CN102126925B - Preparation method of hydroxymethyl cyclane - Google Patents
Preparation method of hydroxymethyl cyclane Download PDFInfo
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- CN102126925B CN102126925B CN201110005549.6A CN201110005549A CN102126925B CN 102126925 B CN102126925 B CN 102126925B CN 201110005549 A CN201110005549 A CN 201110005549A CN 102126925 B CN102126925 B CN 102126925B
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- cyclane
- hydroxymethyl
- cyclobutanemethanol
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- 238000002360 preparation method Methods 0.000 title claims abstract description 28
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 title abstract description 22
- 238000006243 chemical reaction Methods 0.000 claims abstract description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000002156 mixing Methods 0.000 claims abstract description 11
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 30
- WPOPOPFNZYPKAV-UHFFFAOYSA-N cyclobutylmethanol Chemical compound OCC1CCC1 WPOPOPFNZYPKAV-UHFFFAOYSA-N 0.000 claims description 17
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 10
- 239000012044 organic layer Substances 0.000 claims description 10
- 238000013019 agitation Methods 0.000 claims description 9
- 238000009835 boiling Methods 0.000 claims description 9
- 239000011259 mixed solution Substances 0.000 claims description 9
- 238000010992 reflux Methods 0.000 claims description 9
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 13
- 239000003054 catalyst Substances 0.000 abstract description 8
- 239000002994 raw material Substances 0.000 abstract description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract description 6
- 239000002184 metal Substances 0.000 abstract 1
- 230000003472 neutralizing effect Effects 0.000 abstract 1
- GUDMZGLFZNLYEY-UHFFFAOYSA-N cyclopropylmethanol Chemical compound OCC1CC1 GUDMZGLFZNLYEY-UHFFFAOYSA-N 0.000 description 11
- -1 C3-6 cycloalkyl methyl alcohol Chemical compound 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 10
- 238000004821 distillation Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 5
- 229910052700 potassium Inorganic materials 0.000 description 5
- 239000011591 potassium Substances 0.000 description 5
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 4
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 208000030507 AIDS Diseases 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 239000010953 base metal Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- VSSAZBXXNIABDN-UHFFFAOYSA-N cyclohexylmethanol Chemical compound OCC1CCCCC1 VSSAZBXXNIABDN-UHFFFAOYSA-N 0.000 description 2
- XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 description 2
- ISQVBYGGNVVVHB-UHFFFAOYSA-N cyclopentylmethanol Chemical compound OCC1CCCC1 ISQVBYGGNVVVHB-UHFFFAOYSA-N 0.000 description 2
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical group CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- PKAHQJNJPDVTDP-UHFFFAOYSA-N methyl cyclopropanecarboxylate Chemical class COC(=O)C1CC1 PKAHQJNJPDVTDP-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000011787 zinc oxide Substances 0.000 description 2
- QGVLYPPODPLXMB-UBTYZVCOSA-N (1aR,1bS,4aR,7aS,7bS,8R,9R,9aS)-4a,7b,9,9a-tetrahydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-1,1a,1b,4,4a,7a,7b,8,9,9a-decahydro-5H-cyclopropa[3,4]benzo[1,2-e]azulen-5-one Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](O)[C@@]3(O)C(C)(C)[C@H]3[C@@H]21 QGVLYPPODPLXMB-UBTYZVCOSA-N 0.000 description 1
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
- KVVDRQDTODKIJD-UHFFFAOYSA-N 2-cyclopropylacetic acid Chemical compound OC(=O)CC1CC1 KVVDRQDTODKIJD-UHFFFAOYSA-N 0.000 description 1
- XWTWGWCSIXFCEN-UHFFFAOYSA-N 3-methylbutyl cyclopentanecarboxylate Chemical compound CC(C)CCOC(=O)C1CCCC1 XWTWGWCSIXFCEN-UHFFFAOYSA-N 0.000 description 1
- MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 1
- RMOUBSOVHSONPZ-UHFFFAOYSA-N Isopropyl formate Chemical compound CC(C)OC=O RMOUBSOVHSONPZ-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 229910052728 basic metal Inorganic materials 0.000 description 1
- 150000003818 basic metals Chemical class 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 208000012839 conversion disease Diseases 0.000 description 1
- GAKUKXZINODJOH-UHFFFAOYSA-N cyclobutyl formate Chemical compound O=COC1CCC1 GAKUKXZINODJOH-UHFFFAOYSA-N 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- WDABCHFVYNJWNU-UHFFFAOYSA-N formic acid;lithium Chemical compound [Li].OC=O WDABCHFVYNJWNU-UHFFFAOYSA-N 0.000 description 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 150000005826 halohydrocarbons Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000003317 industrial substance Substances 0.000 description 1
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- NETZHAKZCGBWSS-CEDHKZHLSA-N nalbuphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]1(O)CC[C@@H]3O)CN2CC1CCC1 NETZHAKZCGBWSS-CEDHKZHLSA-N 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- MPNNOLHYOHFJKL-UHFFFAOYSA-N peroxyphosphoric acid Chemical compound OOP(O)(O)=O MPNNOLHYOHFJKL-UHFFFAOYSA-N 0.000 description 1
- 238000003408 phase transfer catalysis Methods 0.000 description 1
- QGVLYPPODPLXMB-QXYKVGAMSA-N phorbol Natural products C[C@@H]1[C@@H](O)[C@]2(O)[C@H]([C@H]3C=C(CO)C[C@@]4(O)[C@H](C=C(C)C4=O)[C@@]13O)C2(C)C QGVLYPPODPLXMB-QXYKVGAMSA-N 0.000 description 1
- QEYGAMYURHNUMI-UHFFFAOYSA-N propan-2-yl cyclopropanecarboxylate Chemical compound CC(C)OC(=O)C1CC1 QEYGAMYURHNUMI-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229910052701 rubidium Inorganic materials 0.000 description 1
- IGLNJRXAVVLDKE-UHFFFAOYSA-N rubidium atom Chemical compound [Rb] IGLNJRXAVVLDKE-UHFFFAOYSA-N 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a preparation method of hydroxymethyl cyclane. The method comprises the following steps of: mixing raw materials of naphthenic base carboxylic ether and alcohol corresponding to the naphthenic base carboxylic ether with an alkaline metal catalyst in a certain ratio; carrying out reaction; neutralizing; distilling and the like to obtain hydroxymethyl cyclane.
Description
Technical field
The invention belongs to chemical industry synthesis field, relate to the preparation method of hydroxymethyl cyclane; Relate to the preparation method of C3-6 cycloalkyl methyl alcohol further, further relate to the preparation method of cyclopropyl-carbinol and cyclobutanemethanol.
Background technology
Hydroxymethyl cyclane (shown in following formula I) is important organic solvent and organic synthesis intermediate.As the key intermediate that Cvclopropvlmethvl alcohol is spasmolysis pain medicine and anodyne etc., be also the intermediate for phorbol anti-in Biochemical Research, as acquired immune deficiency syndrome (AIDS) etc.Cyclobutanemethanol is the intermediate of the anodynes such as cloth holder Fino, Nubain.General all water-soluble, the alcohol of hydroxymethyl cyclane, have the chemical property of alcohol, hydroxyl by halo, can become ether with halohydrocarbon, becomes ester with carboxylic acid, oxidable one-tenth aldehyde or carboxylic acid, again can open loop addition, is a kind of industrial chemicals with very big market potentiality.
Wherein: n is the integer of 0,1,2 or 3.
For the synthesis of hydroxymethyl cyclane, existing method has multiple, but from not mentioned take cycloalkyl carboxylate as technique prepared by raw material under alkali-metal existence.
As Chinese patent CN1143065 proposes the method preparing cyclopropyl-carbinol, namely prepared the method for carboxymethyl cyclopropane by cyclopropanecarboxylcompound.Use and do not obtain cyclopropyl-carbinol containing the zinc oxide of chromium for catalyst hydrogenation cyclopropanecarboxylcompound.
The method is with economical and obtain cyclopropyl-carbinol to the mode of environment friendliness, but reaction must by the condition of pressurizeing and heating up and the zinc oxide cost of Chrome-free is higher.
Document [Chinese pharmaceutical chemistry magazine 2003,13 (2) 102-103] reports following scheme:
The method uses with diethyl malonate and 1,3-bromo-chloropropane for starting raw material, closes ring, hydrolysis, decarboxylation one pot reaction obtain cyclobutyl formate through phase-transfer catalysis, and then reduces to obtain cyclobutanemethanol.Although this method reaction conditions is gentle, easy and simple to handle, yield is on the low side is 41%, causes production cost higher.
Document [Tetrahedron letters 1981,22 (36); Yiyao Gongye1988,19 (9): 415-417] reporting following route prepares cyclobutanemethanol:
Ring fourth formic acid lithium aluminium hydride reduction is directly prepared cyclobutanemethanol by the program, and last yield is 72%, and production cost is higher, and lithium aluminum hydride operation is dangerous.
Document [Tetrahedron Letters 1985,26 (31)] reports following operational path:
This route reports and the different reagent such as ω-iodo-1,2-epoxy group(ing) hydride compounds and BuLi is reacted the obtained hydroxy-cyclopentane of different ratios and the mixture of cyclobutanemethanol at Et20 and EtCH2Et.This operational path transformation efficiency is very low, and raw material 6-bromine/iodo-1,2-epoxy group(ing) alkane is difficult to obtain, and final product is difficult to process obtains cyclobutanemethanol.
Summary of the invention
In order to the technological deficiency that the preparation method solving above-mentioned hydroxymethyl cyclane exists.The object of this invention is to provide a kind of preparation method of hydroxymethyl cyclane, relate to the preparation method of C3-6 cycloalkyl methyl alcohol further, further relate to the preparation method of cyclopropyl-carbinol and cyclobutanemethanol.The method raw material is easy to get, and price is low, and synthetic method is simple, and stable and controllable for quality, yield is high, pollutes few.
To achieve these goals, present invention employs following technical scheme:
A kind of preparation method of hydroxymethyl cyclane, the method with cycloalkyl carboxylate, alcohol (alcohol that cycloalkyl carboxylate is corresponding) for raw material, mix according to a certain percentage with the base metal catalysts such as sodium, potassium, through steps such as reaction, neutralization, distillations, obtain hydroxymethyl cyclane.
This process program cost is all lower than original any scheme; Reduce production cost.
In more detail, the feature of the preparation method of hydroxymethyl cyclane of the present invention is: with the alcohol shown in the cycloalkyl carboxylate shown in formula II, formula III for raw material, reacts, obtain the hydroxymethyl cyclane shown in formula I with base metal catalysts after mixing;
Reaction equation is as follows:
In above-mentioned formula I, II or III, n is the integer of 0,1,2 or 3, the alkyl of R to be carbonatoms be 1-6.N is preferably the integer of 1 or 2.
This preparation method of hydroxymethyl cyclane described in invention, is characterized in that taking basic metal as catalyzer.As preferably, be selected from one or more in lithium, sodium, potassium, rubidium.Be more preferably one or more that be selected from sodium, potassium.
This preparation method of hydroxymethyl cyclane described in invention, it is characterized in that: after the reaction, through peroxophosphoric acid neutralization, distillation, obtains the hydroxymethyl cyclane shown in formula I.
This preparation method of hydroxymethyl cyclane described in invention, is characterized in that: the alcohol shown in formula III is the corresponding alcohol of the cycloalkyl carboxylate shown in formula II.
This preparation method of hydroxymethyl cyclane described in invention, is characterized in that, in mole, the usage ratio of cycloalkyl carboxylate and catalyzer is 1: 1.0 ~ 20.0.As preferably, usage ratio is 1: 1.0-10.0, more preferably 1: 1.0-5.0.
This preparation method of hydroxymethyl cyclane described in invention, is characterized in that, in mole, the usage ratio of ester and alcohol is 1: 1.0 ~ 30.0.As preferably, usage ratio is 1: 1: 1.0 ~ 25.0, more preferably 10.0 ~ 15,0.
This preparation method of hydroxymethyl cyclane described in invention, is characterized in that the temperature of reacting is 40 ~ 150 DEG C.As preferably, it is 80 ~ 120 DEG C.
Alcohol is the one in methyl alcohol, ethanol, propyl alcohol, Virahol, propyl carbinol, sec-butyl alcohol, amylalcohol, 2-amylalcohol, 3-amylalcohol, 2-methylpropanol.
This preparation method of hydroxymethyl cyclane described in invention, it is characterized in that reacting and carry out in organic solvent, this organic solvent is selected from hydro carbons, aromatic hydrocarbons etc.Preferred aromatic hydrocarbons, particularly preferably benzene,toluene,xylene etc.
The present invention, owing to have employed above technical scheme, has following positively effect:
1, this programme adopts wherein a kind of raw material providing as proton hydrogen, facilitates reaction conversion ratio, improves yield and the quality product of product.
2, catalysts selects the basic catalysts such as sodium Metal 99.5, greatly improves the yield of reaction, makes existing yield be up to 90%, exceeds all far away than original any scheme.
3, boil before gained in distilling and can be used for lower secondary response, achieve recycled, make the program reach the requirement of Green Chemistry.
Embodiment
Below by preferred embodiment, preferred forms of the present invention is described; here embodiment is to explain the present invention; and should not be construed as limitation of the present invention; when not departing from spirit of the present invention and essential scope; can make various changes and modifications, these all should be included within protection scope of the present invention.
Embodiment 1
The present embodiment illustrates the preparation of cyclopropyl-carbinol
By 150g sodium Metal 99.5,500g toluene, add in the four-hole boiling flask being furnished with electric mixing device, thermometer, constant pressure funnel and reflux condensing tube, under agitation mixed solution (Virahol 940g+ cyclopropanecarboxylic acid isopropyl ester 180g) is added drop-wise in described flask, continue reaction with 6 hours, temperature of reaction is 90-110 DEG C.Slowly added in described flask by the phosphoric acid of 682g 80%, separate organic layer, organic layer, through distillation, obtains product.
Cyclopropyl-carbinol yield is 89.6%, and content is greater than 99.0%.
Embodiment 2
The present embodiment illustrates the preparation of cyclopropyl-carbinol
By 150g sodium Metal 99.5,500g toluene, add in the four-hole boiling flask being furnished with electric mixing device, thermometer, constant pressure funnel and reflux condensing tube, under agitation mixed solution (sec-butyl alcohol 972g+ cyclopropanecarboxylic acid methyl esters 112g) is added drop-wise in described flask, continue reaction with 6 hours, temperature of reaction is 95-110 DEG C, and all the other are all with embodiment 1.
Cyclopropyl-carbinol yield is 89.4%, and content is greater than 99.0%.
Embodiment 3
The present embodiment illustrates the preparation of cyclopropyl-carbinol
By 150g sodium Metal 99.5,500g toluene, add in the four-hole boiling flask being furnished with electric mixing device, thermometer, constant pressure funnel and reflux condensing tube, under agitation mixed solution (ethanol 720g+ cyclopropanecarboxylic acid methyl esters 160g) is added drop-wise in described flask, continue reaction with 6 hours, temperature of reaction is 90-110 DEG C, and all the other are all with embodiment 1.
Cyclopropyl-carbinol yield is 89.3%, and content is greater than 99.0%.
Embodiment 4
The present embodiment illustrates the preparation of cyclobutanemethanol
By 150g sodium Metal 99.5,500g toluene, add in the four-hole boiling flask being furnished with electric mixing device, thermometer, constant pressure funnel and reflux condensing tube, under agitation mixed solution (Virahol 998g+ ring fourth isopropyl formate 196g) is added drop-wise in described flask, continue reaction with 6 hours, temperature of reaction is 90-110 DEG C.Slowly added in described flask by the phosphoric acid of 682g 80%, separate organic layer, organic layer, through distillation, obtains product.
Cyclobutanemethanol yield is 80.8%, and content is greater than 98.0%.
Embodiment 5
The present embodiment illustrates the preparation of cyclobutanemethanol
By 150g sodium Metal 99.5,500g toluene, add in the four-hole boiling flask being furnished with electric mixing device, thermometer, constant pressure funnel and reflux condensing tube, under agitation mixed solution (methyl alcohol 500g+ ring fourth methyl-formiate 145g) is added drop-wise in described flask, continue reaction with 6 hours, temperature of reaction is 90-110 DEG C, and all the other are all with embodiment 4.
Cyclobutanemethanol yield is 89.4%, and content is greater than 99.0%.
Embodiment 6
The present embodiment illustrates the preparation of cyclobutanemethanol
By 150g sodium Metal 99.5,500g toluene, add in the four-hole boiling flask being furnished with electric mixing device, thermometer, constant pressure funnel and reflux condensing tube, under agitation mixed solution (ethanol 720g+ ring fourth ethyl formate 165g) is added drop-wise in described flask, continue reaction with 6 hours, temperature of reaction is 90-110 DEG C, and all the other are all with embodiment 4.
Cyclobutanemethanol yield is 89.9%, and content is greater than 99.0%.
Embodiment 7
The present embodiment illustrates the preparation of cyclopentyl carbinol
By 150g sodium Metal 99.5,500g toluene, add in the four-hole boiling flask being furnished with electric mixing device, thermometer, constant pressure funnel and reflux condensing tube, under agitation mixed solution (primary isoamyl alcohol 1378g+ cyclopentanecarboxylic acid isopentyl ester 263g) is added drop-wise in described flask, continue reaction with 6 hours, temperature of reaction is 110-130 DEG C.Slowly added in described flask by the phosphoric acid of 682g 80%, separate organic layer, organic layer, through distillation, obtains product.
Cyclopentyl carbinol yield is 86.0%, and content is greater than 99.0%.
Embodiment 8
The present embodiment illustrates the preparation of hexahydrobenzyl alcohol
By 150g sodium Metal 99.5,500g toluene, add in the four-hole boiling flask being furnished with electric mixing device, thermometer, constant pressure funnel and reflux condensing tube, under agitation mixed solution (the secondary own ester 303g of secondary hexyl alcohol 1598g+ heptanaphthenic acid) is added drop-wise in described flask, continue reaction with 6 hours, temperature of reaction is 110-140 DEG C.Slowly added in described flask by the phosphoric acid of 682g 80%, separate organic layer, organic layer, through distillation, obtains product.
Hexahydrobenzyl alcohol yield is 80.7%, and content is greater than 99.0%.
Embodiment 9-11
According to the step that embodiment 1-3 is identical, except potassium is as except catalyzer, all the other operating process are equal to.
Table 1 embodiment 9 ~ 11 catalyst levels and processing condition thereof and result
Embodiment 12-14
According to the step that embodiment 4-6 is identical, except potassium is as except catalyzer, all the other operating process are equal to.
Table 2 embodiment 12 ~ 14 catalyst levels and processing condition thereof and result
Claims (1)
1. the preparation method of a cyclobutanemethanol, it is characterized in that: by 150g sodium Metal 99.5,500g toluene, add in the four-hole boiling flask being furnished with electric mixing device, thermometer, constant pressure funnel and reflux condensing tube, under agitation the mixed solution of ethanol 720g and ring fourth ethyl formate 165g is added drop-wise in described flask, continue reaction with 6 hours, temperature of reaction is 90-110 DEG C, the phosphoric acid of 682g80% is slowly added in described flask, separate organic layer, organic layer distills, and obtains cyclobutanemethanol; Cyclobutanemethanol yield is 89.9%, and content is greater than 99.0%.
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| GB351359A (en) * | 1929-11-25 | 1931-06-25 | H Th Boehme Ag | Improvements in or relating to the production of primary alcohols |
| GB589380A (en) * | 1941-07-02 | 1947-06-18 | Innovations Chimiques Sinnova | Improved process for the manufacture of alcohol of high molecular weight |
| US3280199A (en) * | 1962-09-27 | 1966-10-18 | Universal Oil Prod Co | Preparation of primary alcohols |
| US4189615A (en) * | 1976-06-11 | 1980-02-19 | Phillips Petroleum Company | Preparation of alcohols by treating esters with alkali metal borohydride |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB351359A (en) * | 1929-11-25 | 1931-06-25 | H Th Boehme Ag | Improvements in or relating to the production of primary alcohols |
| GB589380A (en) * | 1941-07-02 | 1947-06-18 | Innovations Chimiques Sinnova | Improved process for the manufacture of alcohol of high molecular weight |
| US3280199A (en) * | 1962-09-27 | 1966-10-18 | Universal Oil Prod Co | Preparation of primary alcohols |
| US4189615A (en) * | 1976-06-11 | 1980-02-19 | Phillips Petroleum Company | Preparation of alcohols by treating esters with alkali metal borohydride |
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| An Improved Bouveault-Blanc Ester Reduction with Stabilized Alkali Metals;Brian S.Bodnar,Paul F.Vogt;《J.Org.Chem》;20090216;第74卷;第2598-2600页 * |
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