CN102276559B - Method for synthesizing 3-hydroxymethyl tetrahydrofuran - Google Patents
Method for synthesizing 3-hydroxymethyl tetrahydrofuran Download PDFInfo
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- CN102276559B CN102276559B CN201110231257.4A CN201110231257A CN102276559B CN 102276559 B CN102276559 B CN 102276559B CN 201110231257 A CN201110231257 A CN 201110231257A CN 102276559 B CN102276559 B CN 102276559B
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- Prior art keywords
- butyrolactone
- gamma
- hydroxymethyl
- tetrahydrofuran
- room temperature
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- PCPUMGYALMOCHF-UHFFFAOYSA-N oxolan-3-ylmethanol Chemical compound OCC1CCOC1 PCPUMGYALMOCHF-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 238000000034 method Methods 0.000 title abstract description 12
- 230000002194 synthesizing effect Effects 0.000 title abstract 2
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 claims abstract description 54
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims abstract description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 57
- 238000006243 chemical reaction Methods 0.000 claims description 49
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 44
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 28
- 238000003756 stirring Methods 0.000 claims description 25
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 22
- 239000007788 liquid Substances 0.000 claims description 18
- 238000010792 warming Methods 0.000 claims description 18
- 238000009413 insulation Methods 0.000 claims description 15
- 238000004587 chromatography analysis Methods 0.000 claims description 11
- 238000006467 substitution reaction Methods 0.000 claims description 11
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 238000004440 column chromatography Methods 0.000 claims description 8
- 238000006722 reduction reaction Methods 0.000 claims description 8
- 238000010189 synthetic method Methods 0.000 claims description 6
- SQGFUXSRIIEVCU-UHFFFAOYSA-N 3-(hydroxymethyl)oxolan-2-one Chemical compound OCC1CCOC1=O SQGFUXSRIIEVCU-UHFFFAOYSA-N 0.000 claims description 4
- SCLKNBPNZPAKJH-UHFFFAOYSA-N [Na].OC1C(=O)OCC1=C Chemical compound [Na].OC1C(=O)OCC1=C SCLKNBPNZPAKJH-UHFFFAOYSA-N 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 2
- 238000013019 agitation Methods 0.000 claims description 2
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 2
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 claims description 2
- 230000007935 neutral effect Effects 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 239000012312 sodium hydride Substances 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- -1 ester compound Chemical class 0.000 abstract description 16
- 229910052751 metal Inorganic materials 0.000 abstract description 12
- 239000002184 metal Substances 0.000 abstract description 12
- 239000003054 catalyst Substances 0.000 abstract description 10
- 239000002994 raw material Substances 0.000 abstract description 6
- 230000002378 acidificating effect Effects 0.000 abstract description 5
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 5
- SYNPRNNJJLRHTI-UHFFFAOYSA-N 2-(hydroxymethyl)butane-1,4-diol Chemical compound OCCC(CO)CO SYNPRNNJJLRHTI-UHFFFAOYSA-N 0.000 abstract description 4
- 239000001257 hydrogen Substances 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 238000007142 ring opening reaction Methods 0.000 abstract 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000007789 gas Substances 0.000 description 13
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- 239000000243 solution Substances 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
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000006386 neutralization reaction Methods 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- 0 CC**C(C*)=C1*C*CC1 Chemical compound CC**C(C*)=C1*C*CC1 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 239000010953 base metal Substances 0.000 description 2
- 229910052728 basic metal Inorganic materials 0.000 description 2
- 229910010277 boron hydride Inorganic materials 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 229960004756 ethanol Drugs 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 230000000749 insecticidal effect Effects 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 229920000137 polyphosphoric acid Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- ZFFBIQMNKOJDJE-UHFFFAOYSA-N 2-bromo-1,2-diphenylethanone Chemical compound C=1C=CC=CC=1C(Br)C(=O)C1=CC=CC=C1 ZFFBIQMNKOJDJE-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- RBLVBKCIZRBTBF-UHFFFAOYSA-N C(C)(C)N(C(C)C)CC[Mg] Chemical compound C(C)(C)N(C(C)C)CC[Mg] RBLVBKCIZRBTBF-UHFFFAOYSA-N 0.000 description 1
- YPBMMGMVQOLIBG-UHFFFAOYSA-N CCOC1(CCOC1=O)C(=O)C Chemical compound CCOC1(CCOC1=O)C(=O)C YPBMMGMVQOLIBG-UHFFFAOYSA-N 0.000 description 1
- OARJCTUMPTXKGO-UHFFFAOYSA-N C[O](CC1COCC1)=C Chemical compound C[O](CC1COCC1)=C OARJCTUMPTXKGO-UHFFFAOYSA-N 0.000 description 1
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- ZYOLIONHAKIPDJ-UHFFFAOYSA-N OCC1C=[O]CC1 Chemical compound OCC1C=[O]CC1 ZYOLIONHAKIPDJ-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- GHVZOJONCUEWAV-UHFFFAOYSA-N [K].CCO Chemical compound [K].CCO GHVZOJONCUEWAV-UHFFFAOYSA-N 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical group 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 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
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- VEUUMBGHMNQHGO-UHFFFAOYSA-N ethyl chloroacetate Chemical compound CCOC(=O)CCl VEUUMBGHMNQHGO-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 239000011968 lewis acid catalyst Substances 0.000 description 1
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 1
- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- YWOITFUKFOYODT-UHFFFAOYSA-N methanol;sodium Chemical compound [Na].OC YWOITFUKFOYODT-UHFFFAOYSA-N 0.000 description 1
- CXHHBNMLPJOKQD-UHFFFAOYSA-M methyl carbonate Chemical compound COC([O-])=O CXHHBNMLPJOKQD-UHFFFAOYSA-M 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses a new method for synthesizing 3-hydroxymethyl tetrahydrofuran. In the method, gamma-butyrolactone is used as a main raw material. The method comprises the following steps of: (1) reacting the gamma-butyrolactone and an ester compound (I) containing a carbonyl group or formaldehyde under the action of strong base to generate alpha-substituted gamma-butyrolactone; and (2) reducing the alpha-substituted gamma-butyrolactone by using a metal boron-hydrogen compound directly under the action of a catalyst A to obtain the 3-hydroxymethyl tetrahydrofuran or performing reduction ring-opening reaction of the alpha-substituted gamma-butyrolactone obtained in the step (1) by using the metal boron-hydrogen compound under the action of a metal catalyst B to generate 2-hydroxymethyl-1,4-butanediol, and preparing the 3-hydroxymethyl tetrahydrofuran by using the 2-hydroxymethyl-1,4-butanediol under the action of an acidic catalyst. By the method, yield is high, production cost is low, and low emission is ensured; and the method is simple and suitable for industrial production.
Description
Technical field
The present invention relates to a kind of synthetic method of 3-hydroxymethyl tetrahydrofuran.
Background technology
3-hydroxymethyl tetrahydrofuran compound is the key intermediate of third generation nicotinic insecticide MTI-446, and MTI-446 has remarkable interior suction osmosis as sterilant, and has shown very high insecticidal activity at very low dosage.This medicament low toxicity, the feature such as residual effect is long, and insecticidal spectrum is wide.At present, the document of the synthetic 3-hydroxymethyl tetrahydrofuran method of report is less both at home and abroad.
In WO2005065689, the people such as Gilbert uses diethyl malonate and ethyl chloroacetate reaction to generate 2-ethoxy acyl group-diethyl succinate, and reaction yield is 64% (reaction formula 1); 2-ethoxy acyl group-diethyl succinate reduces and generates 2-methylol-BDO (reaction formula 2) under sodium borohydride, and this reaction yield is that 66%, 2-ethoxy acyl group-diethyl succinate and sodium borohydride ratio are 1:6; 2-methylol-BDO obtains 3-hydroxymethyl tetrahydrofuran (reaction formula 3) through acidic dehydration.
Not only yield is on the low side to use the synthetic 2-ethoxy acyl group-diethyl succinate (reaction formula 1) of diethyl malonate; and 2-ethoxy acyl group-diethyl succinate needs to use a large amount of reductive agents in subsequent reactions (reaction formula 2); not only cost is higher; and reduction reaction emits a large amount of hydrogen, operate more dangerous.After reduction reaction, also need in addition to carry out dehydration reaction and just can obtain 3-hydroxymethyl tetrahydrofuran (reaction formula 3), increased reactions steps.
About cyclization, in JP8291159A, use tosic acid or tosic acid hydrate to dewater, reaction rear impurity is more, needs the separation and purification of column chromatography ability.
Summary of the invention
The technical problem to be solved in the present invention is to provide that a kind of raw material is easy to get, yield is high, environmental friendliness, simple to operate, and is applicable to the synthetic method of industrial 3-hydroxymethyl tetrahydrofuran.
For solving the problems of the technologies described above, the present invention has adopted two kinds of technical schemes, and the gamma-butyrolactone that two kinds of technical schemes are all easy to get take raw material is starting raw material, and its first step has all generated the gamma-butyrolactone of alpha-substitution.
Wherein technical scheme 1 is:
A synthetic method for 3-hydroxymethyl tetrahydrofuran, take gamma-butyrolactone as starting raw material, comprises following preparation process:
(1) substitution reaction: gamma-butyrolactone generates the gamma-butyrolactone of alpha-substitution under highly basic effect with the compound of following general formula (I) or formaldehyde reaction.The gamma-butyrolactone of alpha-substitution exists with two kinds of tautomeric forms.
Wherein, R represents H, Cl, Br, C
1-C
5alkoxyl group or benzyloxy; R
1represent C
1-C
5alkyl or benzyl.
(2) reduction reaction: by the gamma-butyrolactone of the alpha-substitution of gained in step (1) and metal borohydride under catalyst A effect,-5-50 ℃ generation reduction reaction, obtain reduzate, acid neutralization in described reduzate, filtration, precipitation, rectifying obtain 3-hydroxymethyl tetrahydrofuran, and reaction formula is as follows:
Described in step (1), highly basic is organic amino group basic metal, as lithium diisopropylamine, or organic amino group alkaline-earth metal, as diisopropylaminoethyl magnesium; Alkoxy base metal, as sodium amide, potassium amide or Lithamide; Or alkoxy base metal, as sodium methylate, sodium ethylate, sodium tert-butoxide, potassium methylate, potassium ethylate or potassium tert.-butoxide; Or alkalimetal hydride, as NaH or KH.Particular methanol sodium.
In step (1), gamma-butyrolactone and the compound of general formula (I) or the mol ratio of formaldehyde are that 1:1 is to 1:2.0; Reaction conditions is: temperature of reaction-5 ~ 70 ℃, reaction times 0.5 ~ 10h.Reaction solvent A is C
5-C
16alkane, as normal hexane, heptane, octane-iso or sherwood oil; Or C
4-C
10ethers is as THF or methyl tertiary butyl ether; Or simple aromatic hydrocarbons, as toluene or dimethylbenzene.The preferred toluene of described reaction solvent A..
Described in step (2), catalyst A is BF
3or AlCl
3, consumption be reaction mole total amount at 5-20%, preferably 10%; Metal hydroborates is alkali metal boronhydride, as LiBH
4, KBH
4, or NaBH
4.The gamma-butyrolactone of alpha-substitution and the mol ratio of metal borohydride are 1:1-1.5.The solvent of reduction reaction can be ethers (as THF, diisopropyl ether, dibutyl ether, methyl tertiary butyl ether) or alcohols (as methyl alcohol, ethanol, Virahol, the trimethyl carbinol, isopropylcarbinol or propyl carbinol etc.), or any mixture of the two.Temperature of reaction is-5 ~ 50 ℃, and the reaction times is 0.5 ~ 10 hour.
Technical scheme 2 of the present invention is:
Step in technical scheme 1 (2) is substituted by following technical proposals:
By the gamma-butyrolactone of the alpha-substitution of gained in step (1) under metal catalyst B effect, carrying out reductive ring open with metal borohydride reacts, generate 2-methylol-1,4-butyleneglycol, then after acid neutralization, filtering and concentrating, under an acidic catalyst C effect, carry out cyclization, generate 3-hydroxymethyl tetrahydrofuran.
In technique scheme, described metal catalyst B is lewis acid catalyst, for example AlCl
3, ZnCl
2, CaCl
2, MgCl
2, Zn (O
2cCF
3)
2, TiCl
4or Ti (OEt)
4deng, its consumption is the 3-20% of reactant total mole number, preferably 10%; Described metal borohydride is alkali metal boronhydride, as LiBH
4, KBH
4or NaBH
4, or be the derivative compound of basic metal boron hydrogen, as acetic acid foundation sodium borohydride, sodium cyanoborohydride.The gamma-butyrolactone of alpha-substitution and the mol ratio of metal borohydride are 1:1.5-3.0.
The condition of described reductive ring open reaction is: temperature-10 ~ 100 ℃, in 0.5 ~ 10 hour reaction times, the solvent of reductive ring open reaction is alcohol compound, as methyl alcohol, ethanol, Virahol, the trimethyl carbinol, isopropylcarbinol or propyl carbinol etc.
An acidic catalyst C of described cyclization is sulfuric acid, hydrochloric acid, phosphoric acid, polyphosphoric acid, formic acid, tosic acid or methylsulphonic acid, and the ratio of described an acidic catalyst C is 1% to 150% of reactant total mole number.Preferably polyphosphoric acid.The temperature of reaction of cyclization is 10 ~ 200 ℃, and the reaction times is 0.5 ~ 24 hour.
The yield of above-mentioned two steps is 40% ~ 70%.
The beneficial effect that adopts technique scheme to produce is:
(1) metal borohydride usage quantity of the present invention is few, and product yield high energy reaches 70%;
(2) the present invention adopts the gamma-butyrolactone direct-reduction of alpha-substitution to prepare 3-hydroxymethyl tetrahydrofuran, has reduced reactions steps, and technique is simpler, operates more convenient.Be applicable to suitability for industrialized production.
(3) it is less that the present invention produces waste water in building-up process, is the operational path of relative environmental protection.
(4) the present invention adopts raw material cheap and easy to get, and production cost is low, and technological process energy consumption is low,, be applicable to suitability for industrialized production.
Embodiment
embodiment 1:
(1) 1L four-hole bottle adds gamma-butyrolactone 50g, toluene 500mL, sodium methylate 37.7g, open stirring and be warming up to backflow, drip 82.3g diethyl carbonate, dropwise rear insulation reaction 7 hours, be cooled to 0 ℃, drip concentrated hydrochloric acid and be neutralized to neutrality, filter, after concentrating, obtain α-ethoxy acetyl-gamma-butyrolactone colourless liquid 83.7g through column chromatography (chloroform: methyl alcohol=10:1); Yield is 91.1%, TLC: chloroform/methanol, 4:1, Rf=0.6.
(2) add α-ethoxy acetyl gamma-butyrolactone 40g at 500mL four-hole bottle, tetrahydrofuran (THF) 120mL, adds NaBH under room temperature
414.4g, opens and stirs after 30 minutes, adds BF
3(1.7g), stirring at room temperature is progressively warming up to 50 ℃ of reactions after 2 hours, insulation reaction 5 hours, be cooled to 0 ℃, add hydrochloric acid to be neutralized to neutrality, filter, concentrated, rectifying is collected 90 ~ 94/40mmHg cut and is obtained 3-hydroxymethyl tetrahydrofuran colourless liquid 14.2g, and gas chromatographic analysis content is 98%.Yield is 55.0%.
1H-NMR?(CDCl
3)?δ1.60?(m,?1H),?1.98?(m,?1H),?2.19?(m,?1H,?D
2O?exchangeable,?OH),?2.40?(m,?1H),?3.45–3.62?(m,?4H),?3.68–3.88?(m,?2H)；
13C-NMR?(CDCl
3)?δ28.4,?41.2,?64.1,?67.6,?70.4。
embodiment 2
(1) 1L four-hole bottle adds gamma-butyrolactone 50g; toluene 500mL; sodium methylate 37.7g; open stirring and be warming up to backflow, drip 62.8g methylcarbonate, dropwise rear insulation reaction 7 hours; be cooled to 0 ℃; drip concentrated hydrochloric acid and be neutralized to neutrality, filter, after concentrating, obtain alpha-methoxymethyl acyl group-gamma-butyrolactone through column chromatography (chloroform: methyl alcohol=10:1)
-colourless liquid 71.6g; Yield is 85.6%, TLC: chloroform/methanol, 4:1, Rf=0.7.
(2) add alpha-methoxymethyl acyl group gamma-butyrolactone 36.5g at 500mL four-hole bottle, tetrahydrofuran (THF) 120mL, adds NaBH under room temperature
414.4g, opens and stirs after 30 minutes, adds BF
3(1.7g), stirring at room temperature is progressively warming up to 50 ℃ of reactions after 2 hours, insulation reaction 5 hours, be cooled to 0 ℃, add hydrochloric acid to be neutralized to neutrality, filter, concentrated, rectifying is collected 90 ~ 94/40mmHg cut and is obtained 3-hydroxymethyl tetrahydrofuran colourless liquid 13.7g, and gas chromatographic analysis content is 99%.Yield is 53.1%.
embodiment 3:
(1) 1L four-hole bottle adds sherwood oil 500mL, 23.3g sodium hydride (mass content 60%), open the mixing solutions of agitation and dropping 50g gamma-butyrolactone and 34.9g methyl-formiate, drip at approximately 1/10 o'clock, stop dripping, add dehydrated alcohol 3ml, be warming up to 40 ℃, continue to drip mixing solutions.Dropwise rear 40 ℃ of insulation reaction 10 hours, be cooled to room temperature, filter, obtain α-hydroxy methylene-gamma-butyrolactone sodium salt white solid powder 72.9g; Yield is 92.2%.
(2) add α-hydroxy methylene-gamma-butyrolactone sodium salt 40g at 500mL four-hole bottle, tetrahydrofuran (THF) 120mL, is cooled to 0 ℃ and drips 20%HCl methanol solution 53.7g to neutral, is warming up to and under room temperature, adds 13.2g NaBH
4, open and stir after 30 minutes, add BF
3(1.7g), stirring at room temperature is progressively warming up to 50 ℃ of reactions after 2 hours, insulation reaction 5 hours, be cooled to 0 ℃, add hydrochloric acid to be neutralized to neutrality, filter, concentrated, rectifying is collected 90 ~ 94/40mmHg cut and is obtained 3-hydroxymethyl tetrahydrofuran colourless liquid 15.8g, and gas chromatographic analysis content is 98%.Yield is 52.7%.
embodiment 4:
(1) 1L four-hole bottle adds tetrahydrofuran (THF) 400mL, and sodium methylate 45.2g opens and stirs room temperature dropping 60g gamma-butyrolactone solution, dropwises rear stirring 30min, passes into 18.2g formaldehyde gas.After 40 ℃ of insulation reaction 10 hours, be cooled to room temperature, filter, concentrated after through column chromatography (chloroform: methyl alcohol=7:1) alpha-hydroxymethyl-gamma-butyrolactone colourless liquid 61.7g; Yield is 76.2%, TLC: chloroform/methanol, 4:1, Rf=0.5.
(2) add alpha-hydroxymethyl-gamma-butyrolactone 40g at 500mL four-hole bottle, tetrahydrofuran (THF) 120mL, adds NaBH under room temperature
413.1g, opens and stirs after 30 minutes, adds BF
3(2.3g), stirring at room temperature is progressively warming up to 50 ℃ of reactions after 2 hours, insulation reaction 5 hours, be cooled to 0 ℃, add hydrochloric acid to be neutralized to neutrality, filter, concentrated, rectifying is collected 90 ~ 94/40mmHg cut and is obtained 3-hydroxymethyl tetrahydrofuran colourless liquid 23.5g, and gas chromatographic analysis content is 98%.Yield is 66.8%.
embodiment 5:
Different from embodiment mono-:
(2) 500mL four-hole bottle adds α-ethoxy acetyl gamma-butyrolactone 40g, and tetrahydrofuran (THF) 120mL, adds NaBH under room temperature
49.6g, opens and stirs after 30 minutes, adds BF
3(1.7g), stirring at room temperature is after 2 hours, and 25 ℃ are reacted 10 hours, be cooled to 0 ℃, add hydrochloric acid to be neutralized to neutrality, filter, concentrated, rectifying is collected 90 ~ 94/40mmHg cut and is obtained 3-hydroxymethyl tetrahydrofuran colourless liquid 16.8g, and gas chromatographic analysis content is 97.5%.Yield is 40.2%.
embodiment 6
Different from embodiment mono-:
(2) 500mL four-hole bottle adds α-ethoxy acetyl gamma-butyrolactone 40g, and tetrahydrofuran (THF) 120mL, adds NaBH under room temperature
412g, opens and stirs after 30 minutes, adds BF
3(1.7g), stirring at room temperature is warming up to 50 ℃ of reactions 6 hours after 2 hours, be cooled to 0 ℃, add hydrochloric acid to be neutralized to neutrality, filter, concentrated, rectifying is collected 90 ~ 94/40mmHg cut and is obtained 3-hydroxymethyl tetrahydrofuran colourless liquid 11.5g, and gas chromatographic analysis content is 97.2%.Yield is 44.5%.
embodiment 7
Different from embodiment mono-:
(2) 500mL four-hole bottle adds α-ethoxy acetyl gamma-butyrolactone 40g, and trimethyl carbinol 200mL, adds NaBH under room temperature
420g, opens and stirs, and adds 3.4gAlCl
3, drip 24g methyl alcohol, emit a large amount of gas, be progressively warming up to 50 ℃ of reactions, insulation reaction 10 hours, is cooled to 0 ℃, adds hydrochloric acid to be neutralized to neutrality, filters, concentrated.TLC: chloroform/methanol, 4:1, Rf=0.2; Obtain 2-methylol-BDO colourless viscous liquid 24.9g through column chromatography (chloroform: methyl alcohol=8:1), yield is 82%.
Add 2-methylol-1 at 500ml four-hole bottle, 4-butyleneglycol 58g, toluene 200mL, add tosic acid 0.1g, be warming up to back flow reaction 15 hours, be down to room temperature and filter, concentrated, rectifying is collected 90 ~ 94/40mmHg cut and is obtained 3-hydroxymethyl tetrahydrofuran colourless liquid 42g, and gas chromatographic analysis content is 98%.Yield is 85.2%.
embodiment 8
as different from Example 5:
(2) 500mL four-hole bottle adds α-ethoxy acetyl gamma-butyrolactone 40g, and trimethyl carbinol 200mL, adds NaBH under room temperature
414.4g, opens and stirs, and adds 2.8gCaCl
2, drip 24g methyl alcohol, emit a large amount of gas, be progressively warming up to 50 ℃ of reactions, insulation reaction 10 hours, is cooled to 0 ℃, adds hydrochloric acid to be neutralized to neutrality, filters, concentrated.TLC: chloroform/methanol, 4:1, Rf=0.2 obtains 2-methylol-BDO colourless viscous liquid 18.8g through column chromatography (chloroform: methyl alcohol=8:1), and yield is 62%.
500ml four-hole bottle adds 2-methylol-1,4-butyleneglycol 58g, 85% phosphoric acid 83.6g, be warming up to back flow reaction 14 hours, be down to room temperature and drip the neutralization of unsaturated carbonate aqueous solutions of potassium, filter, ethyl acetate 100ml × 3 extraction is concentrated, rectifying is collected 90 ~ 94/40mmHg cut and is obtained 3-hydroxymethyl tetrahydrofuran colourless liquid 42.6g, and gas chromatographic analysis content is 99%.Yield is 86.4%.
embodiment 9
As different from Example 5:
Add α-ethoxy acetyl gamma-butyrolactone 40g at 500ml four-hole bottle, trimethyl carbinol 200mL, adds NaBH under room temperature
428.9g, opens and stirs, and adds 3.4gZnCl
2drip 24g methyl alcohol, emit a large amount of gas, be progressively warming up to 50 ℃ of reactions, insulation reaction 10 hours, is cooled to 0 ℃, adds hydrochloric acid to be neutralized to neutrality, filters, concentrated.TLC: chloroform/methanol, 4:1, Rf=0.2 obtains 2-methylol-BDO colourless viscous liquid 25.8g through column chromatography (chloroform: methyl alcohol=8:1), and yield is 85%.
embodiment 10
The application of 3-hydroxymethyl tetrahydrofuran: 3-is to Methyl benzenesulfonyl oxygen methyltetrahydrofuran in preparation.
Add 3-hydroxymethyl tetrahydrofuran 20g in 500mL four-hole bottle, methylene dichloride 100mL, add Tosyl chloride 44.8g, be cooled to 5 ℃, drip triethylamine 23.8g, dropwise rear room temperature reaction 2 hours, filter, filtrate concentrated 3-to Methyl benzenesulfonyl oxygen methyltetrahydrofuran light yellow liquid 46.2g, gas chromatographic analysis content is 95%, yield is 92.1%.
1H-NMR?(CDCl
3)?δ?1.6?(m,?1H),?2.0?(m,1H),?2.45?(s,?3H)，2.57?(m,?1H),?3.50?(dd,1H,?
J?=?5
.1Hz,?
J?=?9
.5Hz),?3.67~3.79?(m,?3H),?3.91?(dd,?1H,?
J?=?7
.3Hz,?
J?=?9
.5Hz),?3.98?(dd,?1H,?
J?=?6
.6Hz,?
J?=?9
.5Hz)，7.36?(d,?2H,
?J?=?8.5?Hz),?7.79?(d,?2H,?
J?=?8.5?Hz)。
Finally, it is also to be noted that, what more than enumerate is only a specific embodiment of the present invention.Obviously, the invention is not restricted to above embodiment.
Claims (2)
1. a synthetic method for 3-hydroxymethyl tetrahydrofuran, is characterized in that comprising the steps:
(1) substitution reaction
1L four-hole bottle adds sherwood oil 500mL, the sodium hydride 23.3g of mass content 60%, the mixing solutions of unlatching agitation and dropping 50g gamma-butyrolactone and 34.9g methyl-formiate, drips at approximately 1/10 o'clock, stop dripping, add dehydrated alcohol 3ml, be warming up to 40 ℃, continue to drip mixing solutions, dropwise rear 40 ℃ of insulation reaction 10 hours, be cooled to room temperature, filter, obtain α-hydroxy methylene-gamma-butyrolactone sodium salt white solid powder 72.9g; Yield is 92.2%;
(2) reduction reaction
Add α-hydroxy methylene-gamma-butyrolactone sodium salt 40g at 500mL four-hole bottle, tetrahydrofuran (THF) 120mL, is cooled to 0 ℃ and drips 20%HCl methanol solution 53.7g to neutral, is warming up to and under room temperature, adds 13.2g NaBH
4, open and stir after 30 minutes, add 1.7g BF
3, stirring at room temperature is progressively warming up to 50 ℃ of reactions after 2 hours, and insulation reaction 5 hours is cooled to 0 ℃, add hydrochloric acid to be neutralized to neutrality, filter, concentrated, rectifying is collected 90 ~ 94/40mmHg cut and is obtained 3-hydroxymethyl tetrahydrofuran colourless liquid 15.8g, and gas chromatographic analysis content is 98%, and yield is 52.7%.
2. a synthetic method for 3-hydroxymethyl tetrahydrofuran, is characterized in that comprising the steps:
(1) substitution reaction
1L four-hole bottle adds tetrahydrofuran (THF) 400mL, sodium methylate 45.2g, open and stir room temperature dropping 60g gamma-butyrolactone solution, dropwise rear stirring 30min, pass into 18.2g formaldehyde gas, after 40 ℃ of insulation reaction 10 hours, be cooled to room temperature, filter, concentrated after through chloroform: the column chromatography that methyl alcohol is 7:1 obtains alpha-hydroxymethyl-gamma-butyrolactone colourless liquid 61.7g; Yield is 76.2%, TLC: chloroform/methanol, 4:1, Rf=0.5;
(2) reduction reaction
Add alpha-hydroxymethyl-gamma-butyrolactone 40g at 500mL four-hole bottle, tetrahydrofuran (THF) 120mL, adds NaBH under room temperature
413.1g, opens and stirs after 30 minutes, adds 2.3g BF
3, stirring at room temperature is progressively warming up to 50 ℃ of reactions after 2 hours, and insulation reaction 5 hours is cooled to 0 ℃, add hydrochloric acid to be neutralized to neutrality, filter, concentrated, rectifying is collected 90 ~ 94/40mmHg cut and is obtained 3-hydroxymethyl tetrahydrofuran colourless liquid 23.5g, and gas chromatographic analysis content is 98%, and yield is 66.8%.
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| JP5896220B2 (en) * | 2012-03-16 | 2016-03-30 | 三菱レイヨン株式会社 | Method for producing erythritan |
| CN103709126B (en) * | 2013-11-14 | 2018-01-09 | 江苏中旗科技股份有限公司 | The synthetic method of the hydroxymethyl tetrahydrofuran of pesticide dinotefuran intermediate 3 |
| CN104193701B (en) * | 2014-08-25 | 2016-05-25 | 西安近代化学研究所 | A kind of synthetic method of 3-hydroxymethyl tetrahydrofuran |
| CN104311514B (en) * | 2014-10-14 | 2016-06-22 | 安徽扬子化工有限公司 | Method for synthesizing 3-hydroxymethyl tetrahydrofuran ester |
| CN104961710A (en) * | 2015-07-31 | 2015-10-07 | 山东省农药科学研究院 | Synthesis method of dinotefuran |
| CN107226798B (en) * | 2017-06-27 | 2019-12-24 | 成都化润药业有限公司 | Novel process for synthesizing 3-tetrahydrofuran methanol by Prins reaction |
| CN107141273B (en) * | 2017-06-27 | 2020-09-29 | 成都化润药业有限公司 | New process for synthesizing tetrahydrofuran-3-methanol by adopting one-pot method |
| CN109748892B (en) * | 2017-11-08 | 2022-09-20 | 江苏联化科技有限公司 | Preparation method of 3-halogenated tetrahydrofuran |
| CN107793383A (en) * | 2017-12-06 | 2018-03-13 | 成都化润药业有限公司 | A kind of preparation method of 3 hydroxymethyl tetrahydrofuran |
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