CN114031497A - Ring-opening double-chlorination reaction method of cyclopropenone and oxygen heterocyclic compound - Google Patents

Ring-opening double-chlorination reaction method of cyclopropenone and oxygen heterocyclic compound Download PDF

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CN114031497A
CN114031497A CN202111343511.XA CN202111343511A CN114031497A CN 114031497 A CN114031497 A CN 114031497A CN 202111343511 A CN202111343511 A CN 202111343511A CN 114031497 A CN114031497 A CN 114031497A
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cyclopropenone
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周云兵
刘毅
缪威航
刘妙昌
吴华悦
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Wenzhou University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/46—Preparation of carboxylic acid esters from ketenes or polyketenes
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    • B01J27/06—Halogens; Compounds thereof
    • B01J27/08—Halides
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    • B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
    • B01J27/06—Halogens; Compounds thereof
    • B01J27/08—Halides
    • B01J27/122—Halides of copper
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
    • B01J27/06—Halogens; Compounds thereof
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    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
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    • B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
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    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
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Abstract

The invention discloses a ring-opening double-chlorination reaction method of cyclopropenone and an oxygen heterocyclic compound, which is carried out in CuCl2And AlCl3Under the catalysis, the cyclopropenone and the oxygen heterocyclic compound carry out ring-opening double chlorination reaction to prepare the 3-A chloroacrylate compound. The method can construct the cleavage of two C-Cl bonds and one C-O bond as well as two C-O bonds and one C-C bond in one step, and has high atom economy, excellent substrate application range and gram-level reaction capability.

Description

Ring-opening double-chlorination reaction method of cyclopropenone and oxygen heterocyclic compound
Technical Field
The application belongs to the technical field of organic synthesis methodology, and particularly relates to a ring-opening double-chlorination reaction method of cyclopropenone and an oxygen heterocyclic compound.
Background
Beta-unsaturated esters are an important chemical structure and are widely found in pesticides, natural products, additives, polymer modifiers and plasticizers. Among them, 3-chloroacrylates are valuable building blocks in organic synthetic chemistry, and their derivatives show a series of physiological activities and pharmacological activities. In view of their importance, various efficient methods for preparing 3-chloroacrylates have been reported in succession. One of the most common synthetic strategies is hydrohalogenation of propargyl esters, which results in a mixture of products of the Z and E configurations, with the E isomer predominating in some cases (see j.org.chem.1965,30,3141; j.chem.soc., chem.commun.1990, 1643.; j.org.chem.1992,57,709; chem.eur.j.2017,23,12739.; ACS catal.2017,7,6798.; org.lett.2019,21,4531; angelw.chem.int.ed.2020, 59,2904.). Tanaka's topic group reported that rhodium (I) catalyzed selective chlorination esterification of terminal alkynes with chloroformates, by introducing a chlorine atom and an ester group to the alkyne, 3-haloacrylates can be synthesized directly (see j.am.chem.soc.1998,120, 12365.). In addition, in excess of CuCl2In the presence of palladium catalysed multicomponent reactions of terminal alkynes, aliphatic alcohols and carbon monoxide have proved to be a powerful alternative to traditional synthetic strategies (j.am.chem.soc.1972,94,2712; j.org.chem.1978,43,131.; j.org.chem.1999,64,5984.; j.org.chem.2000,65,6561; org.lett.2003,5,4429; j.org.chem.2005,70,477.). However, these methods still require precious metals, toxic CO or large excesses of highly corrosive acids, which limit their use in complex 3-chloroacrylate syntheses. Thus, the inventors have developed a novel CuCl material with reference to the previous work2And AlCl3Catalyzing the ring-opening double-chlorination reaction of the cyclopropenone and the oxygen heterocyclic compound.
Disclosure of Invention
The invention aims to overcome the defects of harsh synthesis reaction conditions and high cost of 3-chloroacrylate compounds in the prior art, and enriches 3-chloroacrylate compoundsThe synthesis strategy of the acrylate compound provides a method for synthesizing CuCl2And AlCl3The method can construct the cracking of two C-Cl bonds and one C-O bond as well as two C-O bonds and one C-C bond in one step, and has high atom economy, excellent substrate application range and gram-level reaction capability.
The ring-opening double-chlorination reaction method of cyclopropenone and an oxygen heterocyclic compound provided by the invention comprises the following steps:
cyclopropenone compound shown as formula 1, oxacyclo compound shown as formula 2 and CuCl2Adding the auxiliary agent and the organic solvent into a reactor with a stirrer in sequence, then stirring the reaction mixture to react under the condition of inert atmosphere at 60-150 ℃, and carrying out post-treatment after the reaction is completed to obtain a 3-chloroacrylate compound shown in a formula b; the reaction formula is as follows:
Figure BDA0003353039720000021
in the above reaction formula, R1,R2Independently of one another, from hydrogen, C1-20Alkyl radical, C1-20Haloalkyl, C6-20Aryl, substituted C6-20An aryl group; provided that R is1,R2Not simultaneously selected from hydrogen; wherein said substituted C6-20The substituent of the aryl is selected from halogen and C1-6Alkyl radical, C1-6Alkoxy, -CN, C1-6Alkylcarbonyl group, C1-6An alkoxycarbonyl group;
n is 0,1,2,3 or 4;
R3,R4independently of one another, from hydrogen, C1-20Alkyl radical, C1-20A haloalkyl group; and/or when n is 0, R3,R4Are linked to each other to form a five-to seven-membered carbocyclic fused epoxy structure
Figure BDA0003353039720000031
Preferably, R1,R2Independently of one another, from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, trifluoromethyl, trichloromethyl, phenyl, naphthyl, anthracenyl, substituted phenyl, substituted naphthyl, substituted anthracenyl; provided that R is1,R2Not simultaneously selected from hydrogen; wherein the substituents in said substituted are selected from the group consisting of fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, methoxy, ethoxy, tert-butoxy, -CN, acetyl, methoxycarbonyl, ethoxycarbonyl;
n is 0,1,2,3 or 4;
R3,R4independently of one another, from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, trifluoromethyl, trichloromethyl; and/or when n is 0, R3,R4Are linked to each other to form a saturated five-to seven-membered carbocyclic fused epoxy structure
Figure BDA0003353039720000032
Most preferably, R1,R2Independently of one another, from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, phenyl or substituted phenyl; provided that R is1,R2Not simultaneously selected from hydrogen; wherein the substituents in said substituted are selected from the group consisting of fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, methoxy, ethoxy, tert-butoxy, -CN, acetyl, methoxycarbonyl, ethoxycarbonyl;
n is 0,1,2,3 or 4;
R3,R4independently of one another, from hydrogen, methyl; and/or when n is 0, R3,R4Are connected with each other to form
Figure BDA0003353039720000033
A structure wherein m is 1,2 or 3.
According to the aforementioned reaction method of the present invention, whereinThe auxiliary agent is AlCl3、NbCl5、CoCl2、ZnCl2Any one or more of them; preferably, the auxiliary agent is AlCl3。
According to the reaction method of the present invention, wherein the organic solvent is acetonitrile; and/or the compound of formula 2 simultaneously acts as a reaction solvent. Preferably, the organic solvent is acetonitrile.
According to the reaction method of the present invention, the reaction temperature is 80-120 ℃, preferably 100-120 ℃, and most preferably 120 ℃.
According to the reaction method, the reaction time of the stirring reaction is 4-48 h, preferably 8-24 h, and more preferably 10-12 h.
According to the reaction method, the cyclopropenone compound shown in formula 1, the oxacyclo compound shown in formula 2 and CuCl2The feeding molar ratio of the auxiliary agent is 1 (1-3) to (1-5) to (0.1-0.5); preferably, the cyclopropenone compound shown in formula 1, the oxacyclo compound shown in formula 2 and CuCl2The feeding molar ratio of the auxiliary agent is 1:1.5:2: 0.3.
According to the reaction method of the present invention, the inert atmosphere is a nitrogen atmosphere and/or an argon atmosphere, and preferably a nitrogen atmosphere.
The reaction method according to the present invention, wherein the post-treatment operation is as follows: after the reaction is completed, adding water into the reaction mixture for quenching, adding ethyl acetate for extraction, drying the organic phase, filtering and concentrating under reduced pressure to obtain a residue, and separating the residue by silica gel column chromatography to obtain the 3-chloroacrylate compound shown in formula 3.
The method of the invention achieves the following beneficial technical effects:
the synthetic strategy of the invention overcomes the defects that the 3-chloroacrylate compounds prepared by the prior art need to use noble metal, toxic CO or excessive high-corrosivity acid, and has the advantages of economy, low price, easy operation and high yield of target products. The method can construct the cleavage of two C-Cl bonds and one C-O bond as well as two C-O bonds and one C-C bond in one step, and has high atom economy, excellent substrate application range and gram-level reaction capability.
Detailed Description
The present invention will be described in more detail with reference to specific examples. In the following, unless otherwise specified, all methods involved are conventional in the art. The reagents used are all obtained commercially and without further purification treatment, as is conventional in the art, and/or prepared according to synthetic methods known in the art.
Examples 1-20 optimization of reaction conditions
The cyclopropenone and tetrahydrofuran shown in the formula 1a are used as raw materials, the influence of different reaction conditions on the yield of the target product 3b is researched, representative examples 1-20 are selected, and the results are shown in table 1. The reaction formula is as follows:
Figure BDA0003353039720000051
table 1:
Figure BDA0003353039720000052
Figure BDA0003353039720000061
bindicating that the reaction was carried out under a nitrogen atmosphere.
Taking example 20 as an example, a typical reaction run is as follows:
cyclopropenone 1a (0.2mmol, 1.0 equiv.), CuCl2(0.4mmol, 2.0 equiv.), AlCl3(0.06mmol), tetrahydrofuran (0.3mmol, 1.5 equiv.), and CH3CN (2mL) was charged to a 10mL reaction tube. The reaction mixture was then stirred at 120 ℃ for 10 hours under a nitrogen atmosphere. After completion of the reaction, 2.0mL of water was added to the reaction mixture, the reaction solution was extracted with ethyl acetate (3 × 2mL), the combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure,the remaining residue was purified by silica gel column chromatography using n-hexane/ethyl acetate (v/v 20:1) as the eluting solvent to give the desired product 3b in 86% yield. And (3) product characterization:1H NMR(400MHz,Chloroform-d)δ7.33–7.22(m,8H),7.18–7.15(m,2H),4.37(t,J＝4.8Hz,2H),3.64–3.56(m,2H),1.98–1.88(m,4H).13C NMR(125MHz,Chloroform-d)δ136.6,134.5,133.6,133.4,129.6,129.0,128.4,128.1,128.0,64.7,44.3,29.0,25.9.HRMS:(ESI)calculated for C19H19Cl2O2[M+H]+349.0757,found 335.0751.。
in examples 1 to 19, reaction variables are shown in table 1, except that tetrahydrofuran was used as a solvent and the reaction was carried out under an air atmosphere, which is different from example 20.
Examples 21-37 substrate extension of the Ring opening Dichlorination reaction of Cyclopropenone with an Oxacyclo Compound
Based on the optimal reaction conditions (example 20), the inventors further investigated the adaptability of the optimal reaction conditions to the substrate, that is, only the kind of the reaction substrate is changed, and prepared a series of 3-chloroacrylate compounds according to the reaction conditions of example 20, with the following results:
Figure BDA0003353039720000071
bthe dosage of the cyclopropenone raw material is 1g, and the dosage proportion of other reagents is the same as that of the example 20.
Figure BDA0003353039720000072
The structure of the target products 1 b-2 b,4 b-17 b is characterized:
compound 1 b:
Figure BDA0003353039720000073
IR:2940,1729,1233,692,563cm-1.1H NMR(500MHz,Chloroform-d)δ7.31–7.26(m,2H),7.23–7.13(m,8H),5.06–5.01(m,1H),3.99-3.93(m,1H),2.26–2.23(m,2H),1.80–1.71(m,3H),1.53–1.42(m,2H),1.35–1.29(m,1H).13C NMR(125MHz,Chloroform-d)δ166.4,136.7,134.4,133.7,133.2,129.6,129.2,129.0,128.3,128.1,128.0,60.0,34.6,30.1,24.2,23.0.HRMS:(ESI)calculated for C21H21Cl2O2[M+H]+375.0913,found 375.0915.。
compound 2 b:
Figure BDA0003353039720000081
IR:2965,1725,1173,692,567cm-1.1H NMR(400MHz,Chloroform-d)δ7.25–7.23(m,2H),7.24–7.15(m,6H),7.15–7.06(m,2H),4.43(t,J＝6.0Hz,2H),3.59(t,J＝6.4Hz,2H),2.20–2.14(m,2H).13C NMR(125MHz,Chloroform-d)δ167.2,136.5,134.4,133.6,133.4,129.6,129.1,129.0,128.4,128.2,128.1,62.2,41.1,31.5.HRMS:(ESI)calculated for C18H17Cl2O2[M+H]+335.0600,found 335.0605.。
compound 4 b:
Figure BDA0003353039720000082
IR:2960,1725,1504,1158,558cm-1.1H NMR(500MHz,Chloroform-d)δ7.25–7.21(m,2H),7.11–7.07(m,2H),6.93–6.88(m,4H),4.32(t,J＝5.8Hz,2H),3.55(t,J＝5.9Hz,2H),1.92–1.81(m,4H).13C NMR(125MHz,Chloroform-d)δ167.0,163.6(J＝45Hz),161.6(J＝45Hz),132.6(J＝41.2Hz),132.6(J＝41.2Hz),131.5(J＝7.5Hz),130.9(J＝8.8Hz),130.4(J＝3.8Hz),115.6(J＝42.5Hz),115.4(J＝42.5Hz),64.9,44.2,29.0,25.9.19F NMR(471MHz,Chloroform-d)δ-110.5,-112.2.HRMS:(ESI)calculated for C19H17Cl2F2O2[M+H]+385.0568,found 385.0570.。
compound 5 b:
Figure BDA0003353039720000091
IR:2958,1724,1175,740,412cm-1.1H NMR(400MHz,Chloroform-d)δ7.43–7.39(m,4H),7.19–7.15(m,2H),7.05–7.02(m,2H),4.38–4.34(m,2H),3.63–3.58(m,2H),1.96–1.90(m,4H).13C NMR(125MHz,Chloroform-d)δ166.6,135.1,133.0,131.9,131.5,131.0,130.5,123.7,122.8,65.0,44.2,29.0,25.9.HRMS:(ESI)calculated for C19H17Br2Cl2O2[M+H]+504.8967,found 504.8961.。
compound 6 b:
Figure BDA0003353039720000092
IR:2958,1724,1171,785,500cm-1.1H NMR(400MHz,Chloroform-d)δ7.24–7.19(m,2H),7.06–7.04(m,6H),4.42–4.29(m,2H),3.62–3.57(m,2H),2.35–2.31(m,6H),1.96–1.90(m,4H).13C NMR(125MHz,Chloroform-d)δ167.6,139.0,137.9,133.7,131.7,129.4,129.1,128.7,64.6,44.3,29.0,25.9,21.1.HRMS:(ESI)calculated for C21H23Cl2O2[M+H]+377.1070,found 377.1072.。
compound 7 b:
Figure BDA0003353039720000101
IR:2961,1727,1177,820,560cm-1.1H NMR(400MHz,Chloroform-d)δ7.29–7.23(m,6H),7.12–7.06(m,2H),4.40–4.36(m,2H),3.62–3.58(m,2H),1.96–1.92(m,4H),1.34–1.30(m,18H).13C NMR(125MHz,Chloroform-d)δ167.7,152.2,151.1,133.0,129.3,128.6,125.3,124.9,64.6,44.3,34.6,34.5,31.1,31.1,29.1,26.0.HRMS:(ESI)calculated for C27H35Cl2O2[M+H]+461.2009,found461.2008.。
compound 8 b:
Figure BDA0003353039720000102
IR:2958,1727,1179,686,433cm-1.1H NMR(400MHz,Chloroform-d)δ7.48–7.47(m,1H),7.44–7.33(m,2H),7.32-7.31(m,1H),7.12–7.04(m,3H),7.03–6.99(m,1H),4.32(t,J＝5.8Hz,2H),3.58–3.52(m,2H),1.90–1.86(m,4H).13C NMR(125MHz,Chloroform-d)δ166.4,138.0,136.0,133.1,133.0,132.5,132.4,131.7,131.6,130.1,129.7,128.1,127.8,122.5,122.2,65.1,44.3,29.0,25.9.HRMS:(ESI)calculated for C19H17Cl4O2[M+H]+416.9977,found416.9976.。
compound 9 b:
Figure BDA0003353039720000103
IR:2971,1723,1140,754,447cm-1.1H NMR(500MHz,Chloroform-d)δ4.24(t,J＝6.3Hz,2H),3.45(t,J＝6.6Hz,2H),2.54(q,J＝7.4Hz,2H),2.34(q,J＝7.6Hz,2H),2.03–1.98(m,2H),1.91–1.84(m,2H),1.16(t,J＝7.4Hz,3H),1.07(t,J＝7.6Hz,3H).13C NMR(125MHz,Chloroform-d)δ168.6,135.3,127.9,63.9,32.9,30.5,29.3,27.2,24.6,13.0,13.0.HRMS:(ESI)calculated for C11H19Cl2O2[M+H]+253.0757,found 253.0759.。
compound 10 b:
Figure BDA0003353039720000111
IR:2958,1725,1272,1148,652cm-1.1H NMR(500MHz,Chloroform-d)δ4.23(t,J＝5.9Hz,2H),3.58(t,J＝6.2Hz,2H),2.43–2.37(m,2H),2.35–2.28(m,2H),1.93–1.83(m,4H),1.62-1.55(m,2H),1.42-1.30(m,8H),0.96–0.89(m,6H).13C NMR(125MHz,Chloroform-d)δ168.2,135.4,131.3,69.9,63.9,44.3,34.9,30.6,29.5,29.2,27.0,26.0,22.2,22.0,13.8.HRMS:(ESI)calculated for C15H27Cl2O2[M+H]+309.1383,found 309.1383.。
compound 11 b:
Figure BDA0003353039720000112
IR:2959,1725,1176,815,579cm-1.1H NMR(500MHz,Chloroform-d)δ7.27–7.23(m,2H),6.90–6.86(m,2H),6.53(s,1H),4.35–4.32(m,2H),3.81(s,3H),3.57–3.55(m,2H),1.91-1.87(m,4H).13C NMR(125MHz,Chloroform-d)δ166.1,160.1,137.2,128.0,126.6,119.4,114.2,64.6,55.3,44.3,29.1,26.0.HRMS:(ESI)calculated for C14H17Cl2O3[M+H]+303.0549,found 303.0550.。
compound 12 b:
Figure BDA0003353039720000121
IR:2959,1726,1195,807,405cm-1.1H NMR(400MHz,Chloroform-d)δ7.56–7.45(m,2H),7.23–7.16(m,2H),6.64(s,1H),4.37–4.31(m,2H),3.63–3.58(m,2H),1.90–1.87(m,4H).13C NMR(125MHz,Chloroform-d)δ165.4,136.5,133.2,131.9,128.4,123.1,122.5,64.8,44.3,29.7,29.0,25.9.HRMS:(ESI)calculated for C13H14BrCl2O2[M+H]+350.9549,found 350.9551.。
compound 13 b:
Figure BDA0003353039720000122
IR:2959,1725,1177,809,474cm-1.1H NMR(500MHz,Chloroform-d)δ7.83–7.80(m,3H),7.77-7.76(m,1H),7.51–7.49(m,2H),7.45–7.42(m,1H),6.75(s,1H),4.40–4.36(m,2H),3.57–3.54(m,2H),1.92–1.87(m,4H).13C NMR(125MHz,Chloroform-d)δ165.9,137.8,133.2,133.1,131.5,128.5,128.2,127.6,126.8,126.7,126.2,124.0,121.6,64.7,44.3,29.1,26.0.HRMS:(ESI)calculated for C17H17Cl2O2[M+H]+323.0600,found 323.0597.。
compounds 14b and 14 b':
Figure BDA0003353039720000123
IR(14b):2959,1725,1205,698,599cm-1.1H NMR(500MHz,Chloroform-d,14b)δ7.42–7.34(m,5H),4.31(t,J＝5.8Hz,2H),3.61(t,J＝5.9Hz,2H),1.98–1.88(m,7H).13C NMR(125MHz,Chloroform-d,14b)δ168.2,137.3,132.4,129.0,128.6,128.3,127.8,64.3,44.3,29.1,26.0,18.1.HRMS:(ESI,14b)calculated for C14H17Cl2O2[M+H]+287.0600,found 287.0599.IR(14b’):2924,1722,1209,691,591cm-1.1H NMR(500MHz,Chloroform-d,14b’)δ7.39–7.33(m,3H),7.29–7.26(m,2H),4.22(t,J＝4.2Hz,2H),3.53–3.47(m,2H),2.13(s,3H),1.82–1.80(m,4H).13C NMR(125MHz,Chloroform-d,14b’)δ166.7,134.8,134.3,132.7,128.7,128.6,128.3,64.4,44.3,29.0,25.9,23.7.HRMS:(ESI,14b’)calculated for C14H17Cl2O2[M+H]+287.0600,found 287.0599.。
compounds 15b and 15 b':
Figure BDA0003353039720000131
IR:2965,1724,1265,697,592cm-1.1H NMR(500MHz,Chloroform-d)δ7.41-7.34(m,4H),7.29–7.28(m,1H),4.32(t,J＝5.8Hz,1H),4.20(t,J＝5.5Hz,1H),3.61(t,J＝5.9Hz,1H),3.49(t,J＝5.7Hz,1H),2.73-2.65(m,1H),1.99–1.89(m,3H),1.82–1.78(m,1H),1.10–1.06(m,6H).13C NMR(125MHz,Chloroform-d)δ167.2,139.4,136.9,128.9,128.6,128.5,128.5,128.4,128.2,64.3,64.2,44.3,44.3,32.2,31.0,29.2,29.0,26.1,25.9,21.3,20.4.HRMS:(ESI)calculated for C16H21Cl2O2[M+H]+315.0913,found 315.0908.。
compound 16 b:
Figure BDA0003353039720000132
IR:2955,1723,1186,722,693cm-1.1H NMR(500MHz,Chloroform-d)δ7.27–7.25(m,2H),7.23–7.17(m,6H),7.13–7.11(m,2H),4.29(t,J＝6.5Hz,2H),3.51(t,J＝6.6Hz,2H),1.82–1.72(m,4H),1.56–1.47(m,2H).13C NMR(125MHz,Chloroform-d)δ167.3,136.6,134.6,133.7,133.2,129.5,129.0,129.0,128.4,128.1,128.0,65.3,44.6,32.0,27.8,23.3.HRMS:(ESI)calculated for C20H21Cl2O2[M+H]+363.0913,found 363.0916.。
compound 17 b:
Figure BDA0003353039720000133
IR:2936,1724,1175,722,693cm-1.1H NMR(400MHz,Chloroform-d)δ7.26–7.14(m,8H),7.13–7.07(m,2H),4.27(t,J＝6.5Hz,2H),3.49(t,J＝6.6Hz,2H),1.78-1.69(m,4H),1.47–1.35(m,4H).13C NMR(125MHz,Chloroform-d)δ167.4,136.6,134.6,133.8,133.1,129.6,129.0,129.0,128.4,128.1,128.0,65.5,44.8,32.4,28.3,26.4,25.2.HRMS:(ESI)calculated for C21H23Cl2O2[M+H]+377.1070,found 377.1075.。
the embodiments described above are only preferred embodiments of the invention and are not exhaustive of the possible implementations of the invention. Any obvious modifications to the above would be obvious to those of ordinary skill in the art, but would not bring the invention so modified beyond the spirit and scope of the present invention.

Claims (10)

1. A ring-opening double-chlorination reaction method of cyclopropenone and an oxygen heterocyclic compound is characterized by comprising the following steps:
cyclopropenone compound shown as formula 1, oxacyclo compound shown as formula 2 and CuCl2Adding the auxiliary agent and the organic solvent into a reactor with a stirrer in sequence, then stirring the reaction mixture to react under the condition of inert atmosphere at 60-150 ℃, and carrying out post-treatment after the reaction is completed to obtain a 3-chloroacrylate compound shown in a formula b; the reaction formula is as follows:
Figure FDA0003353039710000011
in the above reaction formula, R1,R2Independently of one another, from hydrogen, C1-20Alkyl radical, C1-20Haloalkyl, C6-20Aryl, substituted C6-20An aryl group; provided that R is1,R2Not simultaneously selected from hydrogen; wherein said substituted C6-20The substituent of the aryl is selected from halogen and C1-6Alkyl radical, C1-6Alkoxy, -CN, C1-6Alkylcarbonyl group, C1-6An alkoxycarbonyl group;
n is 0,1,2,3 or 4;
R3,R4independently of one another, from hydrogen, C1-20Alkyl radical, C1-20A haloalkyl group; and/or when n is 0, R3,R4Are linked to each other to form a five-to seven-membered carbocyclic fused epoxy structure
Figure FDA0003353039710000012
Wherein the auxiliary agent is AlCl3、NbCl5、CoCl2、ZnCl2Any one or more of them.
2. The reaction process of claim 1, wherein R is1,R2Independently of one another, from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, trifluoromethyl, trichloromethyl, phenyl, naphthyl, anthracenyl, substituted phenyl, substituted naphthyl, substituted anthracenyl; provided that R is1,R2Not simultaneously selected from hydrogen; wherein the substituents in said substituted are selected from the group consisting of fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, methoxy, ethoxy, tert-butoxy, -CN, acetyl, methoxycarbonyl, ethoxycarbonyl;
n is 0,1,2,3 or 4;
R3,R4independently of one another, from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, trifluoromethyl, trichloromethyl; and/or when n is 0, R3,R4Are linked to each other to form a saturated five-to seven-membered carbocyclic fused epoxy structure
Figure FDA0003353039710000021
3. The reaction process of claim 2, wherein R is1,R2Independently of one another, from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, phenyl or substituted phenyl; provided that R is1,R2Not simultaneously selected from hydrogen; wherein the substituents in said substituted are selected from the group consisting of fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, methoxy, ethoxy, tert-butoxy, -CN, acetyl, methoxycarbonyl, ethoxycarbonyl;
n is 0,1,2,3 or 4;
R3,R4independently of one another, from hydrogen, methyl; and/or when n is 0, R3,R4Are connected with each other to form
Figure FDA0003353039710000022
A structure wherein m is 1,2 or 3.
4. The method of any one of claims 1 to 3, wherein the auxiliary agent is AlCl3。
5. A process according to any one of claims 1 to 3, wherein the organic solvent is acetonitrile.
6. The process according to any one of claims 1 to 3, wherein the reaction temperature is 80 to 120 ℃, preferably 100 ℃ to 120 ℃, most preferably 120 ℃.
7. The method according to any one of claims 1 to 3, wherein the reaction time of the stirring reaction is 4 to 48 hours, preferably 8 to 24 hours, and more preferably 10 to 12 hours.
8. The method according to any one of claims 1 to 3, wherein the cyclopropenone compound of formula 1, the oxacyclic compound of formula 2, CuCl2The feeding molar ratio of the auxiliary agent is 1 (1-3) to (1-5) to (0.1-0.5); preferably, the cyclopropenone compound shown in formula 1, the oxacyclo compound shown in formula 2 and CuCl2The feeding molar ratio of the auxiliary agent is 1:1.5:2: 0.3.
9. A method according to any one of claims 1 to 3, characterized in that the inert atmosphere is a nitrogen atmosphere and/or an argon atmosphere, preferably a nitrogen atmosphere.
10. A method according to any one of claims 1-3, characterized in that the post-processing operation is as follows: after the reaction is completed, adding water into the reaction mixture for quenching, adding ethyl acetate for extraction, drying the organic phase, filtering and concentrating under reduced pressure to obtain a residue, and separating the residue by silica gel column chromatography to obtain the 3-chloroacrylate compound shown in formula 3.
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