CN105017017B - The preparation method of cycloalkyl formic acid ester compound - Google Patents
The preparation method of cycloalkyl formic acid ester compound Download PDFInfo
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- -1 cycloalkyl formic acid ester compound Chemical class 0.000 title claims abstract description 62
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 title abstract 8
- 235000019253 formic acid Nutrition 0.000 title abstract 4
- 238000006243 chemical reaction Methods 0.000 claims abstract description 17
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229910002091 carbon monoxide Inorganic materials 0.000 claims abstract description 9
- 150000002940 palladium Chemical class 0.000 claims abstract description 7
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- 150000002978 peroxides Chemical class 0.000 claims abstract description 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- 229920001343 polytetrafluoroethylene Polymers 0.000 claims description 9
- 239000004810 polytetrafluoroethylene Substances 0.000 claims description 9
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 8
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical group ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 7
- XPNGNIFUDRPBFJ-UHFFFAOYSA-N (2-methylphenyl)methanol Chemical compound CC1=CC=CC=C1CO XPNGNIFUDRPBFJ-UHFFFAOYSA-N 0.000 claims description 6
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 6
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 6
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical group Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 claims description 4
- MSHFRERJPWKJFX-UHFFFAOYSA-N 4-Methoxybenzyl alcohol Chemical compound COC1=CC=C(CO)C=C1 MSHFRERJPWKJFX-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- 239000003446 ligand Substances 0.000 claims description 4
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 4
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 claims description 3
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 3
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 3
- PTHGDVCPCZKZKR-UHFFFAOYSA-N (4-chlorophenyl)methanol Chemical compound OCC1=CC=C(Cl)C=C1 PTHGDVCPCZKZKR-UHFFFAOYSA-N 0.000 claims description 2
- GEZMEIHVFSWOCA-UHFFFAOYSA-N (4-fluorophenyl)methanol Chemical compound OCC1=CC=C(F)C=C1 GEZMEIHVFSWOCA-UHFFFAOYSA-N 0.000 claims description 2
- AXCHZLOJGKSWLV-UHFFFAOYSA-N (4-phenylphenyl)methanol Chemical compound C1=CC(CO)=CC=C1C1=CC=CC=C1 AXCHZLOJGKSWLV-UHFFFAOYSA-N 0.000 claims description 2
- WAPNOHKVXSQRPX-SSDOTTSWSA-N (R)-1-phenylethanol Chemical compound C[C@@H](O)C1=CC=CC=C1 WAPNOHKVXSQRPX-SSDOTTSWSA-N 0.000 claims description 2
- WAPNOHKVXSQRPX-ZETCQYMHSA-N (S)-1-phenylethanol Chemical compound C[C@H](O)C1=CC=CC=C1 WAPNOHKVXSQRPX-ZETCQYMHSA-N 0.000 claims description 2
- WAPNOHKVXSQRPX-UHFFFAOYSA-N 1-phenylethanol Chemical compound CC(O)C1=CC=CC=C1 WAPNOHKVXSQRPX-UHFFFAOYSA-N 0.000 claims description 2
- JJCKHVUTVOPLBV-UHFFFAOYSA-N 3-Methylbenzyl alcohol Chemical compound CC1=CC=CC(CO)=C1 JJCKHVUTVOPLBV-UHFFFAOYSA-N 0.000 claims description 2
- MOOUWXDQAUXZRG-UHFFFAOYSA-N 4-(trifluoromethyl)benzyl alcohol Chemical compound OCC1=CC=C(C(F)(F)F)C=C1 MOOUWXDQAUXZRG-UHFFFAOYSA-N 0.000 claims description 2
- KMTDMTZBNYGUNX-UHFFFAOYSA-N 4-methylbenzyl alcohol Chemical compound CC1=CC=C(CO)C=C1 KMTDMTZBNYGUNX-UHFFFAOYSA-N 0.000 claims description 2
- BWVAOONFBYYRHY-UHFFFAOYSA-N [4-(hydroxymethyl)phenyl]methanol Chemical compound OCC1=CC=C(CO)C=C1 BWVAOONFBYYRHY-UHFFFAOYSA-N 0.000 claims description 2
- VEDDBHYQWFOITD-UHFFFAOYSA-N para-bromobenzyl alcohol Chemical compound OCC1=CC=C(Br)C=C1 VEDDBHYQWFOITD-UHFFFAOYSA-N 0.000 claims description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims description 2
- MFGWMAAZYZSWMY-UHFFFAOYSA-N (2-naphthyl)methanol Chemical compound C1=CC=CC2=CC(CO)=CC=C21 MFGWMAAZYZSWMY-UHFFFAOYSA-N 0.000 claims 2
- PBLNHHSDYFYZNC-UHFFFAOYSA-N (1-naphthyl)methanol Chemical compound C1=CC=C2C(CO)=CC=CC2=C1 PBLNHHSDYFYZNC-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 8
- 150000001875 compounds Chemical class 0.000 abstract description 6
- 239000003814 drug Substances 0.000 abstract description 5
- 238000005810 carbonylation reaction Methods 0.000 abstract description 3
- 208000002551 irritable bowel syndrome Diseases 0.000 abstract description 3
- 229930014626 natural product Natural products 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 239000002243 precursor Substances 0.000 abstract description 2
- 239000000376 reactant Substances 0.000 abstract description 2
- 230000001476 alcoholic effect Effects 0.000 abstract 2
- 208000007101 Muscle Cramp Diseases 0.000 abstract 1
- 230000006315 carbonylation Effects 0.000 abstract 1
- CURUTKGFNZGFSE-UHFFFAOYSA-N dicyclomine Chemical compound C1CCCCC1C1(C(=O)OCCN(CC)CC)CCCCC1 CURUTKGFNZGFSE-UHFFFAOYSA-N 0.000 abstract 1
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract 1
- 230000003647 oxidation Effects 0.000 abstract 1
- 238000007254 oxidation reaction Methods 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 59
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 15
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 12
- 238000004440 column chromatography Methods 0.000 description 6
- 235000019445 benzyl alcohol Nutrition 0.000 description 5
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 5
- 229940079593 drug Drugs 0.000 description 3
- 208000005392 Spasm Diseases 0.000 description 2
- 239000004809 Teflon Substances 0.000 description 2
- 229920006362 Teflon® Polymers 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical compound C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- JWAZRIHNYRIHIV-UHFFFAOYSA-N 2-naphthol Chemical compound C1=CC=CC2=CC(O)=CC=C21 JWAZRIHNYRIHIV-UHFFFAOYSA-N 0.000 description 1
- 208000007530 Essential hypertension Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 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
- 230000004071 biological effect Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- VBWFYEFYHJRJER-UHFFFAOYSA-N methyl 4-(hydroxymethyl)benzoate Chemical compound COC(=O)C1=CC=C(CO)C=C1 VBWFYEFYHJRJER-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000005832 oxidative carbonylation reaction Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/36—Preparation of carboxylic acid esters by reaction with carbon monoxide or formates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/74—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/74—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
- C07C69/75—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring of acids with a six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
技术领域technical field
本发明涉及一种环烷基甲酸酯化合物的制备方法，属于有机合成领域。The invention relates to a preparation method of cycloalkyl formate compounds, belonging to the field of organic synthesis.
背景技术Background technique
环烷基甲酸酯化合物是一类非常重要的羰基化合物，其骨架广泛存在于许多具有生物活性的天然产物和药物中。因其特殊的生理活性和药性，一直以来都是有机化学家和药物化学家的研究热点。环烷基甲酸酯化合物可用于治疗胃肠道痉挛、肠易激综合征、原发性高血压及心力衰竭等疾病的药物。环烷基甲酸酯化合物的传统制备方法包括卤代环烷烃化合物与醇化合物的羰基化反应或是环烷基甲酸化合物与醇化合物的酯化反应等等。尽管这些方法能够制备得到目标产物，但是反应所使用的起始原料比较复杂，条件也比较繁琐，反应的原子经济性普遍比较低，选择性也不是很好。Naphthenic carboxylate compounds are a very important class of carbonyl compounds, and their skeletons are widely found in many natural products and drugs with biological activity. Because of its special physiological activity and medicinal properties, it has always been a research hotspot of organic chemists and medicinal chemists. The naphthenic carboxylate compound can be used as a drug for treating gastrointestinal spasm, irritable bowel syndrome, essential hypertension, heart failure and other diseases. The traditional preparation methods of naphthenic acid ester compounds include the carbonylation reaction of halogenated cycloalkane compound and alcohol compound or the esterification reaction of naphthenic acid compound and alcohol compound, etc. Although these methods can prepare the target product, the starting materials used in the reaction are relatively complicated, the conditions are relatively cumbersome, the atom economy of the reaction is generally low, and the selectivity is not very good.
发明内容Contents of the invention
本发明所要解决的问题在于提供一种简单、原子经济性高并且适用范围广的环烷基甲酸酯化合物的制备方法。The problem to be solved by the present invention is to provide a simple method for preparing naphthenic carboxylate compounds with high atom economy and wide application range.
本发明所提供的技术方案具体如下：The technical scheme provided by the present invention is specifically as follows:
一种环烷基甲酸酯化合物的制备方法，包括以下步骤：在反应器中加入钯盐、膦配体、环烷烃化合物、有机溶剂、醇化合物和过氧化物，混合均匀，然后将反应器放入高压反应釜中，在一氧化碳气氛、90～120℃条件下反应16～24小时，随后分离并纯化，即得到环烷基甲酸酯化合物，其反应式为：A preparation method of naphthenic formate compound, comprising the following steps: adding palladium salt, phosphine ligand, cycloalkane compound, organic solvent, alcohol compound and peroxide into a reactor, mixing evenly, and then putting the reactor into Put it in a high-pressure reactor, react in a carbon monoxide atmosphere at 90-120°C for 16-24 hours, and then separate and purify to obtain a naphthenic carboxylate compound. The reaction formula is:
其中，R1-H为环烷烃化合物，R2OH为醇化合物。Wherein, R 1 -H is a cycloalkane compound, and R 2 OH is an alcohol compound.
所述的环烷烃化合物、醇化合物、钯盐、膦配体和过氧化物的摩尔量之比为50～70：1：0.01～0.05：0.02～0.10：1.8～2.0。The molar ratio of the cycloalkane compound, alcohol compound, palladium salt, phosphine ligand and peroxide is 50-70:1:0.01-0.05:0.02-0.10:1.8-2.0.
所述的钯盐为氯化钯、醋酸钯或三(二亚苄基丙酮)二钯。The palladium salt is palladium chloride, palladium acetate or tris(dibenzylideneacetone) dipalladium.
所述的有机溶剂为1,2-二氯乙烷或乙腈。The organic solvent is 1,2-dichloroethane or acetonitrile.
所述的环烷烃化合物为环己烷或环戊烷。The cycloalkane compound is cyclohexane or cyclopentane.
所述的醇化合物为苯甲醇、2-甲基苯甲醇、3-甲基苯甲醇、4-甲基苯甲醇、4-甲氧基苯甲醇、4-氟苯甲醇、4-氯苯甲醇、4-溴苯甲醇、4-三氟甲基苯甲醇、4-苯基苯甲醇、4-羟甲基苯甲酸甲酯、1,4-苯二甲醇、2-萘甲醇、1-萘甲醇、1-苯基乙醇、(S)-(-)-1-苯乙醇、(R)-(+)-1-苯乙醇、2-苯基乙醇、乙醇或正丁醇。Described alcohol compound is benzyl alcohol, 2-methylbenzyl alcohol, 3-methylbenzyl alcohol, 4-methylbenzyl alcohol, 4-methoxybenzyl alcohol, 4-fluorobenzyl alcohol, 4-chlorobenzyl alcohol, 4-Bromobenzyl alcohol, 4-trifluoromethyl benzyl alcohol, 4-phenyl benzyl alcohol, 4-hydroxymethyl benzoic acid methyl ester, 1,4-benzenedimethanol, 2-naphthyl alcohol, 1-naphthyl alcohol, 1-phenylethanol, (S)-(-)-1-phenylethanol, (R)-(+)-1-phenylethanol, 2-phenylethanol, ethanol or n-butanol.
所述的反应器为聚四氟乙烯管。The reactor is a polytetrafluoroethylene tube.
与现有技术相比，本发明具有以下优点和有益效果：Compared with the prior art, the present invention has the following advantages and beneficial effects:
本发明所用反应物都廉价易得，反应条件非常简单，原子经济性很高，并且可以选择性非常高地实现环烷烃化合物与醇化合物的氧化羰基化反应，从而得到环烷基甲酸酯化合物。本方法可以简单地制备出具有广泛应用的治疗胃肠道痉挛和肠易激综合征的药物双环维林的前体。本发明在药物合成，天然产物等的合成中有很多的应用潜力。The reactants used in the invention are all cheap and easy to obtain, the reaction conditions are very simple, the atom economy is high, and the oxidative carbonylation reaction of cycloalkane compound and alcohol compound can be realized with very high selectivity, so as to obtain cycloalkyl formate compound. The method can simply prepare the precursor of dicyclvirine, which is widely used in the treatment of gastrointestinal spasm and irritable bowel syndrome. The present invention has many application potentials in the synthesis of medicines, natural products and the like.
具体实施方式detailed description
下面的实施例可以使本专业技术人员更全面地理解本发明，但不以任何方式限制本发明。本发明所用原料均为已知化合物，可由市场购得，或可采用本领域已知的方法合成。The following examples can enable those skilled in the art to understand the present invention more comprehensively, but do not limit the present invention in any way. The raw materials used in the present invention are all known compounds, which can be purchased from the market, or can be synthesized by methods known in the art.
实施例1Example 1
在聚四氟乙烯管中加入氯化钯(0.01mmol)、三苯基膦(0.02mmol)、环己烷(1.5mL)、1,2-二氯乙烷(0.5mL)、苯甲醇(0.20mmol)和过氧化二叔丁基(0.36mmol)，混合均匀，然后将聚四氟乙烯管放入高压反应釜中，体系置换为5个大气压的一氧化碳气氛，在110℃下反应20小时；停止反应，柱层析得产品环己甲酸苄酯化合物。(使用其他的常规分离纯化的方法也可以得到产品。)Add palladium chloride (0.01mmol), triphenylphosphine (0.02mmol), cyclohexane (1.5mL), 1,2-dichloroethane (0.5mL), benzyl alcohol (0.20 mmol) and di-tert-butyl peroxide (0.36mmol), mix well, then put the polytetrafluoroethylene tube into the autoclave, replace the system with a carbon monoxide atmosphere of 5 atmospheres, and react at 110°C for 20 hours; stop Reaction, column chromatography to obtain the product benzyl cyclohexanecarboxylate compound. (The product can also be obtained by using other conventional separation and purification methods.)
实施例2Example 2
在聚四氟乙烯管中加入醋酸钯(0.01mmol)、三苯基膦(0.02mmol)、环己烷(1.5mL)、1,2-二氯乙烷(0.5mL)、苯甲醇(0.20mmol)和过氧化二叔丁基(0.36mmol)，混合均匀，然后将聚四氟乙烯管放入高压反应釜中，体系置换为5个大气压的一氧化碳气氛，在120℃下反应18小时。停止反应，柱层析得产品环己甲酸苄酯化合物。Add palladium acetate (0.01mmol), triphenylphosphine (0.02mmol), cyclohexane (1.5mL), 1,2-dichloroethane (0.5mL), benzyl alcohol (0.20mmol ) and di-tert-butyl peroxide (0.36mmol), mix well, then put the polytetrafluoroethylene tube into the autoclave, replace the system with a carbon monoxide atmosphere of 5 atmospheres, and react at 120°C for 18 hours. The reaction was stopped, and the product benzyl cyclohexanecarboxylate compound was obtained by column chromatography.
实施例3Example 3
在聚四氟乙烯管中加入三(二亚苄基丙酮)二钯(0.005mmol)、三苯基膦(0.02mmol)、环己烷(1.5mL)、1,2-二氯乙烷(0.5mL)、苯甲醇(0.20mmol)和过氧化二叔丁基(0.36mmol)，将聚四氟乙烯管放入高压反应釜中，体系置换为5个大气压的一氧化碳气氛，在100℃下反应16小时。停止反应，柱层析得产品环己甲酸苄酯化合物。Add tris(dibenzylideneacetone)dipalladium (0.005mmol), triphenylphosphine (0.02mmol), cyclohexane (1.5mL), 1,2-dichloroethane (0.5 mL), benzyl alcohol (0.20mmol) and di-tert-butyl peroxide (0.36mmol), put the polytetrafluoroethylene tube into the autoclave, replace the system with a carbon monoxide atmosphere of 5 atmospheres, and react at 100°C for 16 Hour. The reaction was stopped, and the product benzyl cyclohexanecarboxylate compound was obtained by column chromatography.
实施例4Example 4
在聚四氟乙烯管中加入氯化钯(0.01mmol)、三苯基膦(0.02mmol)、环己烷(1.5mL)、乙腈(0.5mL)、苯甲醇(0.20mmol)和过氧化二叔丁基(0.36mmol)，混合均匀，然后将聚四氟乙烯管放入高压反应釜中，体系置换为5个大气压的一氧化碳气氛，在90℃下反应24小时。停止反应，柱层析得产品环己甲酸苄酯化合物。Add palladium chloride (0.01mmol), triphenylphosphine (0.02mmol), cyclohexane (1.5mL), acetonitrile (0.5mL), benzyl alcohol (0.20mmol) and di-tert-peroxide in a Teflon tube Butyl (0.36mmol), mixed evenly, then put the polytetrafluoroethylene tube into the autoclave, replace the system with a carbon monoxide atmosphere of 5 atmospheres, and react at 90°C for 24 hours. The reaction was stopped, and the product benzyl cyclohexanecarboxylate compound was obtained by column chromatography.
实施例5Example 5
在聚四氟乙烯管中，加入氯化钯(0.01mmol)、三苯基膦(0.02mmol)、环戊烷(1.5mL)、1,2-二氯乙烷(0.5mL)、苯甲醇(0.20mmol)和过氧化二叔丁基(0.36mmol)，混合均匀，然后将聚四氟乙烯管放入高压反应釜中，体系置换为5个大气压的一氧化碳气氛，在110℃下反应22小时；停止反应，柱层析得产品环戊甲酸苄酯化合物。In a Teflon tube, add palladium chloride (0.01 mmol), triphenylphosphine (0.02 mmol), cyclopentane (1.5 mL), 1,2-dichloroethane (0.5 mL), benzyl alcohol ( 0.20mmol) and di-tert-butyl peroxide (0.36mmol), mix evenly, then put the polytetrafluoroethylene tube into the autoclave, replace the system with a carbon monoxide atmosphere of 5 atmospheres, and react at 110°C for 22 hours; The reaction was stopped, and the product benzyl cyclopentacarboxylate compound was obtained by column chromatography.
实施例6-24Example 6-24
实施例6-24中除了使用的醇化合物不同外，其他反应条件相同，具体为：在聚四氟乙烯管中，加入氯化钯(0.01mmol)、三苯基膦(0.02mmol)、环己烷(1.5mL)、1,2-二氯乙烷(0.5mL)、醇化合物(0.20mmol)和过氧化二叔丁基(0.36mmol)，混合均匀，然后将聚四氟乙烯管放入高压反应釜中，体系置换为5个大气压的一氧化碳气氛，在110℃下反应24小时。停止反应，柱层析得产品环己甲酸酯化合物。In Example 6-24, except that the alcohol compound used is different, other reaction conditions are the same, specifically: in a polytetrafluoroethylene tube, add palladium chloride (0.01mmol), triphenylphosphine (0.02mmol), cyclohexyl alkane (1.5mL), 1,2-dichloroethane (0.5mL), alcohol compound (0.20mmol) and di-tert-butyl peroxide (0.36mmol), mix well, and then put the polytetrafluoroethylene tube into the high-pressure In the reaction kettle, the system was replaced with a carbon monoxide atmosphere of 5 atmospheres, and the reaction was carried out at 110° C. for 24 hours. The reaction was stopped, and the product cyclohexyl carboxylate compound was obtained by column chromatography.
性能测试Performance Testing
所有实施例所得到的产品都通过核磁共振谱和高分辨质谱得到了印证。具体如下：The products obtained in all examples have been confirmed by nuclear magnetic resonance spectrum and high-resolution mass spectrum. details as follows:
实施例1-4核磁及高分辨：1H NMR(400MHz,CDCl3)δ7.38-7.29(m,5H),5.11(s,2H),2.35(tt,J＝11.4,3.6Hz,1H),1.95-1.91(m,2H),1.77-1.73(m,2H),1.65-1.62(m,1H),1.51-1.41(m,2H),1.33-1.16(m,3H).13C NMR(101MHz,CDCl3)δ175.9,136.3,128.5,128.0,127.9,65.9,43.2,29.0,25.7,25.4.HRMS(EI)calcd for C14H18O2[M]+:218.1307；Found:218.1303。Example 1-4 NMR and high resolution: 1 H NMR (400MHz, CDCl 3 ) δ7.38-7.29 (m, 5H), 5.11 (s, 2H), 2.35 (tt, J=11.4, 3.6Hz, 1H) 13 C NMR ( 101MHz, CDCl 3 ) δ175.9, 136.3, 128.5, 128.0, 127.9, 65.9, 43.2, 29.0, 25.7, 25.4. HRMS (EI) calcd for C 14 H 18 O 2 [M] + : 218.1307; Found: 218.1303.
实施例5核磁及高分辨：1H NMR(400MHz,CDCl3)δ7.39-7.30(m,5H),5.12(s,2H),2.79(q,J＝8Hz,1H),1.95-1.86(m,2H),1.85-1.77(m,2H),1.75-1.65(m,2H),1.61-1.53(m,2H).13CNMR(101MHz,CDCl3)δ176.6,136.3,128.5,128.0,128.0,66.0,43.8,30.0,25.8.HRMS(EI)calcd for C13H16O2[M]+:204.1150；Found:204.1149。Example 5 NMR and high resolution: 1 H NMR (400MHz, CDCl 3 ) δ7.39-7.30 (m, 5H), 5.12 (s, 2H), 2.79 (q, J=8Hz, 1H), 1.95-1.86 ( m,2H),1.85-1.77(m,2H),1.75-1.65(m,2H),1.61-1.53(m,2H). 13 CNMR(101MHz,CDCl 3 )δ176.6,136.3,128.5,128.0,128.0, 66.0, 43.8, 30.0, 25.8. HRMS (EI) calcd for C 13 H 16 O 2 [M] + : 204.1150; Found: 204.1149.
实施例6核磁及高分辨：1H NMR(400MHz,CDCl3)δ7.32-7.30(m,1H),7.25-7.18(m,3H),5.11(s,2H),2.39-2.31(m,4H),1.94-1.91(m,2H),1.77-1.73(m,2H),1.65-1.63(m,1H),1.50-1.41(m,2H),1.32-1.16(m,3H).13C NMR(101MHz,CDCl3)δ175.9,136.9,134.1,130.3,129.0,128.3,125.9,66.4,43.2,29.0,25.7,25.4,18.9.HRMS(EI)calcd for C15H20O2[M]+:232.1463；Found:232.1459。Example 6 NMR and high resolution: 1 H NMR (400MHz, CDCl 3 ) δ7.32-7.30 (m, 1H), 7.25-7.18 (m, 3H), 5.11 (s, 2H), 2.39-2.31 (m, 13C NMR(101MHz,CDCl 3 )δ175.9,136.9,134.1,130.3,129.0,128.3,125.9,66.4,43.2,29.0,25.7,25.4,18.9.HRMS(EI)calcd for C 15 H 20 O 2 [M] + : 232.1463; Found: 232.1459.
实施例7核磁及高分辨：1H NMR(400MHz,CDCl3)δ7.25(m,1H),7.15-7.12(m,3H),5.07(s,2H),2.39-2.31(m,4H),1.95-1.91(m,2H),1.77-1.73(m,2H),1.65-1.62(m,1H),1.51-1.41(m,2H),1.32-1.16(m,3H).13C NMR(101MHz,CDCl3)δ176.0,138.1,136.1,128.8,128.7,128.4,125.0,65.9,43.2,29.0,25.7,25.4,21.4.HRMS(EI)calcd for C15H20O2[M]+:232.1463；Found:232.1465。Example 7 NMR and high resolution: 1 H NMR (400MHz, CDCl 3 ) δ7.25 (m, 1H), 7.15-7.12 (m, 3H), 5.07 (s, 2H), 2.39-2.31 (m, 4H) 13 C NMR ( 101MHz, CDCl 3 ) δ176.0, 138.1, 136.1, 128.8, 128.7, 128.4, 125.0, 65.9, 43.2, 29.0, 25.7, 25.4, 21.4.HRMS(EI) calcd for C 15 H 20 O 2 [M] + : 232.1463; Found: 232.1465.
实施例8核磁及高分辨：1H NMR(400MHz,CDCl3)δ7.24(d,J＝8.0Hz,2H),7.16(d,J＝7.6Hz,2H),5.06(s,2H),2.37-2.30(m,4H),1.94-1.90(m,2H),1.76-1.72(m,2H),1.65-1.62(m,1H),1.50-1.40(m,2H),1.32-1.15(m,3H).13C NMR(101MHz,CDCl3)δ176.0,137.9,133.2,129.2,128.1,65.8,43.2,29.0,25.7,25.4,21.2.HRMS(EI)calcd for C15H20O2[M]+:232.1463；Found:232.1461。Example 8 NMR and high resolution: 1 H NMR (400MHz, CDCl 3 ) δ7.24 (d, J = 8.0Hz, 2H), 7.16 (d, J = 7.6Hz, 2H), 5.06 (s, 2H), 2.37-2.30(m,4H),1.94-1.90(m,2H),1.76-1.72(m,2H),1.65-1.62(m,1H),1.50-1.40(m,2H),1.32-1.15(m ,3H) .13 C NMR(101MHz,CDCl 3 )δ176.0,137.9,133.2,129.2,128.1,65.8,43.2,29.0,25.7,25.4,21.2.HRMS(EI)calcd for C 15 H 20 O 2 [M] + :232.1463; Found: 232.1461.
实施例9核磁及高分辨：1H NMR(400MHz,CDCl3)δ7.28(d,J＝8.4Hz,2H),6.88(d,J＝8.8Hz,2H),5.04(s,2H),3.80(s,3H),2.32(tt,J＝11.2,3.6Hz,1H),1.92-1.89(m,2H),1.76-1.72(m,2H),1.64-1.62(m,1H),1.49-1.39(m,2H),1.31-1.15(m,3H).13C NMR(101MHz,CDCl3)δ176.0,159.4,129.8,128.4,113.8,65.7,55.2,43.2,29.0,25.7,25.4.HRMS(EI)calcd for C15H20O3[M]+:248.1412；Found:248.1407。Example 9 NMR and high resolution: 1 H NMR (400MHz, CDCl 3 ) δ7.28(d, J=8.4Hz, 2H), 6.88(d, J=8.8Hz, 2H), 5.04(s, 2H), 3.80(s,3H),2.32(tt,J＝11.2,3.6Hz,1H),1.92-1.89(m,2H),1.76-1.72(m,2H),1.64-1.62(m,1H),1.49- 1.39(m,2H),1.31-1.15(m,3H). 13 C NMR(101MHz,CDCl 3 )δ176.0,159.4,129.8,128.4,113.8,65.7,55.2,43.2,29.0,25.7,25.4.HRMS(EI ) calcd for C 15 H 20 O 3 [M] + : 248.1412; Found: 248.1407.
实施例10核磁及高分辨：1H NMR(400MHz,CDCl3)δ7.35-7.30(m,2H),7.07-7.01(m,2H),5.07(s,2H),2.34(tt,J＝11.2,3.6Hz,1H),1.94-1.90(m,2H),1.77-1.73(m,2H),1.66-1.62(m,1H),1.49-1.40(m,2H),1.33-1.16(m,3H).13C NMR(101MHz,CDCl3)δ175.9,162.5(d,JC-F＝247.5Hz)132.1(d,JC-F＝3.0Hz),129.9(d,JC-F＝8.1Hz),115.4(d,JC-F＝22.2Hz),65.2,43.1,28.9,25.7,25.4.19F NMR(377MHz,CDCl3)δ-114.0.HRMS(EI)calcd for C14H17FO2[M]+:236.1213；Found:236.1216。Example 10 NMR and high resolution: 1 H NMR (400MHz, CDCl 3 ) δ7.35-7.30(m, 2H), 7.07-7.01(m, 2H), 5.07(s, 2H), 2.34(tt, J= 11.2,3.6Hz,1H),1.94-1.90(m,2H),1.77-1.73(m,2H),1.66-1.62(m,1H),1.49-1.40(m,2H),1.33-1.16(m, 3H). 13 C NMR (101MHz, CDCl 3 ) δ175.9, 162.5 (d, J CF = 247.5Hz), 132.1 (d, J CF = 3.0Hz), 129.9 (d, J CF = 8.1Hz), 115.4 (d, J CF =22.2Hz), 65.2, 43.1, 28.9, 25.7, 25.4. 19 F NMR (377MHz, CDCl 3 ) δ-114.0.HRMS (EI) calcd for C 14 H 17 FO 2 [M] + :236.1213; Found :236.1216.
实施例11核磁及高分辨：1H NMR(400MHz,CDCl3)δ7.33(d,J＝8.4Hz,2H),7.27(d,J＝9.2Hz,2H),5.06(s,2H),2.34(tt,J＝11.2,3.6Hz,1H),1.94-1.90(m,2H),1.77-1.72(m,2H),1.66-1.61(m,1H),1.50-1.40(m,2H),1.33-1.16(m,3H).13C NMR(101MHz,CDCl3)δ175.7,134.8,133.9,129.3,128.7,65.0,43.1,29.0,25.7,25.4.HRMS(EI)calcd for C14H17ClO2[M]+:252.0917；Found:252.0921。Example 11 NMR and high resolution: 1 H NMR (400MHz, CDCl 3 ) δ7.33 (d, J = 8.4Hz, 2H), 7.27 (d, J = 9.2Hz, 2H), 5.06 (s, 2H), 2.34(tt,J＝11.2,3.6Hz,1H),1.94-1.90(m,2H),1.77-1.72(m,2H),1.66-1.61(m,1H),1.50-1.40(m,2H), 1.33-1.16(m,3H) .13 C NMR(101MHz,CDCl 3 )δ175.7,134.8,133.9,129.3,128.7,65.0,43.1,29.0,25.7,25.4.HRMS(EI)calcd for C 14 H 17 ClO 2 [M] + :252.0917; Found: 252.0921.
实施例12核磁及高分辨：1H NMR(400MHz,CDCl3)δ7.48(d,J＝8.4Hz,2H),7.22(d,J＝8.4Hz,2H),5.05(s,2H),2.34(tt,J＝11.4,3.6Hz,1H),1.94-1.90(m,2H),1.77-1.72(m,2H),1.66-1.61(m,1H),1.50-1.40(m,2H),1.33-1.16(m,3H).13C NMR(101MHz,CDCl3)δ175.7,135.3,131.6,129.6,122.0,65.0,43.1,28.9,25.7,25.4.HRMS(EI)calcd for C14H17BrO2[M]+:296.0412；Found:296.0417。Example 12 NMR and high resolution: 1 H NMR (400MHz, CDCl 3 ) δ7.48(d, J=8.4Hz, 2H), 7.22(d, J=8.4Hz, 2H), 5.05(s, 2H), 2.34(tt,J＝11.4,3.6Hz,1H),1.94-1.90(m,2H),1.77-1.72(m,2H),1.66-1.61(m,1H),1.50-1.40(m,2H), 1.33-1.16(m,3H) .13 C NMR(101MHz,CDCl 3 )δ175.7,135.3,131.6,129.6,122.0,65.0,43.1,28.9,25.7,25.4.HRMS(EI)calcd for C 14 H 17 BrO 2 [M] + :296.0412; Found: 296.0417.
实施例13核磁及高分辨：1H NMR(400MHz,CDCl3)δ7.62(d,J＝8.0Hz,2H),7.46(d,J＝8.0Hz,2H),5.16(s,2H),2.38(tt,J＝11.2,3.6Hz,1H),1.96-1.92(m,2H),1.79-1.75(m,2H),1.67-1.63(m,1H),1.52-1.42(m,2H),1.34-1.17(m,3H).13C NMR(101MHz,CDCl3)δ175.7,140.3,130.2(q,JC-F＝32.3Hz),127.9,125.5(q,JC-F＝4.0Hz),124.0(q,JC-F＝272.7Hz),64.9,43.1,29.0,25.7,25.4.19F NMR(377MHz,CDCl3)δ-62.6.HRMS(EI)calcd for C15H17F3O2[M]+:286.1181；Found:286.1180。Example 13 NMR and high resolution: 1 H NMR (400MHz, CDCl 3 ) δ7.62 (d, J = 8.0Hz, 2H), 7.46 (d, J = 8.0Hz, 2H), 5.16 (s, 2H), 2.38(tt,J＝11.2,3.6Hz,1H),1.96-1.92(m,2H),1.79-1.75(m,2H),1.67-1.63(m,1H),1.52-1.42(m,2H), 1.34-1.17(m,3H) .13 C NMR(101MHz,CDCl 3 )δ175.7,140.3,130.2(q,J CF ＝32.3Hz),127.9,125.5(q,J CF ＝4.0Hz),124.0(q, J CF ＝272.7Hz), 64.9, 43.1, 29.0, 25.7, 25.4. 19 F NMR (377MHz, CDCl 3 ) δ-62.6. HRMS (EI) calcd for C 15 H 17 F 3 O 2 [M] + :286.1181 ;Found: 286.1180.
实施例14核磁及高分辨：1H NMR(400MHz,CDCl3)δ7.59-7.57(m,4H),7.45-7.40(m,4H),7.35(tt,J＝7.2,1.2Hz,1H),5.14(s,2H),2.37(tt,J＝11.2,3.6Hz,1H),1.97-1.93(m,2H),1.78-1.74(m,2H),1.66-1.61(m,1H),1.53-1.43(m,2H),1.33-1.17(m,3H).13C NMR(101MHz,CDCl3)δ175.9,141.0,140.6,135.3,128.7,128.4,127.4,127.2,127.1,65.6,43.2,29.0,25.7,25.4.HRMS(EI)calcd for C20H22O2[M]+:294.1620；Found:294.1617。Example 14 NMR and high resolution: 1 H NMR (400MHz, CDCl 3 ) δ7.59-7.57 (m, 4H), 7.45-7.40 (m, 4H), 7.35 (tt, J=7.2, 1.2Hz, 1H) ,5.14(s,2H),2.37(tt,J=11.2,3.6Hz,1H),1.97-1.93(m,2H),1.78-1.74(m,2H),1.66-1.61(m,1H),1.53 -1.43(m,2H),1.33-1.17(m,3H). 13 C NMR(101MHz,CDCl 3 )δ175.9,141.0,140.6,135.3,128.7,128.4,127.4,127.2,127.1,65.6,43.2,29.0, 25.7, 25.4. HRMS (EI) calcd for C 20 H 22 O 2 [M] + : 294.1620; Found: 294.1617.
实施例15核磁及高分辨：1H NMR(400MHz,CDCl3)δ8.03(d,J＝8.4Hz,2H),7.40(d,J＝8.4Hz,2H),5.16(s,2H),3.92(s,3H),2.38(tt,J＝11.4,3.6Hz,1H),1.96-1.92(m,2H),1.78-1.74(m,2H),1.67-1.63(m,2H),1.52-1.42(m,2H),1.34-1.17(m,3H).13C NMR(101MHz,CDCl3)δ175.7,166.7,141.4,129.8,129.7,127.4,65.1,52.1,43.1,28.9,25.7,25.4.HRMS(EI)calcd forC16H20O4[M]+:276.1362；Found:276.1363。Example 15 NMR and high resolution: 1 H NMR (400MHz, CDCl 3 ) δ8.03 (d, J = 8.4Hz, 2H), 7.40 (d, J = 8.4Hz, 2H), 5.16 (s, 2H), 3.92(s,3H),2.38(tt,J＝11.4,3.6Hz,1H),1.96-1.92(m,2H),1.78-1.74(m,2H),1.67-1.63(m,2H),1.52- HRMS _ (EI) calcd for C 16 H 20 O 4 [M] + : 276.1362; Found: 276.1363.
实施例16核磁及高分辨：1H NMR(400MHz,CDCl3)δ7.33(s,4H),5.10(s,4H),2.35(tt,J＝11.4,3.6Hz,2H),1.95-1.90(m,4H),1.77-1.73(m,4H),1.66-1.62(m,2H),1.51-1.41(m,4H),1.33-1.16(m,6H).13C NMR(101MHz,CDCl3)δ175.9,136.2,128.1,65.5,43.2,29.0,25.7,25.4.HRMS(ESI)calcd for C22H34NO4[M+[NH4]+]:376.2482；Found:376.2482。Example 16 NMR and high resolution: 1 H NMR (400MHz, CDCl 3 ) δ7.33 (s, 4H), 5.10 (s, 4H), 2.35 (tt, J=11.4, 3.6Hz, 2H), 1.95-1.90 (m,4H), 1.77-1.73(m,4H), 1.66-1.62(m,2H), 1.51-1.41(m,4H), 1.33-1.16(m,6H). 13 C NMR (101MHz, CDCl 3 )δ 175.9, 136.2, 128.1, 65.5, 43.2, 29.0, 25.7, 25.4. HRMS (ESI) calcd for C 22 H 34 NO 4 [M+[NH 4 ] + ]: 376.2482; Found: 376.2482.
实施例17核磁及高分辨：1H NMR(400MHz,CDCl3)δ7.84-7.80(m,4H),7.50-7.43(m,3H),5.26(s,2H),2.38(tt,J＝11.4,3.6Hz,2H),1.97-1.93(m,2H),1.77-1.73(m,2H),1.65-1.61(m,1H),1.53-1.43(m,2H),1.33-1.16(m,6H).13C NMR(101MHz,CDCl3)δ175.9,133.7,133.1,133.0,128.3,127.9,127.7,127.1,126.2,126.1,125.7,66.0,43.2,29.0,25.7,25.4.HRMS(EI)calcd for C18H20O2[M]+:268.1463；Found:268.1459。Example 17 NMR and high resolution: 1 H NMR (400MHz, CDCl 3 ) δ7.84-7.80 (m, 4H), 7.50-7.43 (m, 3H), 5.26 (s, 2H), 2.38 (tt, J= 11.4,3.6Hz,2H),1.97-1.93(m,2H),1.77-1.73(m,2H),1.65-1.61(m,1H),1.53-1.43(m,2H),1.33-1.16(m, 6H). 13 C NMR (101MHz, CDCl 3 ) δ175.9, 133.7, 133.1, 133.0, 128.3, 127.9, 127.7, 127.1, 126.2, 126.1, 125.7, 66.0, 43.2, 29.0, 25.7, 25.4. HRMS (EI) calcd for C 18 H 20 O 2 [M] + : 268.1463; Found: 268.1459.
实施例18核磁及高分辨：1H NMR(400MHz,CDCl3)δ7.98(d,J＝8Hz,1H),7.89-7.8(m,2H),7.57-7.49(m,3H),7.46-7.42(m,1H),5.55(s,2H),2.35(tt,J＝11.2,3.6Hz,2H),1.94-1.90(m,2H),1.75-1.70(m,2H),1.62-1.58(m,1H),1.51-1.41(m,2H),1.29-1.14(m,3H).13C NMR(101MHz,CDCl3)δ176.0,133.7,131.7,131.6,129.1,128.7,127.2,126.4,125.9,125.2,123.6,64.3,43.2,29.0,25.7,25.4.HRMS(EI)calcd for C18H20O2[M]+:268.1463；Found:268.1462。Example 18 NMR and high resolution: 1 H NMR (400MHz, CDCl 3 ) δ7.98 (d, J=8Hz, 1H), 7.89-7.8 (m, 2H), 7.57-7.49 (m, 3H), 7.46- 7.42(m,1H),5.55(s,2H),2.35(tt,J＝11.2,3.6Hz,2H),1.94-1.90(m,2H),1.75-1.70(m,2H),1.62-1.58( m,1H),1.51-1.41(m,2H),1.29-1.14(m,3H). 13 C NMR(101MHz,CDCl 3 )δ176.0,133.7,131.7,131.6,129.1,128.7,127.2,126.4,125.9, 125.2, 123.6, 64.3, 43.2, 29.0, 25.7, 25.4. HRMS (EI) calcd for C 18 H 20 O 2 [M] + : 268.1463; Found: 268.1462.
实施例19核磁及高分辨：1H NMR(400MHz,CDCl3)δ7.34(m,4H),7.31-7.26(m,1H),5.87(q,J＝6.8Hz,1H),2.32(tt,J＝11.2,3.6Hz,2H),1.95-1.88(m,2H),1.77-1.72(m,2H),1.65-1.61(m,1H),1.52(d,J＝6.8Hz,2H),1.47-1.37(m,2H),1.33-1.15(m,3H).13C NMR(101MHz,CDCl3)δ175.3,142.0,128.4,127.7,125.9,71.7,43.3,28.9,25.7,25.4,22.3.HRMS(EI)calcd for C15H20O2[M]+:232.1463；Found:232.1471。Example 19 NMR and high resolution: 1 H NMR (400MHz, CDCl 3 ) δ7.34(m, 4H), 7.31-7.26(m, 1H), 5.87(q, J=6.8Hz, 1H), 2.32(tt ,J=11.2,3.6Hz,2H),1.95-1.88(m,2H),1.77-1.72(m,2H),1.65-1.61(m,1H),1.52(d,J=6.8Hz,2H), HRMS _ (EI) calcd for C 15 H 20 O 2 [M] + : 232.1463; Found: 232.1471.
实施例20核磁及高分辨：1H NMR(400MHz,CDCl3)δ7.34(m,4H),7.31-7.26(m,1H),5.87(q,J＝6.8Hz,1H),2.32(tt,J＝11.4,3.6Hz,2H),1.95-1.88(m,2H),1.77-1.72(m,2H),1.65-1.62(m,1H),1.52(d,J＝6.4Hz,2H),1.47-1.37(m,2H),1.33-1.15(m,3H).13C NMR(101MHz,CDCl3)δ175.3,142.0,128.4,127.7,125.9,71.7,43.3,28.9,25.7,25.4,22.3.HRMS(EI)calcd for C15H20O2[M]+:232.1463；Found:232.1458。Example 20 NMR and high resolution: 1 H NMR (400MHz, CDCl 3 ) δ7.34(m, 4H), 7.31-7.26(m, 1H), 5.87(q, J=6.8Hz, 1H), 2.32(tt ,J=11.4,3.6Hz,2H),1.95-1.88(m,2H),1.77-1.72(m,2H),1.65-1.62(m,1H),1.52(d,J=6.4Hz,2H), ( EI) calcd for C 15 H 20 O 2 [M] + : 232.1463; Found: 232.1458.
实施例21核磁及高分辨：1H NMR(400MHz,CDCl3)δ7.34(m,4H),7.31-7.26(m,1H),5.87(q,J＝6.8Hz,1H),2.32(tt,J＝11.4,3.6Hz,2H),1.95-1.88(m,2H),1.77-1.72(m,2H),1.65-1.62(m,1H),1.52(d,J＝6.4Hz,2H),1.47-1.37(m,2H),1.33-1.15(m,3H).13C NMR(101MHz,CDCl3)δ175.3,142.0,128.4,127.7,125.9,71.7,43.3,28.9,25.7,25.4,22.3.HRMS(EI)calcd for C15H20O2[M]+:232.1463；Found:232.1470。Example 21 NMR and high resolution: 1 H NMR (400MHz, CDCl 3 ) δ7.34(m, 4H), 7.31-7.26(m, 1H), 5.87(q, J=6.8Hz, 1H), 2.32(tt ,J=11.4,3.6Hz,2H),1.95-1.88(m,2H),1.77-1.72(m,2H),1.65-1.62(m,1H),1.52(d,J=6.4Hz,2H), ( EI) calcd for C 15 H 20 O 2 [M] + : 232.1463; Found: 232.1470.
实施例22核磁及高分辨：1H NMR(400MHz,CDCl3)δ7.32-7.28(m,2H),7.24-7.21(m,3H),4.28(t,J＝7.0Hz,2H),2.93(t,J＝7.0Hz,2H),2.27(tt,J＝11.2,3.6Hz,1H),1.88-1.84(m,2H),1.75-1.71(m,2H),1.64-1.60(m,1H),1.45-1.36(m,2H),1.31-1.15(m,3H).13C NMR(101MHz,CDCl3)δ176.0,137.9,128.9,128.4,126.4,64.6,43.1,35.1,28.9,25.7,25.4.HRMS(EI)calcd forC15H20O2[M]+:232.1463；Found:232.1462。Example 22 NMR and high resolution: 1 H NMR (400MHz, CDCl 3 ) δ7.32-7.28 (m, 2H), 7.24-7.21 (m, 3H), 4.28 (t, J=7.0Hz, 2H), 2.93 (t,J=7.0Hz,2H),2.27(tt,J=11.2,3.6Hz,1H),1.88-1.84(m,2H),1.75-1.71(m,2H),1.64-1.60(m,1H ),1.45-1.36(m,2H),1.31-1.15(m,3H). 13 C NMR(101MHz,CDCl 3 )δ176.0,137.9,128.9,128.4,126.4,64.6,43.1,35.1,28.9,25.7,25.4 .HRMS(EI) calcd for C 15 H 20 O 2 [M] + : 232.1463; Found: 232.1462.
实施例23核磁及高分辨：1H NMR(400MHz,CDCl3)δ4.11(q,J＝7.2Hz,2H),2.28(tt,J＝11.4,3.6Hz,1H),1.92-1.88(m,2H),1.77-1.74(m,2H),1.66-1.61(m,1H),1.48-1.39(m,2H),1.33-1.17(m,6H).13C NMR(101MHz,CDCl3)δ176.1,60.0,43.2,29.0,25.7,25.4,14.2.HRMS(EI)calcd for C9H16O2[M]+:156.1150；Found:156.1154。Example 23 NMR and high resolution: 1 H NMR (400MHz, CDCl 3 ) δ4.11(q, J=7.2Hz, 2H), 2.28(tt, J=11.4, 3.6Hz, 1H), 1.92-1.88(m ,2H),1.77-1.74(m,2H),1.66-1.61(m,1H),1.48-1.39(m,2H),1.33-1.17(m,6H). 13 C NMR(101MHz,CDCl 3 )δ176 .1, 60.0, 43.2, 29.0, 25.7, 25.4, 14.2. HRMS (EI) calcd for C 9 H 16 O 2 [M] + : 156.1150; Found: 156.1154.
实施例24核磁及高分辨：1H NMR(400MHz,CDCl3)δ4.06(t,J＝6.8Hz,2H),2.28(tt,J＝11.2,3.6Hz,1H),1.92-1.88(m,2H),1.77-1.73(m,2H),1.66-1.57(m,3H),1.48-1.35(m,4H),1.33-1.17(m,3H),0.93(t,J＝7.4Hz,3H).13C NMR(101MHz,CDCl3)δ176.2,63.9,43.3,30.7,29.0,25.8,25.4,19.1,13.7.HRMS(EI)calcd for C11H20O2[M]+:184.1463；Found:184.1465。Example 24 NMR and high resolution: 1 H NMR (400MHz, CDCl 3 ) δ4.06(t, J=6.8Hz, 2H), 2.28(tt, J=11.2, 3.6Hz, 1H), 1.92-1.88(m ,2H),1.77-1.73(m,2H),1.66-1.57(m,3H),1.48-1.35(m,4H),1.33-1.17(m,3H),0.93(t,J＝7.4Hz,3H ). 13 C NMR (101MHz, CDCl 3 ) δ176.2, 63.9, 43.3, 30.7, 29.0, 25.8, 25.4, 19.1, 13.7. HRMS (EI) calcd for C 11 H 20 O 2 [M] + : 184.1463; Found: 184.1465.
所有实施例所使用的环烷烃化合物、醇化合物和产物以及分离收率如表1所示：表1环烷烃化合物与醇化合物的羰基化反应The cycloalkane compound, alcohol compound and product used in all embodiments and the separation yield are shown in Table 1: the carbonylation reaction of table 1 cycloalkane compound and alcohol compound
上述实施例为本发明较佳的实施方式，但本发明的实施方式并不受上述实施例的限制，其他的任何未背离本发明的精神实质与原理下所作的改变、修饰、替代、组合、简化，均应为等效的置换方式，都包含在本发明的保护范围之内。The above-mentioned embodiment is a preferred embodiment of the present invention, but the embodiment of the present invention is not limited by the above-mentioned embodiment, and any other changes, modifications, substitutions, combinations, Simplifications should be equivalent replacement methods, and all are included in the protection scope of the present invention.
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