CN106588644B - A kind of synthetic method of carboxylic acid ester compound - Google Patents
A kind of synthetic method of carboxylic acid ester compound Download PDFInfo
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- CN106588644B CN106588644B CN201611006903.6A CN201611006903A CN106588644B CN 106588644 B CN106588644 B CN 106588644B CN 201611006903 A CN201611006903 A CN 201611006903A CN 106588644 B CN106588644 B CN 106588644B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/39—Preparation of carboxylic acid esters by oxidation of groups which are precursors for the acid moiety of the ester
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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Abstract
The present invention provides a kind of synthetic method of ester type compound as shown in formula (1), formula (2) or formula (3), the method are as follows: aldehyde compound, sodium azide, tetrabutylammonium iodide and halogenated compound are dissolved in solvent, or aldehyde compound, sodium azide, tetrabutylammonium iodide are directly dissolved in halogenated compound, 1~12h is reacted at 90-100 DEG C, after reaction, reaction solution is post-treated obtains formula (1) compound represented.Reaction condition of the present invention is mild, participates in without strong acid and strong base and metal, and synthetic method is simple and efficient, yield is high, wide application range of substrates and the potentiality with amplification production, has biggish potential age deduction.
Description
(1) technical field
The present invention relates to a kind of synthetic methods of carboxylic acid ester compound.
(2) background technique
Carboxylate is a kind of important organic chemical industry's intermediate and pharmaceutical intermediate, most in research report in recent years
Researcher makees oxidative esterification catalyst using noble metal, expensive.The synthetic method of traditional ester type compound concentrates on carboxylic acid
It is prepared under strong acid or basic conditions with alcohol, but the use of strong acid and strong base is unfavorable for environmental protection and to production equipment requirement
Height, environmental protection pressure are big.Meanwhile such synthetic method is not suitable for the system of some pairs of acid or the sensitive special ester type compound of alkali
It is standby.Some researchers use homogeneous catalyst, have the advantages that high-activity high-selectivity in the reaction, but dosage is big, and
It is not easy to separate with product and reagent after reaction；Simultaneously there is also the residue problem of poisonous and harmful heavy metallic, it is constrained in work
Practical application in industry production.Therefore, in order to promote the development that further oxidative esterification is studied, using aldehyde as Material synthesis ester
Method is using very extensively in the synthesis of organic chemical industry's intermediate, and there are many routes that ester is generated by aldehyde, can be oxidized to carboxylic acid
It afterwards with alcohol direct esterification, or is converted to after carboxylate and is reacted with active alkyl halide etc., in recent years, with one step oxide ester of aldehyde and alcohol
It is combined to the concern that ester causes some scholars.
Carboxylate is a kind of important organic chemical industry's intermediate and pharmaceutical intermediate,
The main component of chocolate
The main component of honey
The main component of vanilla
The main component of caramel
The main component of plastic plasticizer
Therefore, the present invention uses oxidant, reacts in the case where relatively mild condition passes through, and explores an easy conjunction
At the route of carboxylic acid ester compound, reaction equation is as follows:
(3) summary of the invention
The purpose of the present invention is to provide a kind of synthetic methods of carboxylic acid ester compound.
To achieve the above object, the present invention adopts the following technical scheme:
The method of asymmetric synthesis of one kind carboxylic acid ester compound as shown in formula (1), formula (2) or formula (3), the conjunction
It is specifically carried out as follows at method:
Aldehyde compound, tetrabutylammonium iodide, sodium azide, oxidant tert-butyl hydroperoxide and halogenated alkane are dissolved in
In organic solvent, 1~12h is reacted at 90 DEG C, after reaction, reaction solution is post-treated to obtain formula (1), formula (2) or formula (3)
Compound represented；The aldehyde, tetrabutylammonium iodide, sodium azide, tert-butyl hydroperoxide and halogenated alkane substance amount
The ratio between be 1:0.1~0.2:2-3:1.5~6:2~5；The C atom number of the halogenated alkane is 1~5；
Wherein: in formula (1), formula (2) or formula (3), the R1For C1~4Alkyl, methoxyl group, nitro, phenyl, naphthalene, halogen
Or trifluoromethyl；The R2For C1~4The phenyl that alkyl, benzyl, phenyl or alkyl, halogen atom replace；The R3For H, methyl, second
Base or chain-like alkyl；The R4For C1~4The phenyl that alkyl, benzyl, phenyl or alkyl, halogen atom replace；The aldehydes chemical combination
Object is the aldehyde with aromatics property.
Further, the aldehyde compound are as follows: P-methoxybenzal-dehyde, m-methoxybenzaldehyde, O-methoxy benzene first
Aldehyde, p-tolyl aldehyde, tolyl aldehyde, o-tolualdehyde, paranitrobenzaldehyde, m-nitrobenzaldehyde, ortho-nitrophenyl
Formaldehyde, 2- naphthaldehyde, furfural, 5- methylfuran aldehyde, 2 thiophene carboxaldehyde or o-phthalaldehyde.
Further, the halogenated alkane are as follows: methylene chloride, carbon tetrachloride, benzyl chloride, cylite, iodomethane, dibromo second
Alkane, 1,2- dichloroethanes, bromobutane, allyl chloride, bromopropyl bromine or allyl iodide.
Further, the organic solvent is toluene, tetrahydrofuran, n,N-Dimethylformamide or benzene.
Further, the volumetric usage of the organic solvent is calculated as 0.2~2mL/mmol with the amount of the substance of aldehyde.
Further, the method for the reaction solution post-processing are as follows: after reaction, reaction solution is extracted with dichloromethane, extraction
The dry vacuum removal of liquid is taken, after solvent under reduced pressure concentration, gained concentrate carries out column chromatography for separation with 200~300 mesh silica gel, elution
Agent is the mixed liquor of ethyl acetate and petroleum ether volume ratio 1:20, collects the eluent containing target compound, and concentrate drying obtains
Formula (1), formula (2) or formula (3) compound represented.
More specifically, the ester type compound is one of following: 4- methoxy benzoic acid benzyl ester, 4- methoxybenzene first
Sour methyl esters, 4- methoxy ethylbenzoate, 4- methoxy benzoic acid butyl ester, 4- methoxy benzoic acid allyl ester, 4- methoxybenzene
Formic acid chloroethene ester, 4- ((4- methoxy-benzyl) oxygroup) benzyl -4- methoxyl methyl benzoate, 4- methoxy benzoic acid tribromo first
Ester, 2- methyl benzoic acid chloromethyl ester, 3- methyl benzoic acid chloromethyl ester, 4- methyl benzoic acid chloromethyl ester, 2- nitrobenzoic acid chloromethane
Ester, 3- nitrobenzoic acid chloromethyl ester, 4- nitrobenzoic acid chloromethyl ester, O-Anisic Acid chloromethyl ester, 3- methoxy benzoic acid
Chloromethyl ester, 4- methoxy benzoic acid chloromethyl ester, 4- ethyl benzoate chloromethyl ester, 2- thiophenic acid chloromethyl ester, di-2-ethylhexylphosphine oxide (thiophene
Pheno -2- carboxylate), 2- naphthoic acid chloromethyl ester, 2- furancarboxylic acid chloromethyl ester, 5- methylfuran -2- monochlorome-thylchloroformate or tert-butyl
(chloromethyl) phthalic acid.
The carboxylic acid ester compound that the present invention is prepared has antibiotic property, pesticidal, antitumor and arrhythmia etc.
Bioactivity can be used as the important as precursors of drug.
Compared with prior art, beneficial effect of the present invention is mainly reflected in:
(1) ester type compound of the present invention has chirality, is a kind of critically important medicine intermediate, is widely present
In medicine and natural products skeleton, space is had a wide range of applications.
(2) synthetic method of the invention, easy to operate, reaction condition is mild, shows good response characteristic, and reaction is received
Rate is high.
(3) use of traditional esterifications reaction strong acid or basic conditions is avoided in synthetic method of the invention, simultaneously also
Environmentally friendly without the participation of poisonous and harmful metal, equipment requirement is lower, and production environmental protection pressure is smaller.
(4) inventive substrate is applied widely, works well for aromatic aldehyde, heteroaromatic aldehyde, complicated aromatic aldehyde；Together
When various chain halogenated hydrocarbons, cyclic halo hydrocarbon, compound fragrant hydrocarbon can realize outstanding yield, have wide range of applications, have
There is extraordinary economic value.
(5) synthesis material of the invention is cheap and easily-available, and it is more complicated with special bioactivity esters to be suitable for structure
The efficient preparation of compound, is with a wide range of applications, and is effective supplement of traditional esterifications reaction.
Further, a kind of preparation method of the carboxylic acid ester compound as shown in formula (1), formula (2) or formula (3), the side
Method can also carry out as follows:
Tetrabutylammonium iodide, sodium azide and oxidant tert-butyl hydroperoxide are added into aldehyde compound, is dissolved in halogen
For in alkane, 1~12h is reacted at 90~100 DEG C, after reaction, reaction solution is post-treated to obtain formula (1), formula (2) or formula
(3) compound represented；The aldehyde compound, tetrabutylammonium iodide, sodium azide and tert-butyl hydroperoxide substance
The ratio between amount is 1:0.1~0.2:2~3:1.5~6；The C atom number of the halogenated alkane is 1~5；
Wherein: in formula (1), formula (2) or formula (3), the R1For C1~4Alkyl, methoxyl group, nitro, phenyl, naphthalene, halogen
Or trifluoromethyl；The R2For C1~4The phenyl that alkyl, benzyl, phenyl or alkyl, halogen atom replace；The R3For H, methyl, second
Base or other chain-like alkyls；The R4For C1~4The phenyl that alkyl, benzyl, phenyl or alkyl, halogen atom replace；The aldehydes
Compound is the aldehyde with aromatics property.
Further, the aldehyde compound are as follows: P-methoxybenzal-dehyde, m-methoxybenzaldehyde, O-methoxy benzene first
Aldehyde, p-tolyl aldehyde, tolyl aldehyde, o-tolualdehyde, paranitrobenzaldehyde, m-nitrobenzaldehyde, ortho-nitrophenyl
Formaldehyde, 2- naphthaldehyde, furfural, 5- methylfuran aldehyde, 2 thiophene carboxaldehyde or o-phthalaldehyde.
Further, the halogenated alkane are as follows: methylene chloride, chloroform, carbon tetrachloride, benzyl chloride, cylite, iodine first
Alkane, bromoethane, 1,2- dichloroethanes, bromobutane, allyl chloride, bromopropyl bromine or allyl iodide.
Further, the method for the reaction solution post-processing are as follows: after reaction, reaction solution is extracted with dichloromethane, extraction
The dry vacuum removal of liquid is taken, after solvent under reduced pressure concentration, gained concentrate carries out column chromatography for separation with 200~300 mesh silica gel, elution
Agent is the mixed liquor of ethyl acetate and petroleum ether volume ratio 1:20, collects the eluent containing target compound, and concentrate drying obtains
Formula (1), formula (2) or formula (3) compound represented.
More specifically, the ester type compound is one of following: 4- methoxy benzoic acid benzyl ester, 4- methoxybenzene first
Sour methyl esters, 4- methoxy ethylbenzoate, 4- methoxy benzoic acid butyl ester, 4- methoxy benzoic acid allyl ester, 4- methoxybenzene
Formic acid chloroethene ester, 2- methyl benzoic acid chloromethyl ester, 3- methyl benzoic acid chloromethyl ester, 4- methyl benzoic acid chloromethyl ester, 2- nitrobenzene
Monochlorome-thylchloroformate, 3- nitrobenzoic acid chloromethyl ester, 4- nitrobenzoic acid chloromethyl ester, O-Anisic Acid chloromethyl ester, 3- methoxy
Yl benzoic acid chloromethyl ester, 4- methoxy benzoic acid chloromethyl ester, 4- ethyl benzoate chloromethyl ester, 2- thiophenic acid chloromethyl ester, methylene
Base bis- (thiophene-2-carboxylic acid esters), 2- naphthoic acid chloromethyl ester, 2- furancarboxylic acid chloromethyl ester, 5- methylfuran -2- monochlorome-thylchloroformate or
Tert-butyl (chloromethyl) phthalic acid.
The carboxylic acid ester compound that the present invention is prepared has antibiotic property, pesticidal, antitumor and arrhythmia etc.
Bioactivity can be used as the important as precursors of drug.
Compared with prior art, beneficial effect of the present invention is mainly reflected in:
(1) carboxylic acid ester compound of the present invention has chirality, is a kind of critically important medicine intermediate, extensively
It is present in medicine and natural products skeleton, has a wide range of applications space.
(2) synthetic method of the invention, easy to operate, reaction condition is mild, shows good response characteristic, and reaction is received
Rate is high.
(3) use of traditional esterifications reaction strong acid or basic conditions is avoided in synthetic method of the invention, simultaneously also
Environmentally friendly without the participation of poisonous and harmful metal, equipment requirement is lower, and production environmental protection pressure is smaller.
(4) inventive substrate is applied widely, works well for aromatic aldehyde, heteroaromatic aldehyde, complicated aromatic aldehyde；Together
When various chain halogenated hydrocarbons, cyclic halo hydrocarbon, compound fragrant hydrocarbon can realize outstanding yield, have wide range of applications, have
There is extraordinary economic value.
(5) synthesis material of the invention is cheap and easily-available, and it is more complicated with special bioactivity esters to be suitable for structure
The efficient preparation of compound, is with a wide range of applications, and is effective supplement of traditional esterifications reaction.
(4) specific embodiment
Below by specific embodiment, the invention will be further described, but protection scope of the present invention is not limited in
This.
The preparation of embodiment 1:4- methoxy benzoic acid benzyl ester
Clean 15mL reaction under high pressure bottle is taken, P-methoxybenzal-dehyde (74.8mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and benzyl chloride (139.24mg, 1.1mmol), solvent toluene (1.0mL), is added small magneton, after 100 DEG C of reaction 2h,
Methylene chloride (3 × 10mL) extraction, organic phase depressurizes precipitation, with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, 300
Mesh column chromatography silica gel is filler, the target product (118.50mg, yield 89%) that column chromatography for separation purifies.
1HNMR(500MHz,CDCl3): δ=8.04-8.02 (m, 2H), 7.44-7.43 (m, 2H), 7.39-7.36 (m,
2H),7.34-7.31(ddd,1H),5.33(s,2H),3.83(s,3H)；13CNMR(125MHz,CDCl3): δ=166.21,
163.47,136.34,131.77,128.59,128.16,128.12,122.57,113.65,66.41,55.43ppm；
The preparation of embodiment 2:4- methoxyl methyl benzoate
Clean 15mL reaction under high pressure bottle is taken, P-methoxybenzal-dehyde (74.8mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and iodomethane (156.15mg, 1.1mmol) solvent toluene (1.0mL), it is added small magneton, after 90 DEG C of reaction 2h,
Methylene chloride (3 × 10mL) extraction, organic phase depressurizes precipitation, with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, 300
Mesh column chromatography silica gel is filler, the target product (76.71mg, yield 84%) that column chromatography for separation purifies.
1H NMR(500MHz,CDCl3): δ=8.00-7.98 (d, 2H), 6.92-6.91 (d, 2H), 3.88 (s, 3H),
3.86(s,3H)；13C NMR(125MHz,CDCl3): δ=166.88,163.33,131.51,122.61,113.60,55.41,
51.86ppm.
The preparation of embodiment 3:4- methoxy ethylbenzoate
Clean 15mL reaction under high pressure bottle is taken, P-methoxybenzal-dehyde (74.8mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and bromoethane (119.86mg, 1.1mmol), solvent toluene (1.0mL), small magneton, 90 DEG C of reaction 2h are added
Afterwards, methylene chloride (3 × 10mL) extracts, and organic phase depressurizes precipitation, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent,
300 mesh column chromatography silica gels are filler, the target product (83.19mg, yield 84%) that column chromatography for separation purifies.
1H NMR(500MHz,CDCl3): δ=8.01-7.99 (d, 2H), 6.92-6.90 (d, 2H), 4.37-4.32 (q,
2H),3.85(s,3H),1.39-1.36(t,1H)；13C NMR(125MHz,CDCl3): δ=166.41,163.25,131.53,
125.92,122.96,114.01,113.54,60.63,55.40,14.38ppm.
The preparation of embodiment 4:4- methoxy benzoic acid butyl ester
Clean 15mL reaction under high pressure bottle is taken, P-methoxybenzal-dehyde (74.8mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and bromobutane (150.72mg, 1.1mmol), solvent toluene (1.0mL), small magneton, 90 DEG C of reaction 2h are added
Afterwards, methylene chloride (3 × 10mL) extracts, and organic phase depressurizes precipitation, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent,
300 mesh column chromatography silica gels are filler, the target product (97.29mg, yield 85%) that column chromatography for separation purifies.
1H NMR(500MHz,CDCl3): δ=8.00-7.99 (d, 2H), 6.92-6.90 (d, 2H), 4.30-4.28 (t,
2H),3.85(s,3H),1.75-1.71(m,2H),1.49-1.45(m,2H),0.99-0.96(t,3H)；13C NMR(125MHz,
CDCl3): δ=166.44,163.25,131.52,125.90,122.98,113.54,77.31,77.06,76 .81,64.52,
55.39,30.84,19.29,13.77ppm.
The preparation of embodiment 5:4- methoxy benzoic acid allyl ester
Clean 15mL reaction under high pressure bottle is taken, P-methoxybenzal-dehyde (74.8mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and allyl chloride (84.17mg, 1.1mmol), solvent toluene (1.0mL), small magneton, 90 DEG C of reaction 5h are added
Afterwards, methylene chloride (3 × 10mL) extracts, and organic phase depressurizes precipitation, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent,
300 mesh column chromatography silica gels are filler, the target product (84.52mg, yield 84%) that column chromatography for separation purifies.
1H NMR(500MHz,CDCl3): δ=7.96-7.94 (d, 2H), 6.86-6.84 (d, 2H), 6.00-5.93 (m,
1H),5.35-5.31(ddd,1H),5.22-5.19(dd,1H),4.74-4.72(dt,2H),3.79(s,3H)；13C NMR
(125MHz,CDCl3): δ=165.01,162.38,131.46,130.65,121.56,116.95,112.60,64.25,
54.41ppm；
The preparation of embodiment 6:4- methoxy benzoic acid allyl ester
Clean 15mL reaction under high pressure bottle is taken, P-methoxybenzal-dehyde (74.8mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and small magneton, 90 DEG C of reaction 5h are added in allyl bromide, bromoallylene (116.53mg, 1.1mmol), solvent toluene (1.0mL)
Afterwards, methylene chloride (3 × 10mL) extracts, and organic phase depressurizes precipitation, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent,
300 mesh column chromatography silica gels are filler, the target product (84.52mg, yield 84%) that column chromatography for separation purifies.
1H NMR (500MHz, CDCl3): δ=7.96-7.94 (d, 2H), 6.86-6.84 (d, 2H), 6.00-5.93 (m,
1H),5.35-5.31(ddd,1H),5.22-5.19(dd,1H),4.74-4.72(dt, 2H),3.79(s,3H)；13C NMR
(125MHz, CDCl3): δ=165.01,162.38,131.46,130.65,121.56,116.95,112.60,64.25,
54.41ppm
The preparation of embodiment 7:4- methoxy benzoic acid allyl ester
Clean 15mL reaction under high pressure bottle is taken, P-methoxybenzal-dehyde (74.8mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and small magneton, 90 DEG C of reaction 5h are added in allyl iodide (169.32mg, 1.1mmol), solvent toluene (1.0mL)
Afterwards, methylene chloride (3 × 10mL) extracts, and organic phase depressurizes precipitation, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent,
300 mesh column chromatography silica gels are filler, the target product (80.49mg, yield 80%) that column chromatography for separation purifies.
1H NMR (500MHz, CDCl3): δ=7.96-7.94 (d, 2H), 6.86-6.84 (d, 2H), 6.00-5.93 (m,
1H),5.35-5.31(ddd,1H),5.22-5.19(dd,1H),4.74-4.72(dt,2H),3.79(s,3H)；13C NMR
(125MHz, CDCl3): δ=165.01,162.38,131.46,130.65,121.56,116.95,112.60,64.25,
54.41ppm
The preparation of embodiment 8:4- methoxy benzoic acid chloroethene ester
Clean 15mL reaction under high pressure bottle is taken, P-methoxybenzal-dehyde (74.8mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and 1, small magneton is added in 2- dichloroethanes (108.75mg, 1.1mmol), solvent toluene (1.0mL), and 90 DEG C anti-
After answering 6h, methylene chloride (3 × 10mL) extraction, organic phase depressurizes precipitation, is elution with ethyl acetate: petroleum ether=1:30 solvent
Agent, 300 mesh column chromatography silica gels are filler, the target product (100.06mg, yield 85%) that column chromatography for separation purifies.
1H NMR(500MHz,CDCl3): δ=8.03-8.01 (d, 2H), 6.94-6.92 (d, 2H), 4.55-4.53 (t,
2H),3.87(s,3H),3.82-3.79(t,3H)；13C NMR(125MHz,CDCl3): δ=165.92,163.63,131.82,
125.93,122.01,113.71,64.19,55.46,41.81ppm.
The preparation of embodiment 9:4- ((4- methoxy-benzyl) oxygroup) benzyl -4- methoxyl methyl benzoate
Clean 15mL reaction under high pressure bottle is taken, P-methoxybenzal-dehyde (74.8mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and to bromobenzyl bromine (136.33mg, 0.55mmol), small magneton, 90 DEG C of reactions are added in solvent toluene (1.0mL)
After 6h, methylene chloride (3 × 10mL) extraction, organic phase depressurizes precipitation, is elution with ethyl acetate: petroleum ether=1:30 solvent
Agent, 300 mesh column chromatography silica gels are filler, the target product (170.38mg, yield 79%) that column chromatography for separation purifies.
1H NMR(500MHz,CDCl3): δ=8.21-8.19 (d, 2H), 8.02-8.00 (d, 2H), 7.51-7.49 (d,
2H),7.32-7.30(d,2H),6.96-6.91(m,4H),5.28(s,2H),3.90(s,3H),3.86(s,3H)；13C NMR
(125MHz,CDCl3): δ=166.06,164.60,163.56,135.35,132.00,131.75,131.72,129.80,
125.93,122.28,114.02,113.69,65.60,55.97,55.46ppm；
The preparation of embodiment 10:4- methoxy benzoic acid tribromo methyl esters
Clean 15mL reaction under high pressure bottle is taken, P-methoxybenzal-dehyde (74.8mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and small magneton, 90 DEG C of reaction 3h are added in carbon tetrabromide (356.04mg, 1.10mmol), solvent toluene (1.0mL)
Afterwards, methylene chloride (3 × 10mL) extracts, and organic phase depressurizes precipitation, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent,
300 mesh column chromatography silica gels are filler, the target product (173.71mg, yield 75%) that column chromatography for separation purifies.
1H NMR(500MHz,CDCl3): δ=7.94-7.92 (d, 2H), 6.90-6.88 (d, 2H), 7.51-7.49 (d,
2H),3.77(s,3H)；13C NMR(125MHz,CDCl3): δ=164.61,161.93,130.35,112.36,79.51,
54.38,27.24ppm.
The preparation of embodiment 11:2- methyl benzoic acid chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, 2- tolyl aldehyde (66.0mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and methylene chloride (93.42mg, 1.10mmol), solvent toluene (1.0mL), small magneton, 90 DEG C of reaction 2h are added
Afterwards, methylene chloride (3 × 10mL) extracts, and organic phase depressurizes precipitation, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent,
300 mesh column layer chromatography silicone rubbers be filler, the target product (78.95mg, yield 78%) that column chromatography for separation purifies,1H NMR
(500MHz,CDCl3): δ=8.00-7.98 (d, 1H), 7.47-7.44 (td, 1H), 7.29-7.28 (d, 2H), 5.38 (s,
2H),2.64(s,3H)；13C NMR(125MHz,CDCl3): δ=165.63,140.09,131.81,130.91,129.95,
124.86,73.79,28.68,20.84ppm；
The preparation of embodiment 12:3- methyl benzoic acid chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, 3- tolyl aldehyde (66.0mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and small magneton, 90 DEG C of reaction 12h are added in methylene chloride (93.42mg, 1.10mmol), solvent toluene (1.0mL)
Afterwards, methylene chloride (3 × 10mL) extracts, and organic phase depressurizes precipitation, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent,
300 mesh column chromatography silica gels are filler, the target product (71.86mg, yield 71%) that column chromatography for separation purifies.
1H NMR(500MHz,CDCl3): δ=7.83-7.80 (m, 2H), 7.35-7.34 (d, 1H), 7.30-7.27 (t,
1H),5.31(s,2H),2.34(s,3H)；13C NMR(125MHz,CDCl3): δ=165.24,137.41,133.50,
129.46,127.81,127.44,126.08,74.06,20.23ppm.
The preparation of embodiment 13:4- methyl benzoic acid chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, 4- tolyl aldehyde (66.0mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and small magneton, 90 DEG C of reaction 12h are added in methylene chloride (93.42mg, 1.10mmol), solvent toluene (1.0mL)
Afterwards, methylene chloride (3 × 10mL) extracts, and organic phase depressurizes precipitation, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent,
300 mesh column chromatography silica gels are filler, the target product (79.96mg, yield 79%) that column chromatography for separation purifies.
1H NMR(500MHz,CDCl3): δ=7.83-7.80 (m, 2H), 7.35-7.34 (d, 1H), 7.30-7.27 (t,
1H),5.31(s,2H),2.34(s,3H)；13C NMR(125MHz,CDCl3): δ=165.24,137.41,133.50,
129.46,127.81,127.44,126.08,74.06,20.23ppm.
The preparation of embodiment 14:2- nitrobenzoic acid chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, 2- nitrobenzaldehyde (83.1mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and small magneton, 90 DEG C of reaction 12h are added in methylene chloride (93.42mg, 1.10mmol), solvent toluene (1.0mL)
Afterwards, methylene chloride (3 × 10mL) extracts, and organic phase depressurizes precipitation, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent,
300 mesh column layer chromatography silicone rubbers are filler, the target product (80.41mg, yield 68%) that column chromatography for separation purifies.
1H NMR (500MHz, CDCl3) δ 7.94 (dd, J=7.9,1.5Hz, 1H), 7.58 (dd, J=11.1,4.4Hz,
1H), 7.28 (d, J=8.1Hz, 1H), 7.22 (t, J=7.6Hz, 1H), 5.38 (s, 2H)13C NMR(125MHz,CDCl3)δ
164.5,140.8,134.0,132.2,124.5,119.9,75.2.
The preparation of embodiment 15:3- nitrobenzoic acid chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, 3- nitrobenzaldehyde (83.1mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and small magneton, 90 DEG C of reaction 12h are added in methylene chloride (93.42mg, 1.10mmol), solvent toluene (1.0mL)
Afterwards, methylene chloride (3 × 10mL) extracts, and organic phase depressurizes precipitation, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent,
300 mesh column chromatography silica gels are filler, the target product (82.78mg, yield 70%) that column chromatography for separation purifies.
1H NMR (500MHz, CDCl3) δ 8.92 (d, J=1.6Hz, 1H), 8.51-8.45 (m, 1H), 8.42 (d, J=
7.8Hz, 1H), 7.71 (t, J=8.0Hz, 1H), 5.46 (s, 2H)13C NMR(125MHz,CDCl3)δ163.14,147.36,
134.52,129.72,128.91,127.13,123.93,74.89.
The preparation of embodiment 16:4- nitrobenzoic acid chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, 4- nitrobenzaldehyde (83.1mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and methylene chloride (93.42mg, 1.10mmol), solvent toluene (1.0mL), small magneton, 90 DEG C of reactions are added
After 12h, methylene chloride (3 × 10mL) extraction, organic phase depressurizes precipitation, is elution with ethyl acetate: petroleum ether=1:30 solvent
Agent, 300 mesh column chromatography silica gels are filler, the target product (78.05mg, yield 66%) that column chromatography for separation purifies.
1H NMR(500MHz,CDCl3)δ8.35–8.30(m,2H),8.29-8.24(m,2H),5.44(s,2H).13C
NMR(125MHz,CDCl3)δ163.33,133.26,130.09,122.72,74.92.
The preparation of embodiment 17:2- methoxy benzoic acid chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, Benzaldehyde,2-methoxy (74.83mg, 0.55mmol), tetrabutyl iodate is added
Ammonium (20.3mg, 0.055mmol), sodium azide (71.50mg, 1.1mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and methylene chloride (93.42mg, 1.10mmol), small magneton is added in solvents tetrahydrofurane (1.0mL), and 90 DEG C anti-
After answering 12h, methylene chloride (3 × 10mL) extraction, organic phase depressurizes precipitation, is to wash with ethyl acetate: petroleum ether=1:30 solvent
De- agent, 300 mesh column layer chromatography silicone rubbers are filler, the target product (89.11mg, yield 81%) that column chromatography for separation purifies.1H NMR (500MHz, CDCl3) δ 7.88 (dd, J=7.9,1.8Hz, 1H), 7.56-7.50 (m, 1H), 7.03-6.97 (m,
2H),5.93(s,2H),3.92(s,3H).13C NMR(125MHz,CDCl3)δ163.4,160.1,134.8,132.2,120.1,
117.8,112.1,69.0,56.0
The preparation of embodiment 18:3- methoxy benzoic acid chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, m-methoxybenzaldehyde (74.83mg, 0.55mmol), tetrabutyl iodate is added
Ammonium (40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and small magneton, 90 DEG C of reaction 12h are added in methylene chloride (93.42mg, 1.10mmol), solvent benzol (1.0mL)
Afterwards, methylene chloride (3 × 10mL) extracts, and organic phase depressurizes precipitation, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent,
300 mesh column layer chromatography silicone rubbers are filler, the target product (88.00mg, yield 80%) that column chromatography for separation purifies.
1H NMR(500MHz,CDCl3) δ 7.68 (dd, J=7.7,1.0Hz, 1H), 7.59 (dd, J=2.5,1.5Hz,
1H), 7.38 (t, J=8.0Hz, 1H), 7.15 (ddd, J=8.3,2.6,0.8Hz, 1H), 5.39 (s, 2H), 3.86 (s, 3H)
13C NMR(125MHz,CDCl3)δ164.98,158.65,129.15,128.59,121.35,119.37,
113.21,74.20,54.47
The preparation of embodiment 19:4- methoxy benzoic acid chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, 4-methoxybenzaldehyde (74.83mg, 0.55mmol), tetrabutyl iodate is added
Ammonium (40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.40mL,
3.3mmol) and small magneton, 90 DEG C of reaction 10h are added in methylene chloride (93.42mg, 1.10mmol), solvent toluene (1.0mL)
Afterwards, methylene chloride (3 × 10mL) extracts, and organic phase depressurizes precipitation, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent,
300 mesh column layer chromatography silicone rubbers are filler, the target product (96.80mg, yield 88%) that column chromatography for separation purifies.
1H NMR(500MHz,CDCl3) δ 8.04 (d, J=8.9Hz, 2H), 6.95 (d, J=8.9Hz, 2H), 5.37 (s,
2H),3.88(s,3H).13C NMR(125MHz,CDCl3)δ164.73,162.99,131.08,120.20,112.83,73.87,
54.48.
The preparation of embodiment 20:4- ethyl benzoate chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, 4- ethylo benzene formaldehyde (73.74mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and small magneton, 90 DEG C of reaction 10h are added in methylene chloride (93.42mg, 1.10mmol), solvent toluene (1.0mL)
Afterwards, methylene chloride (3 × 10mL) extracts, and organic phase depressurizes precipitation, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent,
300 mesh column layer chromatography silicone rubbers be filler, the target product (87.14mg, yield 80%) that column chromatography for separation purifies,
1H NMR(500MHz,CDCl3) δ 8.00 (d, J=8.3Hz, 2H), 7.30 (d, J=8.3Hz, 2H), 5.38 (s,
2H), 2.76-2.68 (q, 2H), 1.25 (d, J=2.5Hz, 3H)13C NMR(125MHz,CDCl3)δ165.10,149.78,
129.10,127.09,125.34,73.96,28.01,14.15.
The preparation of embodiment 21:2- thiophenic acid chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, 2 thiophene carboxaldehyde (61.60mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and small magneton, 90 DEG C of reaction 6h are added in methylene chloride (93.42mg, 1.10mmol), solvent toluene (1.0mL)
Afterwards, methylene chloride (3 × 10mL) extracts, and organic phase depressurizes precipitation, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent,
300 mesh column layer chromatography silicone rubbers are filler, the target product (48.39mg, yield 50%) that column chromatography for separation purifies.
1H NMR(500MHz,CDCl3) δ 7.89 (dd, J=3.8,1.2Hz, 1H), 7.64 (dd, J=5.0,1.2Hz,
1H), 7.14 (dd, J=4.9,3.8Hz, 1H), 5.36 (s, 2H)13C NMR(125MHz,CDCl3)δ160.58,133.67,
132.69,127.03,74.16.
Embodiment 22: the preparation of di-2-ethylhexylphosphine oxide (thiophene-2-carboxylic acid ester)
Clean 15mL reaction under high pressure bottle is taken, 2 thiophene carboxaldehyde (61.60mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol), methylene chloride (93.43mg, 1.1mmol) and toluene (1.0mL), are added small magneton, after 90 DEG C of reaction 6h, two
Chloromethanes (3 × 10mL) extraction, organic phase depressurize precipitation, are eluant, eluent, 300 mesh with ethyl acetate: petroleum ether=1:30 solvent
Column chromatography silica gel is filler, the target product (76.64mg, yield 50%) that column chromatography for separation purifies,
1H NMR(500MHz,CDCl3) δ 7.89 (dd, J=3.8,1.2Hz, 1H), 7.62 (dd, J=5.0,1.2Hz,
1H), 7.12 (dd, J=4.9,3.8Hz, 1H), 6.16 (s, 1H)13C NMR(125MHz,CDCl3)δ159.70,133.77,
132.74,131.23,126.97,78.73.
The preparation of embodiment 23:2- naphthoic acid chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, 2- naphthaldehyde (90.78mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and small magneton, 90 DEG C of reaction 6h are added in methylene chloride (93.42mg, 1.10mmol), solvent toluene (1.0mL)
Afterwards, methylene chloride (3 × 10mL) extracts, and organic phase depressurizes precipitation, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent,
300 mesh column layer chromatography silicone rubbers are filler, the target product (95.60mg, yield 79%) that column chromatography for separation purifies.
1H NMR(500MHz,CDCl3) δ 8.67 (s, 1H), 8.09 (dd, J=8.6,1.7Hz, 1H), 7.98 (d, J=
8.0Hz, 1H), 7.91 (t, J=8.1Hz, 2H), 7.65-7.60 (m, 1H), 7.58 (dd, J=8.1,1.1Hz, 1H), 5.46
(s,2H).13C NMR(125MHz,CDCl3)δ165.24,134.84,131.39,130.80,128.46,127.70,127.40,
126.80,125.86,125.08,124.11,74.25.
The preparation of embodiment 24:2- furancarboxylic acid chloromethyl ester
Take clean 15mL reaction under high pressure bottle, be added furfural (52.81mg, 0.55mmol), tetrabutylammonium iodide (40.6mg,
0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL, 0.825mmol)
With methylene chloride (93.42mg, 1.10mmol), solvent toluene (1.0mL) is added small magneton, after 90 DEG C of reaction 3h, methylene chloride
(3 × 10mL) extraction, organic phase depressurize precipitation, are eluant, eluent, 300 mesh columns chromatography with ethyl acetate: petroleum ether=1:30 solvent
Silica gel is filler, the target product (71.27mg, yield 81%) that column chromatography for separation purifies,
1H NMR(500MHz,CDCl3) δ 7.66-7.63 (m, 1H), 7.30 (d, J=3.5Hz, 1H), 6.56 (dd, J=
3.5,1.7Hz,1H),5.37(s,2H).13C NMR(125MHz,CDCl3)δ156.88,146.25,142.46,118.58,
111.17,73.99.
The preparation of embodiment 25:5- methylfuran -2- monochlorome-thylchloroformate
Clean 15mL reaction under high pressure bottle is taken, 5- methylfuran -2- formaldehyde (60.52mg, 0.55mmol), tetrabutyl iodine is added
Change ammonium (40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide
(0.10mL, 0.825mmol) and methylene chloride (93.42mg, 1.10mmol), solvent toluene (1.0mL) are added small magneton, and 90
DEG C reaction 3h after, methylene chloride (3 × 10mL) extraction, organic phase depressurize precipitation, with ethyl acetate: petroleum ether=1:30 solvent is
Eluant, eluent, 300 mesh column layer chromatography silicone rubbers are filler, target product (74.65mg, the yield that column chromatography for separation purifies
78%).
1H NMR(500MHz,CDCl3) δ 7.21 (d, J=3.4Hz, 1H), 6.17 (dd, J=3.4,0.8Hz, 1H), 5.35
(s,2H),2.41(s,3H).13C NMR(125MHz,CDCl3)δ157.45,156.91,140.79,120.20,107.85,
73.77,59.39.
Embodiment 26: the preparation of tert-butyl (chloromethyl) phthalic acid
Clean 15mL reaction under high pressure bottle is taken, o-phthalaldehyde (73.2mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and small magneton, 90 DEG C of reaction 12h are added in methylene chloride (93.42mg, 1.10mmol), solvent toluene (1.0mL)
Afterwards, methylene chloride (3 × 10mL) extracts, and organic phase depressurizes precipitation, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent,
300 mesh column chromatography silica gels are filler, the target product (90.82mg, yield 61%) that column chromatography for separation purifies.
1H NMR(500MHz,CDCl3) δ 7.72 (dd, J=7.3,1.7Hz, 2H), 7.55 (td, J=6.6,1.6Hz,
2H),5.36(s,2H),1.59(s,9H).13C NMR(125MHz,CDCl3)δ166.30,165.24,132.82,130.50,
129.66,127.99,81.46,74.54,26.94.
The preparation of embodiment 27:4- methoxy benzoic acid benzyl ester
Clean 15mL reaction under high pressure bottle is taken, P-methoxybenzal-dehyde (74.8mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and benzyl chloride (1.0mL), it is added small magneton, after 100 DEG C of reaction 2h, methylene chloride (3 × 10mL) is extracted, organic phase
Precipitation is depressurized, with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column chromatography silica gels are filler, column chromatography for separation
Purify obtained target product (118.50mg, yield 89%).
1HNMR(500MHz,CDCl3): δ=8.04-8.02 (m, 2H), 7.44-7.43 (m, 2H), 7.39-7.36 (m,
2H),7.34-7.31(ddd,1H),5.33(s,2H),3.83(s,3H)；13CNMR(125MHz,CDCl3): δ=166.21,
163.47,136.34,131.77,128.59,128.16,128.12,122.57,113.65,66.41,55.43ppm；
The preparation of embodiment 28:4- methoxyl methyl benzoate
Clean 15mL reaction under high pressure bottle is taken, P-methoxybenzal-dehyde (74.8mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and iodomethane (1.0mL), it is added small magneton, after 90 DEG C of reaction 2h, methylene chloride (3 × 10mL) extraction is organic
It is molten to subtract each other pressure-off, with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column chromatography silica gels are filler, column chromatography point
The target product (76.71mg, yield 84%) obtained from purification.
1H NMR(500MHz,CDCl3): δ=8.00-7.98 (d, 2H), 6.92-6.91 (d, 2H), 3.88 (s, 3H),
3.86(s,3H)；13C NMR(125MHz,CDCl3): δ=166.88,163.33,131.51,122.61,113.60,55.41,
51.86ppm.
The preparation of embodiment 29:4- methoxy ethylbenzoate
Clean 15mL reaction under high pressure bottle is taken, P-methoxybenzal-dehyde (74.8mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and bromoethane (1.0mL), it is added small magneton, after 90 DEG C of reaction 2h, methylene chloride (3 × 10mL) extraction is organic
It is molten to subtract each other pressure-off, with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column chromatography silica gels are filler, column chromatography point
The target product (83.19mg, yield 84%) obtained from purification.
1H NMR(500MHz,CDCl3): δ=8.01-7.99 (d, 2H), 6.92-6.90 (d, 2H), 4.37-4.32 (q,
2H),3.85(s,3H),1.39-1.36(t,1H)；13C NMR(125MHz,CDCl3): δ=166.41,163.25,131.53,
125.92,122.96,114.01,113.54,60.63,55.40,14.38ppm.
The preparation of embodiment 30:4- methoxy benzoic acid butyl ester
Clean 15mL reaction under high pressure bottle is taken, P-methoxybenzal-dehyde (74.8mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and bromobutane (1.0mL), it is added small magneton, after 90 DEG C of reaction 2h, methylene chloride (3 × 10mL) extraction is organic
It is molten to subtract each other pressure-off, with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column chromatography silica gels are filler, column chromatography point
The target product (97.29mg, yield 85%) obtained from purification.
1H NMR(500MHz,CDCl3): δ=8.00-7.99 (d, 2H), 6.92-6.90 (d, 2H), 4.30-4.28 (t,
2H),3.85(s,3H),1.75-1.71(m,2H),1.49-1.45(m,2H),0.99-0.96 (t,3H)；13C NMR
(125MHz,CDCl3): δ=166.44,163.25,131.52,125.90,122.98,113.54,77.31,77.06,
76.81,64.52,55.39,30.84,19.29,13.77ppm.
The preparation of embodiment 31:4- methoxy benzoic acid allyl ester
Clean 15mL reaction under high pressure bottle is taken, P-methoxybenzal-dehyde (74.8mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and allyl chloride (1.0mL), it is added small magneton, after 90 DEG C of reaction 5h, methylene chloride (3 × 10mL) is extracted, and has
It is molten that machine subtracts each other pressure-off, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column chromatography silica gels are filler, column chromatography
The target product (84.52mg, yield 84%) that separating-purifying obtains.
1H NMR(500MHz,CDCl3): δ=7.96-7.94 (d, 2H), 6.86-6.84 (d, 2H), 6.00-5.93 (m,
1H),5.35-5.31(ddd,1H),5.22-5.19(dd,1H),4.74-4.72(dt,2H),3.79(s,3H)；13C NMR
(125MHz,CDCl3): δ=165.01,162.38,131.46,130.65,121.56,116.95,112.60,64.25,
54.41ppm；
The preparation of embodiment 32:4- methoxy benzoic acid allyl ester
Clean 15mL reaction under high pressure bottle is taken, P-methoxybenzal-dehyde (74.8mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and allyl bromide, bromoallylene (1.0mL), it is added small magneton, after 90 DEG C of reaction 5h, methylene chloride (3 × 10mL) is extracted, and has
It is molten that machine subtracts each other pressure-off, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column chromatography silica gels are filler, column chromatography
The target product (84.52mg, yield 84%) that separating-purifying obtains.
1H NMR (500MHz, CDCl3): δ=7.96-7.94 (d, 2H), 6.86-6.84 (d, 2H), 6.00-5.93 (m,
1H),5.35-5.31(ddd,1H),5.22-5.19(dd,1H),4.74-4.72(dt,2H),3.79(s,3H)；13C NMR
(125MHz, CDCl3): δ=165.01,162.38,131.46,130.65,121.56,116.95,112.60,64.25,
54.41ppm
The preparation of embodiment 33:4- methoxy benzoic acid allyl ester
Clean 15mL reaction under high pressure bottle is taken, P-methoxybenzal-dehyde (74.8mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and allyl iodide (1.0mL), it is added small magneton, after 90 DEG C of reaction 5h, methylene chloride (3 × 10mL) is extracted, and has
It is molten that machine subtracts each other pressure-off, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column chromatography silica gels are filler, column chromatography
The target product (80.49mg, yield 80%) that separating-purifying obtains.
1H NMR (500MHz, CDCl3): δ=7.96-7.94 (d, 2H), 6.86-6.84 (d, 2H), 6.00-5.93 (m,
1H),5.35-5.31(ddd,1H),5.22-5.19(dd,1H),4.74-4.72(dt,2H),3.79(s,3H)；13C NMR
(125MHz, CDCl3): δ=165.01,162.38,131.46,130.65,121.56,116.95,112.60,64.25,
54.41ppm
The preparation of embodiment 34:4- methoxy benzoic acid chloroethene ester
Clean 15mL reaction under high pressure bottle is taken, P-methoxybenzal-dehyde (74.8mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and 1,2- dichloroethanes (1.0mL), it is added small magneton, after 90 DEG C of reaction 6h, methylene chloride (3 × 10mL) extracts
It taking, organic phase depressurizes precipitation, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column chromatography silica gels are filler,
The target product (100.06mg, yield 85%) that column chromatography for separation purifies.
1H NMR(500MHz,CDCl3): δ=8.03-8.01 (d, 2H), 6.94-6.92 (d, 2H), 4.55-4.53 (t,
2H),3.87(s,3H),3.82-3.79(t,3H)；13C NMR(125MHz,CDCl3): δ=165.92,163.63,131.82,
125.93,122.01,113.71,64.19,55.46,41.81ppm.
The preparation of embodiment 35:2- methyl benzoic acid chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, 2- tolyl aldehyde (66.0mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and methylene chloride (1.0mL), it is added small magneton, after 90 DEG C of reaction 2h, methylene chloride (3 × 10mL) is extracted, and has
It is molten that machine subtracts each other pressure-off, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column layer chromatography silicone rubbers are filler, column layer
The target product (78.95mg, yield 78%) that analysis separating-purifying obtains,
1H NMR(500MHz,CDCl3): δ=8.00-7.98 (d, 1H), 7.47-7.44 (td, 1H), 7.29-7.28 (d,
2H),5.38(s,2H),2.64(s,3H)；13C NMR(125MHz,CDCl3): δ=165.63,140.09,131.81,
130.91,129.95,124.86,73.79,28.68,20.84ppm；
The preparation of embodiment 36:3- methyl benzoic acid chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, 3- tolyl aldehyde (66.0mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and methylene chloride (1.0mL), it is added small magneton, after 90 DEG C of reaction 12h, methylene chloride (3 × 10mL) is extracted, and has
It is molten that machine subtracts each other pressure-off, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column chromatography silica gels are filler, column chromatography
The target product (71.86mg, yield 71%) that separating-purifying obtains.
1H NMR(500MHz,CDCl3): δ=7.83-7.80 (m, 2H), 7.35-7.34 (d, 1H), 7.30-7.27 (t,
1H),5.31(s,2H),2.34(s,3H)；13C NMR(125MHz,CDCl3): δ=165.24,137.41,133.50,
129.46,127.81,127.44,126.08,74.06,20.23ppm.
The preparation of embodiment 37:4- methyl benzoic acid chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, 4- tolyl aldehyde (66.0mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and methylene chloride (1.0mL), it is added small magneton, after 90 DEG C of reaction 12h, methylene chloride (3 × 10mL) is extracted, and has
It is molten that machine subtracts each other pressure-off, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column chromatography silica gels are filler, column chromatography
The target product (79.96mg, yield 79%) that separating-purifying obtains.
1H NMR(500MHz,CDCl3): δ=7.83-7.80 (m, 2H), 7.35-7.34 (d, 1H), 7.30-7.27 (t,
1H),5.31(s,2H),2.34(s,3H)；13C NMR(125MHz,CDCl3): δ=165.24,137.41,133.50,
129.46,127.81,127.44,126.08,74.06,20.23ppm；
The preparation of embodiment 38:2- nitrobenzoic acid chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, 2- nitrobenzaldehyde (83.1mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and methylene chloride (1.0mL), it is added small magneton, after 90 DEG C of reaction 12h, methylene chloride (3 × 10mL) is extracted, and has
It is molten that machine subtracts each other pressure-off, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column layer chromatography silicone rubbers are filler, column layer
The target product (80.41mg, yield 68%) that analysis separating-purifying obtains.
1H NMR (500MHz, CDCl3) δ 7.94 (dd, J=7.9,1.5Hz, 1H), 7.58 (dd, J=11.1,4.4Hz,
1H), 7.28 (d, J=8.1Hz, 1H), 7.22 (t, J=7.6Hz, 1H), 5.38 (s, 2H)13C NMR(125MHz,CDCl3)δ
164.5,140.8,134.0,132.2,124.5,119.9,75.2.
The preparation of embodiment 39:3- nitrobenzoic acid chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, 3- nitrobenzaldehyde (83.1mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and methylene chloride (1.0mL), it is added small magneton, after 90 DEG C of reaction 12h, methylene chloride (3 × 10mL) is extracted, and has
It is molten that machine subtracts each other pressure-off, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column chromatography silica gels are filler, column chromatography
The target product (82.78mg, yield 70%) that separating-purifying obtains.
1H NMR (500MHz, CDCl3) δ 8.92 (d, J=1.6Hz, 1H), 8.51-8.45 (m, 1H), 8.42 (d, J=
7.8Hz, 1H), 7.71 (t, J=8.0Hz, 1H), 5.46 (s, 2H)13C NMR(125MHz,CDCl3)δ163.14,147.36,
134.52,129.72,128.91,127.13,123.93,74.89.
The preparation of embodiment 40:4- nitrobenzoic acid chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, 4- nitrobenzaldehyde (83.1mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and methylene chloride (1.0mL), it is added small magneton, after 90 DEG C of reaction 12h, methylene chloride (3 × 10mL) extraction,
Organic phase depressurizes precipitation, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column chromatography silica gels are filler, column layer
The target product (78.05mg, yield 66%) that analysis separating-purifying obtains.
1H NMR(500MHz,CDCl3)δ8.35–8.30(m,2H),8.29-8.24(m,2H),5.44(s,2H).13C
NMR(125MHz,CDCl3)δ163.33,133.26,130.09,122.72,74.92.
The preparation of embodiment 41:2- methoxy benzoic acid chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, Benzaldehyde,2-methoxy (74.83mg, 0.55mmol), tetrabutyl iodate is added
Ammonium (20.3mg, 0.055mmol), sodium azide (71.50mg, 1.1mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and methylene chloride (1.0mL), it is added small magneton, after 90 DEG C of reaction 12h, methylene chloride (3 × 10mL) is extracted, and has
It is molten that machine subtracts each other pressure-off, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column layer chromatography silicone rubbers are filler, column layer
The target product (89.11mg, yield 81%) that analysis separating-purifying obtains.
1H NMR (500MHz, CDCl3) δ 7.88 (dd, J=7.9,1.8Hz, 1H), 7.56-7.50 (m, 1H), 7.03-
6.97(m,2H),5.93(s,2H),3.92(s,3H).13C NMR(125MHz,CDCl3)δ163.4,160.1,134.8,
132.2,120.1,117.8,112.1,69.0,56.0
The preparation of embodiment 42:3- methoxy benzoic acid chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, m-methoxybenzaldehyde (74.83mg, 0.55mmol), tetrabutyl iodate is added
Ammonium (40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and methylene chloride (1.0mL), it is added small magneton, after 90 DEG C of reaction 12h, methylene chloride (3 × 10mL) is extracted, and has
It is molten that machine subtracts each other pressure-off, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column layer chromatography silicone rubbers are filler, column layer
The target product (88.00mg, yield 80%) that analysis separating-purifying obtains.
1H NMR(500MHz,CDCl3) δ 7.68 (dd, J=7.7,1.0Hz, 1H), 7.59 (dd, J=2.5,1.5Hz,
1H), 7.38 (t, J=8.0Hz, 1H), 7.15 (ddd, J=8.3,2.6,0.8Hz, 1H), 5.39 (s, 2H), 3.86 (s, 3H)
13C NMR(125MHz,CDCl3)δ164.98,158.65,129.15,128.59,121.35,119.37,
113.21,74.20,54.47
The preparation of embodiment 43:4- methoxy benzoic acid chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, 4-methoxybenzaldehyde (74.83mg, 0.55mmol), tetrabutyl iodate is added
Ammonium (40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.40mL,
3.3mmol) and methylene chloride (1.0mL), it is added small magneton, after 90 DEG C of reaction 10h, methylene chloride (3 × 10mL) is extracted, organic
It is molten to subtract each other pressure-off, with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column layer chromatography silicone rubbers are filler, column chromatography
The target product (96.80mg, yield 88%) that separating-purifying obtains.
1H NMR(500MHz,CDCl3) δ 8.04 (d, J=8.9Hz, 2H), 6.95 (d, J=8.9Hz, 2H), 5.37 (s,
2H),3.88(s,3H).13C NMR(125MHz,CDCl3)δ164.73,162.99,131.08,120.20,112.83,73.87,
54.48.
The preparation of embodiment 44:4- ethyl benzoate chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, 4- ethylo benzene formaldehyde (73.74mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and methylene chloride (1.0mL), it is added small magneton, after 90 DEG C of reaction 10h, methylene chloride (3 × 10mL) is extracted, and has
It is molten that machine subtracts each other pressure-off, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column layer chromatography silicone rubbers are filler, column layer
The target product (87.14mg, yield 80%) that analysis separating-purifying obtains,
1H NMR(500MHz,CDCl3) δ 8.00 (d, J=8.3Hz, 2H), 7.30 (d, J=8.3Hz, 2H), 5.38 (s,
2H), 2.76-2.68 (q, 2H), 1.25 (d, J=2.5Hz, 3H)13C NMR(125MHz,CDCl3)δ165.10,149.78,
129.10,127.09,125.34,73.96,28.01,14.15.
The preparation of embodiment 45:2- thiophenic acid chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, 2 thiophene carboxaldehyde (61.60mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and methylene chloride (1.0mL), it is added small magneton, after 90 DEG C of reaction 6h, methylene chloride (3 × 10mL) is extracted, and has
It is molten that machine subtracts each other pressure-off, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column layer chromatography silicone rubbers are filler, column layer
The target product (48.39mg, yield 50%) that analysis separating-purifying obtains.
1H NMR(500MHz,CDCl3) δ 7.89 (dd, J=3.8,1.2Hz, 1H), 7.64 (dd, J=5.0,1.2Hz,
1H), 7.14 (dd, J=4.9,3.8Hz, 1H), 5.36 (s, 2H)13C NMR(125MHz,CDCl3)δ160.58,133.67,
132.69,127.03,74.16.
Embodiment 46: the preparation of di-2-ethylhexylphosphine oxide (thiophene-2-carboxylic acid ester)
Clean 15mL reaction under high pressure bottle is taken, 2 thiophene carboxaldehyde (61.60mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol), methylene chloride (1.0mL), is added small magneton, and after 90 DEG C of reaction 6h, methylene chloride (3 × 10mL) extraction is organic
It is molten to subtract each other pressure-off, with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column chromatography silica gels are filler, column chromatography point
From the obtained target product (76.64mg, yield 50%) of purification,
1H NMR(500MHz,CDCl3) δ 7.89 (dd, J=3.8,1.2Hz, 1H), 7.62 (dd, J=5.0,1.2Hz,
1H), 7.12 (dd, J=4.9,3.8Hz, 1H), 6.16 (s, 1H)13C NMR(125MHz,CDCl3)δ159.70,133.77,
132.74,131.23,126.97,78.73.
The preparation of embodiment 47:2- naphthoic acid chloromethyl ester
Clean 15mL reaction under high pressure bottle is taken, 2- naphthaldehyde (90.78mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and methylene chloride (1mL), it is added small magneton, after 90 DEG C of reaction 6h, methylene chloride (3 × 10mL) is extracted, organic
It is molten to subtract each other pressure-off, with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column layer chromatography silicone rubbers are filler, column chromatography
The target product (95.60mg, yield 79%) that separating-purifying obtains.
1H NMR(500MHz,CDCl3) δ 8.67 (s, 1H), 8.09 (dd, J=8.6,1.7Hz, 1H), 7.98 (d, J=
8.0Hz, 1H), 7.91 (t, J=8.1Hz, 2H), 7.65-7.60 (m, 1H), 7.58 (dd, J=8.1,1.1Hz, 1H), 5.46
(s,2H).13C NMR(125MHz,CDCl3)δ165.24,134.84,131.39,130.80,128.46,127.70,127.40,
126.80,125.86,125.08,124.11,74.25.
The preparation of embodiment 48:2- furancarboxylic acid chloromethyl ester
Take clean 15mL reaction under high pressure bottle, be added furfural (52.81mg, 0.55mmol), tetrabutylammonium iodide (40.6mg,
0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL, 0.825mmol)
With methylene chloride (1mL), it being added small magneton, after 90 DEG C of reaction 3h, methylene chloride (3 × 10mL) extraction, organic phase depressurizes precipitation,
With ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column chromatography silica gels are filler, and column chromatography for separation purifies to obtain
Target product (71.27mg, yield 81%),
1H NMR(500MHz,CDCl3) δ 7.66-7.63 (m, 1H), 7.30 (d, J=3.5Hz, 1H), 6.56 (dd, J=
3.5,1.7Hz,1H),5.37(s,2H).13C NMR(125MHz,CDCl3)δ156.88,146.25,142.46,118.58,
111.17,73.99.
The preparation of embodiment 49:5- methylfuran -2- monochlorome-thylchloroformate
Clean 15mL reaction under high pressure bottle is taken, 5- methylfuran -2- formaldehyde (60.52mg, 0.55mmol), tetrabutyl iodine is added
Change ammonium (40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide
(0.10mL, 0.825mmol) and methylene chloride (1mL), is added small magneton, after 90 DEG C of reaction 3h, methylene chloride (3 × 10mL) extraction
It takes, organic phase depressurizes precipitation, and with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column layer chromatography silicone rubbers are to fill out
Material, the target product (74.65mg, yield 78%) that column chromatography for separation purifies.
1H NMR(500MHz,CDCl3) δ 7.21 (d, J=3.4Hz, 1H), 6.17 (dd, J=3.4,0.8Hz, 1H), 5.35
(s,2H),2.41(s,3H).13C NMR(125MHz,CDCl3)δ157.45,156.91,140.79,120.20,107.85,
73.77,59.39.
Embodiment 50: the preparation of tert-butyl (chloromethyl) phthalic acid
Clean 15mL reaction under high pressure bottle is taken, o-phthalaldehyde (73.2mg, 0.55mmol), tetrabutylammonium iodide is added
(40.6mg, 0.11mmol), sodium azide (107.25mg, 1.65mmol), oxidant tert-butyl hydroperoxide (0.10mL,
0.825mmol) and methylene chloride (1mL), it is added small magneton, after 90 DEG C of reaction 12h, methylene chloride (3 × 10mL) is extracted, organic
It is molten to subtract each other pressure-off, with ethyl acetate: petroleum ether=1:30 solvent is eluant, eluent, and 300 mesh column chromatography silica gels are filler, column chromatography point
The target product (90.82mg, yield 61%) obtained from purification.
1H NMR(500MHz,CDCl3) δ 7.72 (dd, J=7.3,1.7Hz, 2H), 7.55 (td, J=6.6,1.6Hz,
2H),5.36(s,2H),1.59(s,9H).13C NMR(125MHz,CDCl3)δ166.30,165.24,132.82,130.50,
129.66,127.99,81.46,74.54,26.94。
Claims (10)
1. a kind of preparation method of the carboxylic acid ester compound as shown in formula (1), formula (2) or formula (3), it is characterised in that the side
Method carries out as follows:
By aldehyde compound, tetrabutylammonium iodide, sodium azide, oxidant tert-butyl hydroperoxide and halogenated alkane, being dissolved in has
In solvent, 1~12h is reacted at 90-100 DEG C, after reaction, reaction solution is post-treated to obtain formula (1), formula (2) or formula
(3) compound represented；The aldehyde compound, tetrabutylammonium iodide, sodium azide, tert-butyl hydroperoxide and halogenated alkane
The ratio between the amount of substance be 1:0.1~0.2:2~3:1.5~6:2~5；The C atom number of the halogenated alkane is 1~5；
Wherein: in formula (1), formula (2) or formula (3), the R1For C1~4Alkyl, methoxyl group, nitro, phenyl, naphthalene, halogen or three
Methyl fluoride；The R2For C1~4The phenyl that alkyl, benzyl, phenyl or alkyl, halogen atom replace；The R3For H, methyl, ethyl or
Other chain-like alkyls；The R4For C1~4The phenyl that alkyl, benzyl, phenyl or alkyl, halogen atom replace；The aldehydes chemical combination
Object is the aldehyde with aromatics property.
2. the synthetic method of carboxylic acid ester compound as described in claim 1, it is characterised in that the aldehyde compound are as follows:
P-methoxybenzal-dehyde, m-methoxybenzaldehyde, o-methoxybenzaldehyde, p-tolyl aldehyde, tolyl aldehyde, adjacent methyl
Benzaldehyde, paranitrobenzaldehyde, m-nitrobenzaldehyde, o-nitrobenzaldehyde, 2- naphthaldehyde, furfural, 5- methylfuran aldehyde, 2- thiophene
Pheno formaldehyde or o-phthalaldehyde.
3. the synthetic method of carboxylic acid ester compound as described in claim 1, it is characterised in that institute
The halogenated alkane stated are as follows: methylene chloride, carbon tetrachloride, benzyl chloride, cylite, iodomethane, bromoethane, bis- chloroethene of 1,2-
Alkane, bromobutane, allyl chloride, allyl bromide, bromoallylene or allyl iodide.
4. the synthetic method of carboxylic acid ester compound as described in claim 1, it is characterised in that the organic solvent is first
Benzene, tetrahydrofuran, N,N-dimethylformamide or benzene.
5. the synthetic method of carboxylic acid ester compound as described in claim 1, it is characterised in that the volume of the organic solvent
Dosage is calculated as 0.2~2mL/mmol with the amount of the substance of aldehyde.
6. the synthetic method of carboxylic acid ester compound as described in claim 1, it is characterised in that the reaction solution post-processing
Method are as follows: after reaction, reaction solution is extracted with dichloromethane, the dry vacuum removal of extract liquor, after solvent under reduced pressure concentration, gained
Concentrate carries out column chromatography for separation with 200~300 mesh silica gel, and eluant, eluent is the mixing of ethyl acetate and petroleum ether volume ratio 1:20
Liquid, collects the eluent containing target compound, and concentrate drying obtains formula (1), formula (2) or formula (3) compound represented.
7. a kind of preparation method of the carboxylic acid ester compound as shown in formula (1), formula (2) or formula (3), it is characterised in that the side
Method carries out as follows:
Tetrabutylammonium iodide, sodium azide and oxidant tert-butyl hydroperoxide are added into aldehyde compound, is dissolved in alkyl halide
In hydrocarbon, 1~12h is reacted at 90~100 DEG C, after reaction, reaction solution is post-treated to obtain formula (1), formula (2) or formula (3)
Compound represented；The aldehyde compound, tetrabutylammonium iodide, sodium azide and tert-butyl hydroperoxide substance amount it
Than for 1:0.1~0.2:2~3:1.5~6；The C atom number of the halogenated alkane is 1~5；
Wherein: in formula (1), formula (2) or formula (3), the R1For C1~4Alkyl, methoxyl group, nitro, phenyl, naphthalene, halogen or three
Methyl fluoride；The R2For C1~4The phenyl that alkyl, benzyl, phenyl or alkyl, halogen atom replace；The R3For H, methyl, ethyl or
Other chain-like alkyls；The R4For C1~4The phenyl that alkyl, benzyl, phenyl or alkyl, halogen atom replace；The aldehydes chemical combination
Object is the aldehyde with aromatics property.
8. the synthetic method of carboxylic acid ester compound as claimed in claim 7, it is characterised in that the aldehyde compound are as follows:
P-methoxybenzal-dehyde, m-methoxybenzaldehyde, o-methoxybenzaldehyde, p-tolyl aldehyde, tolyl aldehyde, adjacent methyl
Benzaldehyde, paranitrobenzaldehyde, m-nitrobenzaldehyde, o-nitrobenzaldehyde, 2- naphthaldehyde, furfural, 5- methylfuran aldehyde, 2- thiophene
Pheno formaldehyde or o-phthalaldehyde.
9. the synthetic method of carboxylic acid ester compound as claimed in claim 7, it is characterised in that the halogenated alkane are as follows: two
Chloromethanes, chloroform, carbon tetrachloride, benzyl chloride, cylite, iodomethane, bromoethane, 1,2- dichloroethanes, bromobutane, allyl
Base chlorine, allyl bromide, bromoallylene or allyl iodide.
10. the synthetic method of carboxylic acid ester compound as claimed in claim 7, it is characterised in that the reaction solution post-processing
Method are as follows: after reaction, reaction solution is extracted with dichloromethane, the dry vacuum removal of extract liquor, after solvent under reduced pressure concentration, gained
Concentrate carries out column chromatography for separation with 200~300 mesh silica gel, and eluant, eluent is the mixing of ethyl acetate and petroleum ether volume ratio 1:20
Liquid, collects the eluent containing target compound, and concentrate drying obtains formula (1), formula (2) or formula (3) compound represented.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4874887A (en) * | 1987-02-13 | 1989-10-17 | Lucky, Ltd. | Process for the preparation of pyrethroid type ester compounds |
| CN1753888A (en) * | 2003-03-01 | 2006-03-29 | 阿斯利康(瑞典)有限公司 | Hydroxymethyl substituted dihydroisoxazole derivatives useful as antibiotic agents |
| CN102531956A (en) * | 2010-12-21 | 2012-07-04 | 浙江九洲药业股份有限公司 | Intermediate for preparing agomelatine and relevant preparation method |
| CN102816134A (en) * | 2012-08-03 | 2012-12-12 | 南开大学 | 1,2,3-thiadiazole-containing sulfilimine (sulfonimine) compounds and their preparation method and use |
| CN102942601A (en) * | 2012-11-30 | 2013-02-27 | 蔡进 | Method for preparing fondaparinux sodium intermediate |
| CN103596951A (en) * | 2011-04-08 | 2014-02-19 | 阿弗拉克西斯控股股份有限公司 | 8-ethyl-6-(aryl)pyrido [2,3-d]pyrimidin-7(8h)-ones for the treatment of nervous system disorders and cancer |
| CN104926646A (en) * | 2014-03-20 | 2015-09-23 | 谢阳 | Method for chemical synthesis of tanshinol and related analogues |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6506908B2 (en) * | 2000-04-21 | 2003-01-14 | Merck & Co., Inc. | Process for preparing 3-hydroxymethyl-4-(aryl or heterocyclic)-cyclopentanones |
-
2016
- 2016-11-16 CN CN201611006903.6A patent/CN106588644B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4874887A (en) * | 1987-02-13 | 1989-10-17 | Lucky, Ltd. | Process for the preparation of pyrethroid type ester compounds |
| CN1753888A (en) * | 2003-03-01 | 2006-03-29 | 阿斯利康(瑞典)有限公司 | Hydroxymethyl substituted dihydroisoxazole derivatives useful as antibiotic agents |
| CN102531956A (en) * | 2010-12-21 | 2012-07-04 | 浙江九洲药业股份有限公司 | Intermediate for preparing agomelatine and relevant preparation method |
| CN103596951A (en) * | 2011-04-08 | 2014-02-19 | 阿弗拉克西斯控股股份有限公司 | 8-ethyl-6-(aryl)pyrido [2,3-d]pyrimidin-7(8h)-ones for the treatment of nervous system disorders and cancer |
| CN102816134A (en) * | 2012-08-03 | 2012-12-12 | 南开大学 | 1,2,3-thiadiazole-containing sulfilimine (sulfonimine) compounds and their preparation method and use |
| CN102942601A (en) * | 2012-11-30 | 2013-02-27 | 蔡进 | Method for preparing fondaparinux sodium intermediate |
| CN104926646A (en) * | 2014-03-20 | 2015-09-23 | 谢阳 | Method for chemical synthesis of tanshinol and related analogues |
Non-Patent Citations (1)
| Title |
|---|
| Bu4NI-catalyzed and tBuOOH-oxidized Esterification of Aldehydes with Alkyl Halides in Water;Wang, Qian-Qian et al;《 Asian Journal of Organic Chemistry》;20160908;第1304-1308页 |
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