-L potassium L-tartrate Chemical compound [K+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O AVTYONGGKAJVTE-OLXYHTOASA-L 0.000 description 2
- 239000001472 potassium tartrate Substances 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- YCPQUHCGFDFLSI-ZCFIWIBFSA-N (2r)-2-amino-2,3-dimethylbutanamide Chemical compound CC(C)[C@@](C)(N)C(N)=O YCPQUHCGFDFLSI-ZCFIWIBFSA-N 0.000 description 1
- CAOHBROWLMCZRP-ZCFIWIBFSA-N (2s)-2-amino-2,3-dimethylbutanenitrile Chemical compound CC(C)[C@](C)(N)C#N CAOHBROWLMCZRP-ZCFIWIBFSA-N 0.000 description 1
- GAVGQLYTJJGLTH-UHFFFAOYSA-N 2-amino-2-methylpentanenitrile Chemical compound CCCC(C)(N)C#N GAVGQLYTJJGLTH-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229960005069 calcium Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000002844 continuous effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- AUONNNVJUCSETH-UHFFFAOYSA-N icosanoyl icosanoate Chemical compound CCCCCCCCCCCCCCCCCCCC(=O)OC(=O)CCCCCCCCCCCCCCCCCCC AUONNNVJUCSETH-UHFFFAOYSA-N 0.000 description 1
- 229960004592 isopropanol Drugs 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229940091250 magnesium supplement Drugs 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 230000002311 subsequent effect Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/32—Separation; Purification; Stabilisation; Use of additives
- C07C253/34—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/02—Preparation of carboxylic acids or their salts, halides or anhydrides from salts of carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
- C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
-
- 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
- the present invention provides a process for the recovery of es - sentially enantiomerically pure D-tartaric acid from a waste stream containing D-tartrate salts which comprises acidifying said waste stream to a pH of about 2.5 to 4.5 to obtain a crystalline alkali metal hydrogen D-tartrate; and reacting said alkali metal hydrogen D-tartrate. with an acid, optionally in the presence of a solvent.
- the present invention also provides a process for the recycle of recovered D-tartaric acid in the continuous resolution of racemic 2-amino-2 , 3-dimethylbutyronitrile.
- Imidazolinone compounds for instance, those described in U.S. 4,188,487, U.S. 4,798,619 and U.S. 5,334,576 are highly potent, broad spectrum, environmentally benign, herbicidal agents. In general, the herbicidal activity of the R-isomer is approximately 1.8 times that of the racemic imidazolinone compound.
- Stereospe- cific processes to prepare chiral imidazolinone herbicidal agents, either directly or indirectly, from (R) 2-amino-2, 3 -dime- thylbutyronitrile are described in U.S. 4,683,324 and co-pending patent application Serial Number 09/304,401, filed an May 3, 1999.
- Said nitrile is prepared by a two-step resolution of racemic 2 -amino-2 , 3-dimethylbutyronitrile using D- (-) tartaric acid as the resolving agent.
- D-tartatic acid does not occur in abundance in nature, and methods for its production are limited.
- D- tartaric acid is commercially available, it is expensive and is only available in limited quantities.
- Imidazolinone compounds such as those described in U.S. 4,188,487, U.S. 4,798,619 and U.S. 5,334,576 are highly potent, broad spectrum, environmentally benign, herbicidal agents. Chiral imidazolinone compounds having the (R) configuration demonstrate an increase in herbicidal activity over the corresponding racemic mixture.
- the two-step resolution described comprises a first resolution step in which racemic 2 -amino-2 , 3-dimethylbutyroni- trile (II) in C ⁇ C -alkanol is treated with D-tartaric acid (I) to afford the D-tartrate salt of (R) 2-amino-2 , 4-dimethylbutyroni- trile (III), which crystallizes from solution. Because said ami- nonitrile partially decomposes in the process of this kinetic resolution, the methanol mother liquor contains varying amounts of ammonium D-tartrate (IV) , which is ordinarily discarded.
- This first resolution step is shown in Flow Diagram I wherein the C ⁇ -C -alkanol is methanol.
- This second resolution step is illustrated in flow diagram II Q wherein M is an alkali metal and the water immiscible solvent is toluene.
- D-tartaric acid is natural tartaric arid which occurs widely in nature, either as the free acid or in combination with potassium, calcium or magnesium
- D-tartaric acid does not occur widely in nature and is commercially available only in limited quantities. Further, existing methods for producing D-tartaric acid are limited.
- D-tartaric acid may be recovered in high yield and in essentially en- antiomerically pure form from the waste streams produced in the resolution of racemic 2-amino- 2, 3-dimethylbutyronitrile.
- the recovered D-tartaric acid may be recycled for use in the same resolution of said aminonitrile.
- the processes of this invention may be run repetitively, i.e., D-tartaric acid may be repeatedly recovered and recycled in a continu- ous resolution of racemic 2-amino-2 , 3-dimethylbutyronitrile, allowing for a sustainable resolution process.
- the di (alkali metal) D-tartrate or ammonium D-tartrate waste streams produced in the resolution of the above-said aminonitrile are acidified to a pH of about 2.5 to 4.5, preferably 3.0 to 4.0, most preferably about 3.0.
- the acidification is preferably conducted with hydro- chloric or sulfuric acid, to form the crystalline mono-basic hydrogen D-tartrate (VII) and said hydrogen D-tartrate is treated with at least one molar equivalent of an acid, optionally in the presence of a solvent, preferably an aliphatic alkanol, more pre- > ferably methanol or ethanol, to give essentially enantiomerically pure D-tartaric acid (I).
- a solvent preferably an aliphatic alkanol, more pre- > ferably methanol or ethanol
- the recovered D-tartaric acid (I) may then be utilized directly in the first resolution step by adding the recovered D-tartaric acid to a solution of racemic 2 -amino-2, 4-dimethylbutyronitrile in a water-immiscible solvent, such as toluene, to yield the corresponding D-tartrate salt (III) as shown hereinabove in flow diagram I .
- Acids suitable for use in the process of the invention include mineral acids such as hydrogen halides, sulfuric acid, phosphoric acid, or the like, preferably hydrochloric acid or sulfuric acid.
- Solvents suitable for use in the inventive process include polar solvents, preferably water miscible.
- Preferable solvents include aliphatic alkanols such as methanol, ethanol, propanol, isopropa- nol, or the like, preferably methanol or ethanol, more preferably ethanol .
- Alkali metals include sodium, potassium, or lithium, preferably sodium or postassium.
- reaction temperatures for the inventive process are directly related to reaction rate, that is increased reaction temperature leads to increased, reaction rate.
- exces- sively high reaction temperatures are to be avoided.
- Suitable reaction temperatures may be about 0°C to 50°C, preferably about 5°C to 35°C, more preferably about 10°C to 30°C.
- waste streams from a 2-step resolution of racemic 2-amino-2 , 3-dimethylbutyronitrile, combined or individually, are acidified to a pH of about 3 to form crystalline alkali metal hydrogen D-tartrate and said hydrogen D-tartrate is reacted with at least one molar equivalent of acid, preferably hydrochloric acid or sulfuric acid, optionally in the presence of a sol- vent, preferably an aliphatic alkanol, more preferably methanol or ethanol, to give the desired essentially enantiomerically pure D-tartaric acid.
- acid preferably hydrochloric acid or sulfuric acid
- the crystalline alkali metal hydrogen D-tartrate may be isolated using conventional means such as filtration or, alternatively, may be carried on in the inven- tive process as is or as a concentrated slurry.
- the recovered D-tartaric acid may be isolated using conventional techniques or recycled as is or as a concentrated slurry.
- HPLC designates high performance liquid chromatography. Unless otherwise indicated, all parts are parts by weight.
- a mixture of aqueous disodium tartrate waste produced as described in Example 1 (438.5 g, 14.5 wt% D-tartaric acid) and a methanolic mother liqucr waste slurry of ammonium tartrate (278 g, 2.6 wt% D-tartaric acid) produced as described in U.S. 4,683,324 is acidified to a pH of about 3 with concentrated hydrochloric acid over a 30 minute period at room temperature, stirred for 25 minutes and filtered. The filtercake is washed with methanol and dried under reduced pressure to afford 73.7 g (92% recovery) of D-sodium hydrogen tartrate as an off-white solid, in >99% purity and 100% optical purity, as determined by HPLC analysis.
- a slurry of recovered D-sodium hydrogen tartrate (20.6 g, 0.119 mol) in methanol is treated with concentrated sulfuric acid (6.1 g, 0.059 mol) at room temperature, stirred for one hour and filtered to remove inorganic salts. A portion of the filtrate is concentrated under reduced pressure to give a solution of recovered D-tartaric acid (13.6 g, 0.090 mol, 82%) in methanol. This solution is treated with a solution of racemic 2-amino-2, 3-dimethylbutyronitrile (12.4 g, 0.11 mol) in toluene, stirred for 16 hours and filtered.
- Aqueous dipotassium tartrate waste (137.0 g, 14.7 wt% D-tartaric acid) is acidified to a pH of about 3 with concentrated hydrochloric acid over a 30 minute period at 13-28°C, stirred for about 15 minutes and filtered.
- the filtercake is washed with methanol and dried under reduced pressure to afford 24.8 g (98% recovery) of D-potassium hydrogen tartrate, in >99% purity, as determined by HPLC analysis.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
There is provided a process for the recovery of essentially enantiomerically pure D-tartanic acid from aqueous and organic waste streams generated in the resolution of racemic 2-amino-2,3-dimethylbutyronitrile via the formation and isolation of a crystalline monobasic tartrate salt. The recovered optically pure D-tartaric acid may be efficiently recycled to provide a sustainable resolution of racemic 2-amino-2,3-dimethylbuty-ronitrile.
Description
PROCESS FOR THE RECOVERY AND RECYCLE OF D-TARTARIC ACID
The present invention provides a process for the recovery of es - sentially enantiomerically pure D-tartaric acid from a waste stream containing D-tartrate salts which comprises acidifying said waste stream to a pH of about 2.5 to 4.5 to obtain a crystalline alkali metal hydrogen D-tartrate; and reacting said alkali metal hydrogen D-tartrate. with an acid, optionally in the presence of a solvent.
The present invention also provides a process for the recycle of recovered D-tartaric acid in the continuous resolution of racemic 2-amino-2 , 3-dimethylbutyronitrile.
Imidazolinone compounds, for instance, those described in U.S. 4,188,487, U.S. 4,798,619 and U.S. 5,334,576 are highly potent, broad spectrum, environmentally benign, herbicidal agents. In general, the herbicidal activity of the R-isomer is approximately 1.8 times that of the racemic imidazolinone compound. Stereospe- cific processes to prepare chiral imidazolinone herbicidal agents, either directly or indirectly, from (R) 2-amino-2, 3 -dime- thylbutyronitrile are described in U.S. 4,683,324 and co-pending patent application Serial Number 09/304,401, filed an May 3, 1999.
Said nitrile is prepared by a two-step resolution of racemic 2 -amino-2 , 3-dimethylbutyronitrile using D- (-) tartaric acid as the resolving agent. D-tartatic acid does not occur in abundance in nature, and methods for its production are limited. Although D- tartaric acid is commercially available, it is expensive and is only available in limited quantities.
Therefore, it is an object of the present invention to provide a process for the recovery of D-tartaric acid from the two-step resolution of racemic 2-amino-2 , 3 -dimethylbutyronitrile.
It is another object of this invention to provide a process for the recycle of said recovered D-tartaric acid in the resolution process.
It is a feature of this invention that the processes provided thereby may be used for repeated recovery and reuse of D-tartaric acid in said two-step resolution .
Imidazolinone compounds such as those described in U.S. 4,188,487, U.S. 4,798,619 and U.S. 5,334,576 are highly potent, broad spectrum, environmentally benign, herbicidal agents. Chiral imidazolinone compounds having the (R) configuration demonstrate an increase in herbicidal activity over the corresponding racemic mixture. The preparation of said chiral compounds by the resolution of racemic 2-amino-2 , 3-dimethylbutyronitrile, hydrolysis of the resultant (R) 2-amino-2, 3-dimethylbutyronitrile to the corre¬ sponding (R) 2-amino-2 , 3 -dimethylbutyramide intermediate, and sub- sequent elaboration of this intermediate to the (R) imidazolinone herbicidal product is described in U.S. 4,683,324. The preparation of chiral imidazolinone compounds having substantially com¬ plete retention of enantiomeric purity directly from the (R)ami- nonitrile starting material to the final chiral imidazolinone herbicidal product is described in co-pending patent application Serial Number 09/304,401, filed an May 3, 1999.
In general, the two-step resolution described comprises a first resolution step in which racemic 2 -amino-2 , 3-dimethylbutyroni- trile (II) in Cι~C -alkanol is treated with D-tartaric acid (I) to afford the D-tartrate salt of (R) 2-amino-2 , 4-dimethylbutyroni- trile (III), which crystallizes from solution. Because said ami- nonitrile partially decomposes in the process of this kinetic resolution, the methanol mother liquor contains varying amounts of ammonium D-tartrate (IV) , which is ordinarily discarded. This first resolution step is shown in Flow Diagram I wherein the Cι-C -alkanol is methanol.
FLOW DIAGRAM I
(IV) 0
In the second resolution step, (R) 2-amino-2, 3 -dimethylbutyroni- trile (VI) is liberated from its D-tartrate Salt (III) by treatment with an alkali metal hydroxide in the presence of a minimum amount of water and a water-immiscible solvent, such as toluene. 5 This second resolution step yields an aqueous phase containing a full equivalent of the di (alkali metal) salt of D-tartaric acid (V) , which is also ordinarily discarded.
This second resolution step is illustrated in flow diagram II Q wherein M is an alkali metal and the water immiscible solvent is toluene.
5
FLOW DIAGRAM II
H20, MOH Toluene
Thus both resolution steps give rise to waste streams containing D-tartrate salts.
Although L-tartaric acid is natural tartaric arid which occurs widely in nature, either as the free acid or in combination with potassium, calcium or magnesium, D-tartaric acid does not occur widely in nature and is commercially available only in limited quantities. Further, existing methods for producing D-tartaric acid are limited. Surprisingly, it has now been found that D-tartaric acid may be recovered in high yield and in essentially en- antiomerically pure form from the waste streams produced in the resolution of racemic 2-amino- 2, 3-dimethylbutyronitrile. Advantageously, the recovered D-tartaric acid may be recycled for use in the same resolution of said aminonitrile. Beneficially, the processes of this invention may be run repetitively, i.e., D-tartaric acid may be repeatedly recovered and recycled in a continu- ous resolution of racemic 2-amino-2 , 3-dimethylbutyronitrile, allowing for a sustainable resolution process.
In accordance with the process of the invention the di (alkali metal) D-tartrate or ammonium D-tartrate waste streams produced in the resolution of the above-said aminonitrile are acidified to a pH of about 2.5 to 4.5, preferably 3.0 to 4.0, most preferably about 3.0. The acidification is preferably conducted with hydro-
chloric or sulfuric acid, to form the crystalline mono-basic hydrogen D-tartrate (VII) and said hydrogen D-tartrate is treated with at least one molar equivalent of an acid, optionally in the presence of a solvent, preferably an aliphatic alkanol, more pre- > ferably methanol or ethanol, to give essentially enantiomerically pure D-tartaric acid (I). The process of the invention is illustrated in flow diagram III wherein M is an alkali metal.
Flow Diagram III
2S,3R 2S,3R
(V) (VII)
H+
' 1
2S,3R
(I)
The recovered D-tartaric acid (I) may then be utilized directly in the first resolution step by adding the recovered D-tartaric acid to a solution of racemic 2 -amino-2, 4-dimethylbutyronitrile in a water-immiscible solvent, such as toluene, to yield the corresponding D-tartrate salt (III) as shown hereinabove in flow diagram I .
It is also intended that the processes of this invention embrace the recovery and recycle of L-tartaric acid in a resolution of racemic 2-amino-2, 3-dimethylbutyronitrile to produce (S) 2-amino-2, 3-dimethylbutyronitrile, such as that described in U.S. 4,683,324.
Acids suitable for use in the process of the invention include mineral acids such as hydrogen halides, sulfuric acid, phosphoric acid, or the like, preferably hydrochloric acid or sulfuric acid.
Solvents suitable for use in the inventive process include polar solvents, preferably water miscible. Preferable solvents include aliphatic alkanols such as methanol, ethanol, propanol, isopropa-
nol, or the like, preferably methanol or ethanol, more preferably ethanol .
Alkali metals include sodium, potassium, or lithium, preferably sodium or postassium.
In general, reaction temperatures for the inventive process are directly related to reaction rate, that is increased reaction temperature leads to increased, reaction rate. However, exces- sively high reaction temperatures are to be avoided. Suitable reaction temperatures may be about 0°C to 50°C, preferably about 5°C to 35°C, more preferably about 10°C to 30°C.
In actual practice, waste streams from a 2-step resolution of racemic 2-amino-2 , 3-dimethylbutyronitrile, combined or individually, are acidified to a pH of about 3 to form crystalline alkali metal hydrogen D-tartrate and said hydrogen D-tartrate is reacted with at least one molar equivalent of acid, preferably hydrochloric acid or sulfuric acid, optionally in the presence of a sol- vent, preferably an aliphatic alkanol, more preferably methanol or ethanol, to give the desired essentially enantiomerically pure D-tartaric acid. Advantageously, the crystalline alkali metal hydrogen D-tartrate may be isolated using conventional means such as filtration or, alternatively, may be carried on in the inven- tive process as is or as a concentrated slurry. Similarly, the recovered D-tartaric acid may be isolated using conventional techniques or recycled as is or as a concentrated slurry.
In order to facilitate a further understanding of the invention, the following examples are presented primarily for the purpose of illustrating certain more specific details thereof. The invention is not to be deemed limited thereby except as defined in the claims. HPLC designates high performance liquid chromatography. Unless otherwise indicated, all parts are parts by weight.
EXAMPLE 1
Recovery of D-sodium hydrogen tartrate from aqueous disodium tartrate waste:
HC1
A mixture of (R) -2-amino-2 , 3-dimethylbutyronitrile (2S,3S)-tar- taric acid salt (89.9 g, 0.34 mmole), toluene, ice and 50% sodium hydroxide (68.5 g, 0.85 mmol) is shaken until no solid particles are observed. The phases are separated and the aqueous disodium tartrate waste produced (343.3 g, 15 wt% D-tartaric acid) is acidified to a pH of about 3 with concentrated hydrochloric acid over a 30 minute period at 8°C to 13°C, stirred for 15 minutes and filtered. The filtercake is washed with methanol and dried under reduced pressure to afford 53.2 g (91% recovery) of D-sodium hydrogen tartrate as an off-white solid in >99% purity and 100% optical purity as determined by HPLC analysis.
Using essentially the same procedure and employing concentrated sulfuric acid in place of concentrated hydrochloric acid, 27.9 g (77% recovery) D-sodium hydrogen tartrate are obtained as an off- white solid, in >99% purity and 100% optical purity, as determined by HPLC analysis.
EXAMPLE 2
Recovery of D-sodium hydrogen tartrate from combined aqueous disodium tartrate and methanolic ammonium tartrate waste:
EXAMPLE 3
Preparation of (R) -2-amino-2 , 3-dimethylbutyronitrile (2S,3S)-tar- trate from recovered D-sodium hydrogen tartrate:
(Racemic)
A slurry of recovered D-sodium hydrogen tartrate (20.6 g, 0.119 mol) in methanol is treated with concentrated sulfuric acid (6.1 g, 0.059 mol) at room temperature, stirred for one hour and filtered to remove inorganic salts. A portion of the filtrate is concentrated under reduced pressure to give a solution of recovered D-tartaric acid (13.6 g, 0.090 mol, 82%) in methanol. This solution is treated with a solution of racemic 2-amino-2, 3-dimethylbutyronitrile (12.4 g, 0.11 mol) in toluene, stirred for 16 hours and filtered. The filtercake is washed with methanol and dried to afford 22.3 g (61% yield) of (R) -2-amino-2, 3-dimethylbutyronitrile (2S, 3S) -tartrate, in a 95/5 R/S isomer ratio, as determined by HPLC analysis.
EXAMPLE 4
Preparation of crystalline D-tartaric acid from recovered
D-sodium hydrogen tartrate in ethanol:
( 2S , 3R) A slurry of recovered D-sodium hydrogen tartrate (50.5 g, 0.293 mol) in ethanol is treated with concentrated sulfuric acid (15.0 g, 0.147 mol) at room temperature, stirred for 45 minutes
and filtered to remove inorganic salts. The filtrate is concentrated under reduced pressure to afford a concentrated slurry of D-tartaric acid in ethanol. The slurry is diluted with toluene and filtered. The filtercake is washed with toluene and dried to afford 37.3 g (83% yield) of D-tartaric acid as a crystalline solid, in 97.7% purity and 100% optical purity, as determined by HPLC analysis.
EXAMPLE 5 Recovery of D-potassium hvdrogen tartrate from aqueous dipotassium tartrate waste:
(2S,3R)
Aqueous dipotassium tartrate waste (137.0 g, 14.7 wt% D-tartaric acid) is acidified to a pH of about 3 with concentrated hydrochloric acid over a 30 minute period at 13-28°C, stirred for about 15 minutes and filtered. The filtercake is washed with methanol and dried under reduced pressure to afford 24.8 g (98% recovery) of D-potassium hydrogen tartrate, in >99% purity, as determined by HPLC analysis.
EXAMPLE 6
Preparation of crystalline D-tartaric acid from recovered D-potassium hydrogen tartrate in ethanol:
HO
(2S,3R) (D)
A slurry of recovered D-potassium hydrogen tartrate (22.1 g,
0.117 mol) in ethanol (148 g) is treated with concentrated sulfuric acid (6.0 g, 0.0588 mol) at room temperature, stirred for 45 minutes and filtered to remove inorganic salts. The filtrate is concentrated under reduced pressure to a viscous slurry. The slurry is diluted with acetonitrile and filtered. The filtercake is washed with acetonitrile and dried to afford 4.7 g (25% recovery) of crystalline D-tartaric acid, in 92.3% purity, as determined by HPLC analysis.
Claims
1. A process for the recovery of essentially enantiomerically 5 pure D-tartaric acid from a waste stream containing D-tartrate salts which comprises acidifying said waste stream to a pH of about 2.5 to 4.5 to obtain a crystalline alkali metal hydrogen D-tartrate; and reacting said alkali metal hydrogen D-tartrate with at least one molar equivalent of an acid, op-
10 tionally in the presence of a solvent.
2. The process according to Claim 1 wherein the alkali metal is sodium or potassium.
15 3. The process according to Claim 1 wherein the acid is a mineral acid.
4. The process according to Claim 3 wherein the acid is hydrochloric acid or sulfuric acid.
20
5. The process according to Claim 1 wherein the solvent is methanol or ethanol .
6. The process according to Claim 4 wherein the solvent is 25 ethanol.
7. The process according to Claim 1 wherein the D-tartrate salt is disodium D-tartrate, dipotassium D-tartrate, ammonium D- tartrate or a mixture thereof .
30
8. The process according to Claim 1 wherein the alkali metal hydrogen D-tartrate is reacted with one molar equivalent of acid.
35 9. The process according to Claim 1 wherein the pH is about 3.0 to 4.0.
10. The process according to Claim 9 wherein the pH is about 3.0.
40 11. A process for the continuous resolution of racemic 2 -amino-2, 3-dimethylbutyronitrile having D-tartaric acid as resolving agent which comprises the following steps: a) reacting racemic 2-amino-2 , 3-dimethylbutyronitrile with D-tartaric acid in the presence of Cχ-C4-alkanol to give the crys- 45 talline D-tartrate salt of (R) -2-amino-2, 3 -dimethylbutyro- nitrile and a first waste stream; b) reacting said D-tartrate salt with an alkali metal hydroxide in the presence of water and a water-immiscible solvent to give (R) -2-amino-2, 3-dimethylbutyronitrile and a second waste stream; 5 c) acidifying said first and second waste streams to a pH of about 2.5 to 4.5 to form a crystalline alkali metal hydrogen D-tartrate salt; d) reacting said hydrogen D-tartrate salt with at least one molar equivalent of an acid, optionally in the presence of a solvent 10 to give essentially enantiomerically pure D-tartaric acid; and e) reacting said D-tartaric acid according to steps a) through d) .
12. The process according to claim 11 wherein the pH in step c is about 15 3.0 to 4.0.
13. The process according to claim 11 wherein the water-immiscible solvent in step b is toluene.
20 14. The process according to claim 11 wherein the solvent in step d is an aliphatic alkanol.
15. The process according to claim 11 wherein the Cχ-C4- alkanol is methanol . 25
30
35
40
45
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU31606/01A AU3160601A (en) | 1999-12-28 | 2000-12-19 | Process for the recovery and recycle of d-tartaric acid |
| EP00991215A EP1242353A1 (en) | 1999-12-28 | 2000-12-19 | Process for the recovery and recycle of d-tartaric acid |
| IL15015500A IL150155A0 (en) | 1999-12-28 | 2000-12-19 | Process for the recovery and recycle of d-tartaric acid |
| BR0016803-3A BR0016803A (en) | 1999-12-28 | 2000-12-19 | Processes for the recovery of essentially enanciometrically pure d-tartaric acid from a tailing stream containing d-tartrate salts, and for the continuous decomposition of racemic 2-amino-2-3-dimethylbutyronitrile with d-tartaric acid as the decomposition agent |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17337299P | 1999-12-28 | 1999-12-28 | |
| US60/173,372 | 1999-12-28 | ||
| US47364899A | 1999-12-29 | 1999-12-29 | |
| US09/473,648 | 1999-12-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2001047856A1 true WO2001047856A1 (en) | 2001-07-05 |
Family
ID=26869068
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2000/012946 WO2001047856A1 (en) | 1999-12-28 | 2000-12-19 | Process for the recovery and recycle of d-tartaric acid |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP1242353A1 (en) |
| CN (1) | CN1414939A (en) |
| AR (1) | AR027145A1 (en) |
| AU (1) | AU3160601A (en) |
| BR (1) | BR0016803A (en) |
| IL (1) | IL150155A0 (en) |
| WO (1) | WO2001047856A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MD4504C1 (en) * | 2016-04-13 | 2018-03-31 | Общественное Учреждение "Научно-Практический Институт Садоводства И Пищевых Технологий" | Process for producing tartaric acid from calcium tartrate obtained from wine-making waste |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101643409B (en) * | 2009-08-31 | 2013-04-24 | 厦门世达膜科技有限公司 | Production method for converting sodium tartrate into tartaric acid |
| CN101782548B (en) * | 2009-12-03 | 2013-07-24 | 浙江工业大学 | New method for separating 2,4-dichlorprop enantiomer by capillary electrophoresis |
| CN101906032A (en) * | 2010-07-14 | 2010-12-08 | 华东理工大学 | Method for recovering and recycling L-(+)-tartaric acid |
| CN102503810B (en) * | 2011-11-02 | 2014-05-21 | 浙江科技学院 | Method for recovering and recycling L-tartaric acid |
| CN103834964A (en) * | 2013-12-31 | 2014-06-04 | 浙江工业大学 | Separation method for 2-methyl-4-chloropentyloxy propionic acid enantiomer through capillary electrophoresis |
| CN105152911B (en) * | 2015-08-17 | 2017-05-31 | 浙江邦成化工有限公司 | A kind of recovery method of tartaric acid |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE264005C (en) * | ||||
| US4683324A (en) * | 1982-05-25 | 1987-07-28 | American Cyanamid Company | Process for the resolution of certain racemic amino nitriles |
| DE19819884A1 (en) * | 1998-05-04 | 1999-11-11 | Metallgesellschaft Ag | Recovery of tartaric acid from material containing K hydrogen tartrate (KHT), e.g. wine yeast or tartar |
-
2000
- 2000-12-19 CN CN00817998.0A patent/CN1414939A/en active Pending
- 2000-12-19 EP EP00991215A patent/EP1242353A1/en not_active Withdrawn
- 2000-12-19 AU AU31606/01A patent/AU3160601A/en not_active Abandoned
- 2000-12-19 IL IL15015500A patent/IL150155A0/en unknown
- 2000-12-19 BR BR0016803-3A patent/BR0016803A/en not_active Application Discontinuation
- 2000-12-19 WO PCT/EP2000/012946 patent/WO2001047856A1/en not_active Application Discontinuation
- 2000-12-28 AR ARP000107007A patent/AR027145A1/en unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE264005C (en) * | ||||
| US4683324A (en) * | 1982-05-25 | 1987-07-28 | American Cyanamid Company | Process for the resolution of certain racemic amino nitriles |
| DE19819884A1 (en) * | 1998-05-04 | 1999-11-11 | Metallgesellschaft Ag | Recovery of tartaric acid from material containing K hydrogen tartrate (KHT), e.g. wine yeast or tartar |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MD4504C1 (en) * | 2016-04-13 | 2018-03-31 | Общественное Учреждение "Научно-Практический Институт Садоводства И Пищевых Технологий" | Process for producing tartaric acid from calcium tartrate obtained from wine-making waste |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1414939A (en) | 2003-04-30 |
| AU3160601A (en) | 2001-07-09 |
| EP1242353A1 (en) | 2002-09-25 |
| BR0016803A (en) | 2002-09-10 |
| IL150155A0 (en) | 2002-12-01 |
| AR027145A1 (en) | 2003-03-12 |
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