CN1328240C - Preparation of benzoyl oxy-aldehyde - Google Patents
Preparation of benzoyl oxy-aldehyde Download PDFInfo
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- CN1328240C CN1328240C CNB2005100215714A CN200510021571A CN1328240C CN 1328240 C CN1328240 C CN 1328240C CN B2005100215714 A CNB2005100215714 A CN B2005100215714A CN 200510021571 A CN200510021571 A CN 200510021571A CN 1328240 C CN1328240 C CN 1328240C
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- 238000002360 preparation method Methods 0.000 title claims description 12
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 title 1
- 238000006243 chemical reaction Methods 0.000 claims abstract description 49
- 238000000034 method Methods 0.000 claims abstract description 15
- 239000002994 raw material Substances 0.000 claims abstract description 12
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims abstract description 9
- 239000004299 sodium benzoate Substances 0.000 claims abstract description 9
- 235000010234 sodium benzoate Nutrition 0.000 claims abstract description 9
- 230000032050 esterification Effects 0.000 claims abstract description 8
- 238000005886 esterification reaction Methods 0.000 claims abstract description 8
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 8
- 230000007062 hydrolysis Effects 0.000 claims abstract description 7
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 claims abstract description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000000741 silica gel Substances 0.000 claims abstract description 5
- 229910002027 silica gel Inorganic materials 0.000 claims abstract description 5
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 26
- 239000002904 solvent Substances 0.000 claims description 23
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 14
- SFCPXHKCMRZQAC-UHFFFAOYSA-N 2,3-dihydroxypropyl benzoate Chemical compound OCC(O)COC(=O)C1=CC=CC=C1 SFCPXHKCMRZQAC-UHFFFAOYSA-N 0.000 claims description 13
- -1 polyoxyethylene Polymers 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 11
- LRWZZZWJMFNZIK-UHFFFAOYSA-N 2-chloro-3-methyloxirane Chemical compound CC1OC1Cl LRWZZZWJMFNZIK-UHFFFAOYSA-N 0.000 claims description 10
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 10
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 9
- XRQKARZTFMEBBY-UHFFFAOYSA-N oxiran-2-ylmethyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1CO1 XRQKARZTFMEBBY-UHFFFAOYSA-N 0.000 claims description 9
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 6
- 239000003444 phase transfer catalyst Substances 0.000 claims description 5
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 4
- SYBYTAAJFKOIEJ-UHFFFAOYSA-N 3-Methylbutan-2-one Chemical compound CC(C)C(C)=O SYBYTAAJFKOIEJ-UHFFFAOYSA-N 0.000 claims description 4
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 4
- 150000003242 quaternary ammonium salts Chemical group 0.000 claims description 4
- 230000001590 oxidative effect Effects 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 238000003408 phase transfer catalysis Methods 0.000 claims description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 abstract description 21
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 abstract description 9
- 239000004327 boric acid Substances 0.000 abstract description 9
- 238000007254 oxidation reaction Methods 0.000 abstract description 4
- 230000003647 oxidation Effects 0.000 abstract description 3
- OQEDEGGYERFFGP-UHFFFAOYSA-N 2-oxoethyl benzoate Chemical compound O=CCOC(=O)C1=CC=CC=C1 OQEDEGGYERFFGP-UHFFFAOYSA-N 0.000 abstract 1
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 239000000243 solution Substances 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 239000011734 sodium Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 238000001035 drying Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 125000005456 glyceride group Chemical group 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- FXSNSRDBXRNAHR-UHFFFAOYSA-N CC(=O)C.[CH2-]C(=O)C.OCC(O)CO Chemical compound CC(=O)C.[CH2-]C(=O)C.OCC(O)CO FXSNSRDBXRNAHR-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 241000872931 Myoporum sandwicense Species 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N dimethylmethane Natural products CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 239000001294 propane Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- KQTXTJOUGJHFLO-UHFFFAOYSA-N benzoyloxyboronic acid Chemical compound OB(O)OC(=O)C1=CC=CC=C1 KQTXTJOUGJHFLO-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 229960000366 emtricitabine Drugs 0.000 description 2
- 150000005826 halohydrocarbons Chemical class 0.000 description 2
- 229960001627 lamivudine Drugs 0.000 description 2
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000000630 rising effect Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- KDVYCTOWXSLNNI-UHFFFAOYSA-N 4-t-Butylbenzoic acid Chemical compound CC(C)(C)C1=CC=C(C(O)=O)C=C1 KDVYCTOWXSLNNI-UHFFFAOYSA-N 0.000 description 1
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 1
- UCAHIIZBPCASHX-UHFFFAOYSA-N CC[N+](CC)(CC)CC1=CC=CC=C1.N Chemical compound CC[N+](CC)(CC)CC1=CC=CC=C1.N UCAHIIZBPCASHX-UHFFFAOYSA-N 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- XQSPYNMVSIKCOC-NTSWFWBYSA-N Emtricitabine Chemical compound C1=C(F)C(N)=NC(=O)N1[C@H]1O[C@@H](CO)SC1 XQSPYNMVSIKCOC-NTSWFWBYSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- QSRFYFHZPSGRQX-UHFFFAOYSA-N benzyl(tributyl)azanium Chemical compound CCCC[N+](CCCC)(CCCC)CC1=CC=CC=C1 QSRFYFHZPSGRQX-UHFFFAOYSA-N 0.000 description 1
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Epoxy Compounds (AREA)
Abstract
The present invention provides a new method for preparing benzoyloxyacetaldehyde (I), which uses sodium benzoate and epichlorohydrin as starting raw material, and 1, 2-bioxhydryl-3-benzoyloxypropane (III) is obtained through esterification and hydrolysis; glycerol and boric acid can also be used as the starting raw material, and III is obtained through complex, the esterification and the hydrolysis; (I) is prepared by III through the oxidation of periodic acid or periodate absorbed on silica gel. The present invention has the advantages of easily obtained raw material, mild reaction condition, convenient operation, high product yield and friendly reaction environment.
Description
Technical field
The invention belongs to the pharmaceutical chemistry field, is the novel preparation method of O-Benzoylglycolaldehyde (I).
Background technology
O-Benzoylglycolaldehyde (I) is the important intermediate of synthetic lamivudine (Lamivudine), emtricitabine nucleoside medicines such as (Emtricitabine).Foreign literature: J Am Chem Soc1939,61:1156～1159 have reported that with the phenylformic acid allyl ester be starting raw material, feed ozone (O in pyruvic acid aqueous solution
3), oxygenolysis obtains O-Benzoylglycolaldehyde; This method operation steps is few, but starting raw material is not easy to obtain, and reaction yield is also lower, and the crude product yield only is 56%; And to use the ozone (O of the big and seriously corroded of toxicity in the reaction
3), bring difficulty for a large amount of preparations, also environment is worked the mischief.Swiss Patent 683613 (CH683613) is with 2-butylene-1, and the two benzoic ethers of 4-glycol are starting raw material, feed ozone (O in ethyl acetate solution
3) oxidation, obtain O-Benzoylglycolaldehyde, though this method operation steps is few, yield height (94.8%), but still have the drawback of using ozone, and the feedstock production difficulty.United States Patent (USP) 5047407 (US5047407) and world patent/9529176 (WO95/29176) have reported that with 1 2-dihydroxyl-3-benzoyloxy propane is raw material, uses NaIO in methylene dichloride/water mixed solvent
4Oxidation makes O-Benzoylglycolaldehyde; This method has overcome the drawback of using ozone, but oxidization-hydrogenation ratio is on the low side, only is 62.14%.Document Can J Research 1933,8:129～136 and Ber 1920,53:1589～1605 have described 1, the synthetic method of 2-dihydroxyl-3-benzoyloxy propane, this method is a starting raw material with glycerol acetonide acetone, under quinoline or triethylamine existence condition with the Benzoyl chloride condensation, obtain glycerol acetonide acetone benzoic ether, in the HCl aqueous solution, take off the acetone protecting group again, promptly get 1,2-dihydroxyl-3-benzoyloxy propane; Because raw materials used glycerol acetonide acetone is not easy to obtain, also need further preparation, so this method exists that synthesis step is many, at the bottom of the complex operation, yield, " three wastes " seriously polluted, high deficiency of cost.
Summary of the invention
The objective of the invention is to be to avoid the deficiency of existing method, the novel method of a kind of yield height, cost is low, reaction conditions is gentle, aftertreatment is easy, reaction environment is friendly preparation O-Benzoylglycolaldehyde (I) is provided.
O-Benzoylglycolaldehyde proposed by the invention (I) novel preparation method is to be starting raw material with Sodium Benzoate cheap and easy to get, epoxy chloropropane or glycerol, boric acid, phenylformic acid, and its synthetic route is as follows:
Method one:
Method two:
For above-mentioned two synthetic routes, its concrete steps are:
A) Sodium Benzoate and epoxy chloropropane esterification make phenylformic acid glycidyl ester (II).
B) compound that is obtained by step a) (II) hydrolysis in acidic aqueous solution gets 1,2-dihydroxyl-3-benzoyloxy propane (III).
C) glycerol and boric acid condensation make boric acid double glyceride (IV).
D) compound that is obtained by step c) (IV) and phenylformic acid esterification get benzoyl boric acid double glyceride (V).
E) compound that is obtained by step d) (V) hydrolysis in acidic aqueous solution gets 1,2-dihydroxyl-3-benzoyloxy propane (III).
F) compound that is obtained by step b) or step e) (III) obtains O-Benzoylglycolaldehyde (I) through oxidation.
Wherein, step (c), step (d) and step (e) but one pot reaction finish.
Each step of this synthetic method specifically describes as follows:
Step a): Sodium Benzoate and epoxy chloropropane through the phase-transfer catalysis esterification, make phenylformic acid glycidyl ester (II) in suitable solvent.Wherein, the solvent that esterification is suitable can be low-molecular-weight ketone as acetone, butanone, methyl isopropyl Ketone, and low-molecular-weight halohydrocarbon is as methylene dichloride, chloroform, 1,2-ethylene dichloride, and aromatic hydrocarbons as: benzene, toluene, chlorobenzene, dimethylbenzene, preferred solvent are toluene and chlorobenzene; Suitable phase-transfer catalyst can be quaternary ammonium salt as Tetrabutylammonium bromide (TBAB), benzyl triethyl ammonium ammonium (TEBA), benzyl tributyl ammonium (TBBA), bromogeramine, polyoxyethylene glycol is as polyoxyethylene glycol-400 (PEG-400), polyoxyethylene glycol-600 (PEG-600), polyoxyethylene glycol-800 (PEG-800), or the composition of quaternary ammonium salt and polyoxyethylene glycol, preferred phase-transfer catalyst is Tetrabutylammonium bromide, polyoxyethylene glycol-400; The mole proportioning of Sodium Benzoate, epoxy chloropropane and phase-transfer catalyst is 1: 1～2.5: 0.01～0.2, and preferred mole proportioning is 1: 1.5: 0.1; Temperature of reaction is room temperature～180 ℃, and preferable reaction temperature is a reflux temperature.
Step b): phenylformic acid glycidyl ester (II) hydrolysis in dilute acid solution gets 1,2-dihydroxyl-3-benzoyloxy propane (III).Wherein, used acid can be mineral acid as sulfuric acid, hydrochloric acid, phosphoric acid, H type Zeo-karb as: 732 types, Dowex-50 type, preferred acid be sulfuric acid and H type 732 Zeo-karbs; Hydrolysising reacting temperature is room temperature～80 ℃, and preferable reaction temperature is 40～60 ℃.
Step c): glycerol and boric acid back flow reaction in solvent makes complex compound boric acid double glyceride (IV) through dehydrating condensation.Wherein, the suitable solvent of complex reaction can be toluene, dimethylbenzene, chlorobenzene, heptane, and preferred solvent is a toluene; The mole proportioning of glycerol and boric acid is 2～2.2: 1, and preferred mole proportioning is 2: 1.
Step d): compound (IV) is without separation, directly with phenylformic acid under acid catalysis, reflux dewatering must benzoyl boric acid double glyceride (V).Wherein, the esterification appropriate catalyst can be protonic acid as HCl, H
2SO
4, tosic acid, or Lewis acid as: FeCl
3, SnCl
4, CuCl
2, preferred catalyst is tosic acid and SnCl
4
Step e): compound (V) is without separation, and directly hydrolysis in acidic aqueous solution gets 1,2-dihydroxyl-3-benzoyloxy propane (III).Wherein, the acid that hydrolysis reaction is suitable is protonic acid as HCl, H
2SO
4, tosic acid, preferred acid is HCl and H
2SO
4Hydrolysising reacting temperature is room temperature～150 ℃, and preferred temperature is a room temperature.
Step f): the compound that step b) or step e) obtain (III) in appropriate solvent, gets O-Benzoylglycolaldehyde (I) through oxidizing reaction.Wherein, the solvent that oxidizing reaction is suitable can be low-molecular-weight halohydrocarbon as methylene dichloride, chloroform, 1, the 2-ethylene dichloride, and preferred solvent is methylene dichloride and chloroform; Used oxygenant can be the Periodic acid that is adsorbed on the silica gel or periodate as NaIO
4, KIO
4Temperature of reaction is a room temperature.
The invention has the advantages that: compared with prior art, this method raw materials used cheap and easy to get, reaction conditions is gentle, easy and simple to handle, yield is high, cost is low, reaction environment is friendly, is fit to a large amount of preparation O-Benzoylglycolaldehydes.
Embodiment
One. the preparation of phenylformic acid glycidyl ester (II)
Embodiment 1
Sodium Benzoate 14.4g (0.1mol), epoxy chloropropane 13.9g (0.15mol), Tetrabutylammonium bromide 3.2g (0.01mol) and toluene 50ml are mixed temperature rising reflux stirring reaction 2 hours.After reaction finishes, filter, filtrate is used 15mL * 2 deionized water wash, and toluene liquid is through anhydrous Na
2SO
4Drying removes solvent and excessive epoxy chloropropane under reduced pressure, gets faint yellow phenylformic acid glycidyl ester oily liquids 16.67g, yield 93.5%.
Embodiment 2
Sodium Benzoate 14.4g (0.1mol), epoxy chloropropane 13.9g (0.15mol), polyoxyethylene glycol-4004.0g (0.01mol) and chlorobenzene 60ml are mixed temperature rising reflux stirring reaction 1.5 hours.Reaction removes by filter small amount of solid after finishing, and filtrate is used 15mL * 2 deionized water wash, and organic layer is through anhydrous Na
2SO
4Drying removes solvent and excessive epoxy chloropropane under reduced pressure, gets faint yellow phenylformic acid glycidyl ester oily liquids 17.08g, yield 95.8%.
Two .1, the preparation of 2-dihydroxyl-3-benzoyloxy propane (III)
Embodiment 1
The aqueous sulfuric acid 120ml that adds phenylformic acid glycidyl ester 21.4g (0.12mol) and 0.05mol/L in reaction flask in 50～55 ℃ of stirring reactions, till oily liquid disappears, needs 3.5 hours approximately.Reaction is cooled to room temperature after finishing, and uses Na
2CO
3Neutralization solution pH adds NaCl to saturated to neutral in solution, mixed solution extracts with ether 60mL * 3, and ether solution is through anhydrous Na
2SO
4After the drying, remove solvent under reduced pressure, get off-white color low melting point solid 20.4g, yield 86.5% after the cooling.
1H-NMR(CDCl
3)δ：8.06(m，2H，Ar-H)，7.56(m，1H，Ar-H)，7.48(m，2H，Ar-H)，4.44(m，2H，PhCOOCH
2)，4.10(t，1H，J＝4.8Hz，CH)，3.81(dd，1H，J＝4.8Hz，7.6Hz，CH
2OH)，3.70(dd，1H，J＝5.6Hz，7.6Hz，CH
2OH)；MS(EI)m/e：196(M
+)。
Embodiment 2
Phenylformic acid glycidyl ester 21.4g (0.12mol), deionized water 120ml and the 732 Zeo-karb 10.0g that are processed into the H type are added in the reaction flask, in 50 ℃ of stirring reactions 2.5 hours.Reaction is cooled to room temperature after finishing, and filters, and adds NaCl in the filtrate to saturated, and mixed solution extracts with ether 60mL * 3, and ether solution is through anhydrous Na
2SO
4After the drying, remove solvent under reduced pressure, cooling gets off-white color low melting point solid 22.72g, yield 96.5%.
Embodiment 3
Glycerol 18.4g (0.2mol), boric acid 6.18g (0.1mol) and toluene 80mL are mixed, and reflux water-dividing reaction under agitation finishes reaction after 5 hours, tell about 5.5mL water.After reaction solution cools off slightly, add phenylformic acid 24.4g (0.2mol) and tosic acid 1.9g (0.01mol), continue reflux water-dividing to reaction and finish, need 7 hours approximately.Reaction removes solvent under reduced pressure after finishing, and remaining oily matter is cooled to room temperature, adds 1.0mol/L aqueous hydrochloric acid 160mL, and the stirring at room reaction was used Na after 2 hours
2CO
3In and pH to neutral, extract ether 100mL * 3, ether solution is through anhydrous Na
2SO
4After the drying, remove solvent under reduced pressure, get off-white color low melting point solid 33.83g, total recovery 86.2% after the cooling.
Embodiment 4
Glycerol 9.2g (0.1mol), boric acid 3.09g (0.05mol) and toluene 50mL are mixed, and reflux water-dividing reaction under agitation finishes reaction after 4 hours, tell about 2.7mL water.After reaction solution cools off slightly, add phenylformic acid 12.2g (0.1mol) and stannic chloride pentahydrate 1.0g, continue reflux water-dividing to reaction and finish, need 5 hours approximately.Reaction removes solvent under reduced pressure after finishing, and remaining oily matter is cooled to room temperature, adds 0.5mol/L aqueous sulfuric acid 100mL, and the stirring at room reaction was used Na after 1.5 hours
2CO
3In and pH to neutral, extract ether 50mL * 3, extracting solution is through anhydrous Na
2SO
4After the drying, remove solvent under reduced pressure, get off-white color low melting point solid 17.52g, total recovery 89.3% after the cooling.
Three. the preparation of O-Benzoylglycolaldehyde (I)
Embodiment 1
In reaction flask, add NaIO
4/ silica gel adsorption thing 30.0g (about 0.04mol) and methylene dichloride 150ml, after stirring, add 1,2-dihydroxyl-3-benzoyloxy propane 3.92g (0.02mol), stirring at room reaction 40 minutes, after reaction finishes, filter a small amount of washed with dichloromethane filter cake, filtrate and washing lotion merge, decompression steams solvent, gets almost colourless oily liquids 3.18g, yield 97.0%.
1H-NMR(CDCl
3)δ：9.72(s，1H，CHO)，8.10(m，2H，Ar-H)，7.61(d，1H，Ar-H)，7.48(m，2H，Ar-H)，4.90(s，2H，CH
2)；MS(EI)m/e：164(M
+)。
Embodiment 2
In reaction flask, add HIO
4/ silica gel adsorption thing 28.0g (about 0.04mol) and chloroform 150ml, after stirring, add 1,2-dihydroxyl-3-benzoyloxy propane 3.92g (0.02mol), stirring at room reaction 1 hour, after reaction finishes, filter the minimum of chloroform washing leaching cake, filtrate and washing lotion merge, decompression steams solvent, gets almost colourless oily liquids 3.05g, yield 92.8%.
The foregoing description only is used to illustrate embodiments of the present invention, but the present invention is not limited only to above-mentioned example.
Claims (5)
1. the novel preparation method of an O-Benzoylglycolaldehyde (I)
It is characterized in that:
A) be starting raw material with Sodium Benzoate and epoxy chloropropane, in solvent,, make phenylformic acid glycidyl ester (II) through the phase-transfer catalysis esterification;
B) compound that is obtained by step a) (II) hydrolysis in dilute acid solution gets 1,2-dihydroxyl-3-benzoyloxy propane (III);
C) compound that is obtained by step b) (III) in appropriate solvent, gets O-Benzoylglycolaldehyde (I) through oxidizing reaction.
2. according to the described method of claim 1, it is characterized in that the suitable solvent of step a) is acetone, butanone, methyl isopropyl Ketone, methylene dichloride, chloroform, 1,2-ethylene dichloride, benzene, toluene, chlorobenzene, dimethylbenzene; Suitable phase-transfer catalyst is the composition of quaternary ammonium salt, polyoxyethylene glycol or quaternary ammonium salt and polyoxyethylene glycol.
3. according to the described method of claim 1, the mole proportioning that it is characterized in that Sodium Benzoate in the step a), epoxy chloropropane and phase-transfer catalyst is 1: 1～2.5: 0.01～0.2; Temperature of reaction is room temperature～180 ℃.
4. according to the described method of claim 1, it is characterized in that the used acid of step b) is mineral acid or H type Zeo-karb; Temperature of reaction is room temperature～80 ℃.
5. according to the described method of claim 1, it is characterized in that the suitable solvent of step c) reaction is methylene dichloride, chloroform, 1, the 2-ethylene dichloride; Used oxygenant is Periodic acid or the periodate that is adsorbed on the silica gel; Temperature of reaction is a room temperature.
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| CN103450024A (en) * | 2013-09-09 | 2013-12-18 | 辽宁石油化工大学 | Preparation method of glycerol monostearate p-hydroxybenzoate |
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| US6228860B1 (en) * | 1990-11-13 | 2001-05-08 | Biochem Pharma Inc. | Substituted 1,3-oxathiolanes with antiviral properties |
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