CN1300090C - Process for preparing aryl acetic acid - Google Patents
Process for preparing aryl acetic acid Download PDFInfo
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- CN1300090C CN1300090C CNB2005100491663A CN200510049166A CN1300090C CN 1300090 C CN1300090 C CN 1300090C CN B2005100491663 A CNB2005100491663 A CN B2005100491663A CN 200510049166 A CN200510049166 A CN 200510049166A CN 1300090 C CN1300090 C CN 1300090C
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- pentanoyl
- news
- new ideas
- glucosyl group
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- -1 aryl acetic acid Chemical compound 0.000 title claims abstract description 46
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 238000004519 manufacturing process Methods 0.000 title description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 55
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims abstract description 54
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 30
- 238000000034 method Methods 0.000 claims abstract description 24
- 238000006243 chemical reaction Methods 0.000 claims abstract description 20
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229910052723 transition metal Inorganic materials 0.000 claims abstract description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 10
- 150000003624 transition metals Chemical class 0.000 claims abstract description 9
- 239000002841 Lewis acid Substances 0.000 claims abstract description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 6
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000005935 nucleophilic addition reaction Methods 0.000 claims abstract description 5
- 125000003118 aryl group Chemical group 0.000 claims abstract description 3
- 150000007517 lewis acids Chemical class 0.000 claims abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 92
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 51
- 239000000243 solution Substances 0.000 claims description 50
- 239000002253 acid Substances 0.000 claims description 39
- 150000007513 acids Chemical class 0.000 claims description 25
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 claims description 22
- 238000002360 preparation method Methods 0.000 claims description 19
- 239000002904 solvent Substances 0.000 claims description 19
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims description 17
- 238000001035 drying Methods 0.000 claims description 17
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical group Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 16
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 229910000039 hydrogen halide Inorganic materials 0.000 claims description 10
- 239000012433 hydrogen halide Substances 0.000 claims description 10
- 239000012044 organic layer Substances 0.000 claims description 10
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 8
- 230000002378 acidificating effect Effects 0.000 claims description 7
- 238000006460 hydrolysis reaction Methods 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 7
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 6
- 238000007171 acid catalysis Methods 0.000 claims description 6
- 238000001953 recrystallisation Methods 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 6
- 238000010792 warming Methods 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 3
- 229960001701 chloroform Drugs 0.000 claims description 3
- 238000009833 condensation Methods 0.000 claims description 3
- 230000005494 condensation Effects 0.000 claims description 3
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 2
- JMANVNJQNLATNU-UHFFFAOYSA-N glycolonitrile Natural products N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 claims description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 2
- 229910000043 hydrogen iodide Inorganic materials 0.000 claims description 2
- 239000011968 lewis acid catalyst Substances 0.000 claims description 2
- 239000000758 substrate Substances 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims 1
- 239000006227 byproduct Substances 0.000 abstract description 6
- 239000002994 raw material Substances 0.000 abstract description 6
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 abstract description 4
- 230000008901 benefit Effects 0.000 abstract description 3
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 2
- 239000012847 fine chemical Substances 0.000 abstract description 2
- 238000010586 diagram Methods 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 239000000796 flavoring agent Substances 0.000 abstract 1
- 235000019634 flavors Nutrition 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 150000002367 halogens Chemical class 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 abstract 1
- 239000000575 pesticide Substances 0.000 abstract 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 abstract 1
- 239000012043 crude product Substances 0.000 description 10
- 230000002194 synthesizing effect Effects 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 4
- TZRXHJWUDPFEEY-UHFFFAOYSA-N Pentaerythritol Tetranitrate Chemical compound [O-][N+](=O)OCC(CO[N+]([O-])=O)(CO[N+]([O-])=O)CO[N+]([O-])=O TZRXHJWUDPFEEY-UHFFFAOYSA-N 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- PRPINYUDVPFIRX-UHFFFAOYSA-N 1-naphthaleneacetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CC=CC2=C1 PRPINYUDVPFIRX-UHFFFAOYSA-N 0.000 description 2
- LSBDFXRDZJMBSC-UHFFFAOYSA-N 2-phenylacetamide Chemical compound NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- MNZMECMQTYGSOI-UHFFFAOYSA-N acetic acid;hydron;bromide Chemical compound Br.CC(O)=O MNZMECMQTYGSOI-UHFFFAOYSA-N 0.000 description 2
- 229940073608 benzyl chloride Drugs 0.000 description 2
- 230000006315 carbonylation Effects 0.000 description 2
- 238000005810 carbonylation reaction Methods 0.000 description 2
- 238000000151 deposition Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- ITIONVBQFUNVJV-UHFFFAOYSA-N Etomidoline Chemical compound C12=CC=CC=C2C(=O)N(CC)C1NC(C=C1)=CC=C1OCCN1CCCCC1 ITIONVBQFUNVJV-UHFFFAOYSA-N 0.000 description 1
- 229910000914 Mn alloy Inorganic materials 0.000 description 1
- AHIBWURJLGCHAY-UHFFFAOYSA-N [S].C1=CC=CC=C1 Chemical compound [S].C1=CC=CC=C1 AHIBWURJLGCHAY-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960004217 benzyl alcohol Drugs 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 230000021523 carboxylation Effects 0.000 description 1
- 238000006473 carboxylation reaction Methods 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 150000001868 cobalt Chemical class 0.000 description 1
- 150000001869 cobalt compounds Chemical class 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000007772 electrode material Substances 0.000 description 1
- 239000008151 electrolyte solution Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 229940087654 iron carbonyl Drugs 0.000 description 1
- DALUDRGQOYMVLD-UHFFFAOYSA-N iron manganese Chemical compound [Mn].[Fe] DALUDRGQOYMVLD-UHFFFAOYSA-N 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000010641 nitrile hydrolysis reaction Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 231100000004 severe toxicity Toxicity 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- 229940006198 sodium phenylacetate Drugs 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 239000003115 supporting electrolyte Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The present invention relates to a method for preparing aryl acetic acid which can be used as important fine chemical intermediates of medicines, pesticide, flavor, etc. The method of the present invention is characterized in that N-(2, 3, 4, 6-tetrapentanoyl glucosyl) aryl imine (disclosed in the formula II) is catalyzed by transition metals and the Lewis acid to carry out nucleophilic addition reaction with trimethylsilyl cyanide in tetrahydrofuran or acetonitrile or hydrochloric ether which contains 1 to 3 carbon atoms or alcohol which contains 3 to 4 carbon atoms to obtain N-(2, 3, 4, 6-tetrapentanoyl glucosyl))-alpha-amido aryl acetonitrile (disclosed in the formula III); the N-(2, 3, 4, 6-tetrapentanoyl glucosyl)-alpha-amido aryl acetonitrile is hydrolyzed in a halogen hydride acetic acid solution to obtain aryl acetic acid (disclosed in the formula IV). The method of the present invention has the advantages of low cost and easy acquisition of raw materials, low cost, simple and secure operation, high reaction yield, good implementation value and good social and economic benefit; sodium cyanide or hydrocyanic acid which is used as the raw material is not used, and side products can be effectively recycled. The reaction formula is disclosed in the diagram; in the formula II and the formula III, Piv=(CH3)3CCO; in the formula IV, Ar represents an aryl group.
Description
(1) technical field
The present invention relates to the preparation method of fine chemicals intermediate Arylacetic acids such as important medicine, agricultural chemicals, spices.
(2) background technology
In the prior art, the chemical synthesis process of relevant toluylic acid has:
One, the nitrile hydrolysis method prepares target compound:
The benzyl cyanide hydrolysis method has alkalescence and two kinds of sour water solutions, and benzyl cyanide is by the condensation and getting under necessarily medium and catalyzer of benzyl chloride and sodium cyanide, and benzyl cyanide hydrolysis generally adopts alkaline hydrolysis technology, reacts as follows:
Above-mentioned technology weak point has: raw material NaCN and intermediate product benzyl cyanide toxicity are very big, particularly can produce severe toxicity in the benzyl cyanide synthesis procedure and have malodorous material isocyanide benzyl, these material high volatilities, operating environment is caused severe contamination, contaminated wastewater is heavy, the processing costs height, the benzyl cyanide yield is not high, the production cost height.From long term growth trend, this method will be eliminated gradually.
Two, benzene, formaldehyde and reaction of carbon monoxide prepare target compound:
That this method is under high pressure reacted is dangerous, amount is difficult for industrialization for a short time, catalyzer is expensive and be difficult for reclaiming.
Three, phenylacetamide hydrolysis method (Virgo Luo Defa) preparation target compound:
The above-mentioned technology the first step need pressurize and have by product benzene sulfur alcohol to produce, and this by product foul smelling is seriously polluted.
Four, the phenylcarbinol legal system is equipped with target compound:
Under 150 ℃ of high pressure, react and got toluylic acid in 4～5 hours:
This catalysts manufacturing difficulty, cost an arm and a leg, reaction pressure height, dangerous big.
Five, benzyl chlorocarbonylation legal system is equipped with target compound:
This is reflected at catalyzer (organic palladium complex compound, rhodium complex, iron carbonyl, iron-manganese alloy, cobalt salt and carbonylic cobalt compound etc.) effect down, add suitable organic solvent, make benzyl chlorine in two-phase system, carry out carbonylation, under acidic conditions, the sodium phenylacetate acidifying become toluylic acid:
Technical requirements height in this technological process, need to use expensive catalyzer and the very tiny need of granules of catalyst meticulously operation in case catalyst deactivation or loss, catalyst separating difficulty, shortcoming such as recovery method is still immature, and the production difficulty is big.
Six, benzyl chloro-carbonic acid gas electrolytic process prepares target compound:
Electrolytic process preparing phenylacetic acid technology is to adopt sacrificial anode protection to realize electric carboxylation, and benzyl chloride is synthesized toluylic acid through electric carbonylation.As being example as anode, react as follows with Mg:
Total reaction:
Electrode materials and electrolytic solution are more expensive in this method, and current consumption is big, and the Separation and Recovery of solvent, supporting electrolyte and by product is utilized difficulty, and the cost height is difficult for industrialization.
(3) summary of the invention
For solving Arylacetic acids in the prior art especially preparation cost height, complex process, dangerous big, the deficiency that yield is low of toluylic acid, the invention provides the preparation method of the Arylacetic acids that a kind of cost is low, technology is reasonable, production safety is reliable, reaction yield is high.
For reaching goal of the invention the technical solution used in the present invention be:
A kind of preparation method of the Arylacetic acids as Formula I V, described method is with formula IIN-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group) aryl imine under the transition metal Louis acid catalysis at tetrahydrofuran (THF) or acetonitrile or contain the hydrochloric ether of 1～3 carbon atom or contain and carry out nucleophilic addition with the trimethyl silicane prussiate in the alcohol of 3～4 carbon atoms and obtain: formula III N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-the alpha-azyl aryl acetonitrile, N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-hydrolysis in the hydrogen halide acetic acid solution of alpha-azyl aryl acetonitrile obtains the described Arylacetic acids of formula IV; Reaction formula is as follows:
Among formula II, the III, Piv=(CH
3)
3CCO; Among formula II, III, the IV, Ar is an aryl.
With the toluylic acid is example, and described Arylacetic acids preparation method is as follows:
N-(2; 3; 4,6-"four news" (new ideas pentanoyl glucosyl group) phenyl imine under the transition metal Louis acid catalysis at tetrahydrofuran (THF) or acetonitrile or contain the hydrochloric ether of 1～3 carbon atom or contain and carry out nucleophilic addition with the trimethyl silicane prussiate in the alcohol of 3～4 carbon atoms and obtain N-(2,3; 4; 6-"four news" (new ideas pentanoyl glucosyl group)-and the alpha-amino group benzyl cyanide, N-(2,3; 4,6-"four news" (new ideas pentanoyl glucosyl group)-hydrolysis in the hydrogen halide acetic acid solution of alpha-amino group benzyl cyanide obtains described toluylic acid.
Described transition metal Lewis acid is one of following:
①SnCl
4 ②ZnCl
2 ③TiCl
4 ④ZnI
2 ⑤CuCl ⑥CuBr
⑦CuBr.S(CH
3)
2 ⑧CuCl
2 ⑨CuBr
2。
Described organic solvent is one of following:
1. 2. 3. 4. 5. acetonitrile of tetrahydrofuran (THF) of Virahol of trichloromethane of methylene dichloride.
The hydrogen halide mass content is 30～50% in the described hydrogen halide acetic acid solution, and described hydrogen halide is hydrogen bromide or hydrogen iodide.
Described transition metal Lewis acid is preferably 1: 1 with the ratio of trimethyl silicane prussiate amount of substance.
Concrete, described method is as follows:
～-20 ℃ (1)-40 under, in being dissolved with the lewis acidic dichloromethane solution of trimethyl silicane prussiate and transition metal, drips the dichloromethane solution that contains N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group) aryl imine;
(2) stir and to be warming up to room temperature and to react, reaction boils off solvent after finishing, residuum dissolves with methylene dichloride, washs after drying, evaporate to dryness again, and evaporate to dryness thing recrystallization in normal heptane obtains N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-the alpha-azyl aryl acetonitrile;
(3) N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-alpha-azyl aryl acetonitrile is dissolved in the dichloromethane solution, drips 45%HBr/HAc solution again, at room temperature kept 1～4 hour, filter, get described Arylacetic acids.
Further, described method is as follows:
～-20 ℃ (1)-40 under, in being dissolved with the lewis acidic dichloromethane solution of trimethyl silicane cyanogen compound and transition metal, drip and contain N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group) dichloromethane solution of aryl imine, described trimethyl silicane prussiate, lewis acid catalyst, N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group) ratio of aryl imine amount of substance is 1.25: 1.25: 1;
(2) stir and to be warming up to room temperature and to react, after reaction finishes, boil off solvent, residuum is dissolved in the methylene dichloride, after dichloromethane solution is used the hydrochloric acid, saturated sodium bicarbonate aqueous solution, water washing of 2N successively, use dried over mgso, evaporate to dryness again after the drying, evaporate to dryness thing again in normal heptane recrystallization just obtain N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-the alpha-azyl aryl acetonitrile;
(3) N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-alpha-azyl aryl acetonitrile is dissolved in the dichloromethane solution, drips 45%HBr/HAc solution again, at room temperature keep 1～4 hour after, filter, described Arylacetic acids.
Especially, when described Arylacetic acids was toluylic acid, the preparation method was as follows:
～-20 ℃ (1)-40 under, in being dissolved with trimethyl silicane prussiate and lewis acidic dichloromethane solution, drip and contain N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group) dichloromethane solution of phenyl imine, trimethyl silicane prussiate, Lewis acid, N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group) the phenyl imine mol ratio is 1.25: 1.25: 1;
(2) stir and to be warming up to room temperature and to react, reaction boils off solvent after finishing, and residuum is dissolved in CH
2Cl
2In, organic layer is used 2N hydrochloric acid, saturated sodium bicarbonate aqueous solution and water washing successively, uses MgSO then
4Drying, evaporate to dryness again after the drying, the evaporate to dryness thing is recrystallization in normal heptane again;
(3) N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-alpha-amino group benzyl cyanide is dissolved in the dichloromethane solution, drips 45%HBr/HAc solution again, at room temperature kept 1～4 hour, filter, get the toluylic acid solid.
Described formula II N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group) aryl imine is generally by formula I N-2, and 3,4,6-"four news" (new ideas pentanoyl glucosyl group amine is substrate, makes through acid catalysis and aldehyde condensation, reaction formula is as follows:
The preparation method's of Arylacetic acids of the present invention beneficial effect is mainly reflected in: (1) raw material is cheap and easy to get, and cost is low; (2) avoid using raw material sodium cyanide or prussic acid, safety simple to operate, reaction yield height; (3) by product can be recycled effectively, has bigger implementary value and economic results in society.
(4) embodiment
The present invention is described further below in conjunction with specific embodiment:
Synthesizing of embodiment 1:N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-alpha-amino group benzyl cyanide
In the time of-40 ℃～-20 ℃; in methylene dichloride (20mL) solution that is dissolved with 3.96 gram trimethyl silicane nitrine prussiates (37.5mmol) and CuBr (37.5mmol), slowly drip 1mL and contain (30mmol) N-(2; 3,4,6-"four news" (new ideas pentanoyl glucosyl group) dichloromethane solution of phenyl imine; drip the back under stirring; solution slowly is warmed up to-20 ℃, is reflected at-20 ℃ and carries out and monitor with TLC, after reaction finishes; boil off solvent, then remaining resistates is dissolved in 400mLCH
2Cl
2In, organic layer is used 2N HCl (100mL), saturated NaHCO successively
3The washing of (200mL * 3) and water (200mL), organic layer MgSO
4Drying boils off solvent and gets crude product 16.3 grams after the drying, yield is 86%.
Synthesizing of embodiment 2:N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-alpha-amino group benzyl cyanide
When-20 ℃～O ℃; in methylene dichloride (20mL) solution that is dissolved with 3.96 gram trimethyl silicane nitrine prussiates (37.5mmol) and CuBr (37.5mmol), slowly drip 1mL and contain 30mmolN-(2; 3,4,6-"four news" (new ideas pentanoyl glucosyl group) dichloromethane solution of phenyl imine; drip the back under stirring; solution slowly is warmed up to O ℃, is reflected at O ℃ and carries out and monitor with TLC, after reaction finishes; boil off solvent, then remaining resistates is dissolved in 400mL CH
2Cl
2In, organic layer is used 2N HCl (100mL), saturated NaHCO successively
3The washing of (200mL * 3) and water (200mL), organic layer MgSO
4Drying boils off solvent and gets crude product 16.8 grams after the drying, yield is 89%.
Synthesizing of embodiment 3:N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-alpha-amino group benzyl cyanide
In the time of O ℃～25 ℃; in methylene dichloride (20mL) solution that is dissolved with 3.96 gram trimethyl silicane nitrine prussiates (37.5mmol) and CuBr (37.5mmol), slowly drip 1mL and contain 30mmolN-(2; 3,4,6-"four news" (new ideas pentanoyl glucosyl group) dichloromethane solution of benzene imines; drip the back under stirring; solution slowly is warmed up to 25 ℃, is reflected at 25 ℃ and carries out and monitor with TLC, after reaction finishes; boil off solvent, then remaining resistates is dissolved in 400mL CH
2Cl
2In, organic layer is used 2N HCl (100mL), saturated NaHCO successively
3The washing of (200mL * 3) and water (200mL), organic layer MgSO
4Drying boils off solvent after the drying, boil off solvent after the drying and get crude product 17.0 grams, and yield is 90%.
Synthesizing of embodiment 4:N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-alpha-amino group benzyl cyanide
Catalyst levels be (75mmol) other with embodiment 3, crude product 17.20 gram, yield is 91%.
Synthesizing of embodiment 5:N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-alpha-amino group benzyl cyanide
Solvent changes tetrahydrofuran (THF) into, and other gets crude product 16.6 grams with embodiment 3, and yield is 88%.
The synthesis reaction solvent of embodiment 6:N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-alpha-amino group benzyl cyanide changes trichloromethane into, and other gets crude product 16.07 grams with embodiment 3, and yield is 85%.
Synthesizing of embodiment 7:N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-alpha-amino group benzyl cyanide
Catalyzer SnCl
4, other gets crude product 13.4 grams with embodiment 3, and yield is 71%.
Synthesizing of embodiment 8:N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-alpha-amino group benzyl cyanide
Catalyzer TiCl
4, solvent changes acetonitrile into, and other gets crude product 11.34 grams with embodiment 3, and yield is 60%.
Synthesizing of embodiment 9:N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-alpha-amino group benzyl cyanide
Catalyzer ZnI
2, solvent changes Virahol into, and other gets crude product 11.4 grams with embodiment 3, and yield is 45%.
Synthesizing of embodiment 10:N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-α-An Jinai acetonitrile
When room temperature; in methylene dichloride (20mL) solution that is dissolved with 3.96 gram trimethyl silicane nitrine prussiates (37.5mmol) and CuBr (37.5mmol), slowly drip 1mL and contain (30mmol) N-(2; 3,4,6-"four news" (new ideas pentanoyl glucosyl group) dichloromethane solution of naphthyl imine; drip the back under stirring; solution slowly is warmed up to 25 ℃, is reflected at 25 ℃ and carries out and monitor with TLC, after reaction finishes; boil off solvent, then remaining resistates is dissolved in 400mL CH
2Cl
2In, organic layer is used 2N HCl (100mL), saturated NaHCO successively
3The washing of (200mL * 3) and water (200mL), organic layer MgSO
4Drying boils off solvent and gets crude product 18.56 grams after the drying, yield is 91%.
Embodiment 11: toluylic acid is synthetic
At room temperature; to being dissolved with embodiment 3 gained N-(2; 3; 4; 6-"four news" (new ideas pentanoyl glucosyl group)-methylene dichloride (200mL) solution of alpha-amino group benzyl cyanide (13.25g) in slowly hydrogen bromide acetic acid solution and the 1mL water of Dropwise 5 .5mL45%, drip the back under stirring, will have solid precipitation to generate; filtering-depositing just gets toluylic acid solid 2.59 grams, and yield is 91%.
Embodiment 12: naphthylacetic acid synthetic
At room temperature; to being dissolved with embodiment 10 gained N-(2; 3; 4; 6-"four news" (new ideas pentanoyl glucosyl group)-methylene dichloride (200mL) solution of α-naphthalene acetonitrile (14.3g) in slowly hydrogen bromide acetic acid solution and the 1mL water of Dropwise 5 .5mL45%, drip the back under stirring, will have solid precipitation to generate; filtering-depositing just gets naphthylacetic acid solid 3.5g, and yield is 90%.
The present invention and existing chemical synthesis process relatively, advantage such as have raw material safety cheap and easy to get, simple to operate, reaction time is short, reaction yield is high, good product quality and by product can be recycled effectively is a method that is suitable for suitability for industrialized production.
Claims (10)
1. preparation method as the Arylacetic acids of Formula I V, it is characterized in that described method is with formula II N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group) aryl imine carries out nucleophilic addition with the trimethyl silicane prussiate and obtains in organic solvent under the transition metal Louis acid catalysis: formula III N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-the alpha-azyl aryl acetonitrile, N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-hydrolysis in the hydrogen halide acetic acid solution of alpha-azyl aryl acetonitrile obtains the described Arylacetic acids of formula IV; Described organic solvent is tetrahydrofuran (THF) or acetonitrile or contains the hydrochloric ether of 1～3 carbon atom or contain the alcohol of 3～4 carbon atoms;
Among formula II, the III, Piv=(CH
3)
3CCO; Among formula II, III, the IV, Ar is an aryl.
2. the preparation method of Arylacetic acids as claimed in claim 1 is characterized in that described Arylacetic acids is a toluylic acid, and described method is as follows:
N-(2; 3; 4,6-"four news" (new ideas pentanoyl glucosyl group) the benzene imines under the transition metal Louis acid catalysis at tetrahydrofuran (THF) or acetonitrile or contain the hydrochloric ether of 1～3 carbon atom or contain and carry out nucleophilic addition in the alcohol of 3～4 carbon atoms and obtain N-(2,3; 4; 6-"four news" (new ideas pentanoyl glucosyl group)-and the alpha-amino group benzyl cyanide, N-(2,3; 4,6-"four news" (new ideas pentanoyl glucosyl group)-hydrolysis in the hydrogen halide acetic acid solution of alpha-amino group benzyl cyanide obtains described toluylic acid.
3. the preparation method of Arylacetic acids as claimed in claim 1 or 2 is characterized in that described transition metal Lewis acid is one of following:
①SnCl
4 ②ZnCl
2 ③TiCl
4 ④ZnI
2 ⑤CuCl ⑥CuBr⑦CuBr.S(CH
3)
2 ⑧CuCl
2 ⑨CuBr
2。
4. the preparation method of Arylacetic acids as claimed in claim 3 is characterized in that described organic solvent is one of following:
1. 2. 3. 4. 5. acetonitrile of tetrahydrofuran (THF) of Virahol of trichloromethane of methylene dichloride.
5. the preparation method of Arylacetic acids as claimed in claim 4 is characterized in that the hydrogen halide mass content is 30～50% in the described hydrogen halide acetic acid solution, and described hydrogen halide is hydrogen bromide or hydrogen iodide.
6. the preparation method of Arylacetic acids as claimed in claim 4 is characterized in that the described transition metal Lewis acid and the ratio of trimethyl silicane prussiate amount of substance are 1: 1.
7. the preparation method of Arylacetic acids as claimed in claim 1 is characterized in that described method is as follows:
～-20 ℃ (1)-40 under, in being dissolved with the lewis acidic dichloromethane solution of trimethyl silicane prussiate and transition metal, drips the dichloromethane solution that contains N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group) aryl imine;
(2) stir and to be warming up to room temperature and to react, reaction boils off solvent after finishing, residuum dissolves with methylene dichloride, washs after drying, evaporate to dryness again, and evaporate to dryness thing recrystallization in normal heptane obtains N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-the alpha-azyl aryl acetonitrile;
(3) N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-alpha-azyl aryl acetonitrile is dissolved in the dichloromethane solution, drips 45%HBr/HAc solution again, at room temperature kept 1～4 hour, filter, get described Arylacetic acids.
8. the preparation method of Arylacetic acids as claimed in claim 7 is characterized in that described method is as follows:
～-20 ℃ (1)-40 under, in being dissolved with the lewis acidic dichloromethane solution of trimethyl silicane cyanogen compound and transition metal, drip and contain N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group) dichloromethane solution of aryl imine, described trimethyl silicane prussiate, lewis acid catalyst, N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group) ratio of aryl imine amount of substance is 1.25: 1.25: 1;
(2) stir and to be warming up to room temperature and to react, after reaction finishes, boil off solvent, residuum is dissolved in the methylene dichloride, after dichloromethane solution is used the hydrochloric acid, saturated sodium bicarbonate aqueous solution, water washing of 2N successively, use dried over mgso, evaporate to dryness again after the drying, evaporate to dryness thing again in normal heptane recrystallization just obtain N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-the alpha-azyl aryl acetonitrile;
(3) N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-alpha-azyl aryl acetonitrile is dissolved in the dichloromethane solution, drips 45%HBr/HAc solution again, at room temperature keep 1～4 hour after, filter, described Arylacetic acids.
9. the preparation method of Arylacetic acids as claimed in claim 2 is characterized in that described method is as follows:
～-20 ℃ (1)-40 under, in being dissolved with trimethyl silicane prussiate and lewis acidic dichloromethane solution, drip and contain N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group) dichloromethane solution of phenyl imine, trimethyl silicane prussiate, Lewis acid, N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group) the phenyl imine mol ratio is 1.25: 1.25: 1;
(2) stir and to be warming up to room temperature and to react, reaction boils off solvent after finishing, and residuum is dissolved in CH
2Cl
2In, organic layer is used 2N hydrochloric acid, saturated sodium bicarbonate aqueous solution and water washing successively, uses MgSO then
4Drying, evaporate to dryness again after the drying, the evaporate to dryness thing is recrystallization in normal heptane again;
(3) N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group)-alpha-amino group benzyl cyanide is dissolved in the dichloromethane solution, drips 45%HBr/HAc solution again, at room temperature kept 1～4 hour, filter, get the toluylic acid solid.
10. the preparation method of described Arylacetic acids as claimed in claim 3 is characterized in that described formula II N-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group) aryl imine is by formula IN-(2,3,4,6-"four news" (new ideas pentanoyl glucosyl group) amine is substrate, makes through acid catalysis and aldehyde condensation;
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| CNB2005100491663A CN1300090C (en) | 2005-03-02 | 2005-03-02 | Process for preparing aryl acetic acid |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100491663A CN1300090C (en) | 2005-03-02 | 2005-03-02 | Process for preparing aryl acetic acid |
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| CN1300090C true CN1300090C (en) | 2007-02-14 |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2116972A (en) * | 1982-03-24 | 1983-10-05 | Lilly Co Eli | Process for preparing phenylalkanoic acids |
| WO1988000592A1 (en) * | 1986-07-18 | 1988-01-28 | Shell Agrar Gmbh & Co. Kg | DIASTEROSELECTIVE STRECKER SYNTHESIS OF alpha-AMINOACIDS FROM GLYCOSYLAMINE DERIVATES |
| CN1203220A (en) * | 1997-06-16 | 1998-12-30 | 埃勒夫阿托化学有限公司 | Process for continuously preparing aryl alkali salt acetate aqueous solution |
| CN1319081A (en) * | 1998-09-26 | 2001-10-24 | 阿文蒂斯药物德国有限公司 | Method for pressureless production of alpha, alpha-dimethylphenyl acetic acid from alpha, alpha-dimethyl benzyl cyanide |
-
2005
- 2005-03-02 CN CNB2005100491663A patent/CN1300090C/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2116972A (en) * | 1982-03-24 | 1983-10-05 | Lilly Co Eli | Process for preparing phenylalkanoic acids |
| WO1988000592A1 (en) * | 1986-07-18 | 1988-01-28 | Shell Agrar Gmbh & Co. Kg | DIASTEROSELECTIVE STRECKER SYNTHESIS OF alpha-AMINOACIDS FROM GLYCOSYLAMINE DERIVATES |
| CN1203220A (en) * | 1997-06-16 | 1998-12-30 | 埃勒夫阿托化学有限公司 | Process for continuously preparing aryl alkali salt acetate aqueous solution |
| CN1319081A (en) * | 1998-09-26 | 2001-10-24 | 阿文蒂斯药物德国有限公司 | Method for pressureless production of alpha, alpha-dimethylphenyl acetic acid from alpha, alpha-dimethyl benzyl cyanide |
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