CN102146028B - Method for synthesizing multiple substituted 3-alkyl four-membered cyclopentenone compounds - Google Patents
Method for synthesizing multiple substituted 3-alkyl four-membered cyclopentenone compounds Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 32
- 230000002194 synthesizing effect Effects 0.000 title abstract description 4
- BZKFMUIJRXWWQK-UHFFFAOYSA-N Cyclopentenone Chemical class O=C1CCC=C1 BZKFMUIJRXWWQK-UHFFFAOYSA-N 0.000 title abstract 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 36
- 238000006243 chemical reaction Methods 0.000 claims abstract description 25
- 239000002253 acid Substances 0.000 claims abstract description 21
- 150000002148 esters Chemical class 0.000 claims abstract description 19
- 238000011925 1,2-addition Methods 0.000 claims abstract description 5
- 238000003379 elimination reaction Methods 0.000 claims abstract description 5
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 150000002561 ketenes Chemical class 0.000 claims description 51
- 150000001336 alkenes Chemical class 0.000 claims description 20
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims description 20
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 12
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 239000011701 zinc Substances 0.000 claims description 12
- 229910052725 zinc Inorganic materials 0.000 claims description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 9
- OWQUYBAASOSGNO-CDNKMLFNSA-N 2-[[(Z)-N-(2-hydroxy-5-sulfoanilino)-C-phenylcarbonimidoyl]diazenyl]benzoic acid Chemical compound C1=CC=C(C=C1)/C(=N/NC2=C(C=CC(=C2)S(=O)(=O)O)O)/N=NC3=CC=CC=C3C(=O)O OWQUYBAASOSGNO-CDNKMLFNSA-N 0.000 claims description 8
- 229940043798 zincon Drugs 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 235000002639 sodium chloride Nutrition 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 125000000524 functional group Chemical group 0.000 claims description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 3
- 238000013019 agitation Methods 0.000 claims description 3
- 238000004440 column chromatography Methods 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 2
- 238000011068 loading method Methods 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 239000012074 organic phase Substances 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 3
- 239000002243 precursor Substances 0.000 abstract description 3
- 238000007796 conventional method Methods 0.000 abstract 1
- 230000007547 defect Effects 0.000 abstract 1
- 238000007363 ring formation reaction Methods 0.000 abstract 1
- 239000007788 liquid Substances 0.000 description 12
- 239000000758 substrate Substances 0.000 description 9
- -1 enamine salt Chemical class 0.000 description 3
- DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 2
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 229940075582 sorbic acid Drugs 0.000 description 2
- 239000004334 sorbic acid Substances 0.000 description 2
- YDRWVAFIHJGNSB-UHFFFAOYSA-N COC(=O)C(=C=C(C)C)C1=CC=CC=C1 Chemical class COC(=O)C(=C=C(C)C)C1=CC=CC=C1 YDRWVAFIHJGNSB-UHFFFAOYSA-N 0.000 description 1
- UOGPBIAJJOBXKJ-UHFFFAOYSA-N COC(C(=C=C(CCC)C)CCCC)=O Chemical class COC(C(=C=C(CCC)C)CCCC)=O UOGPBIAJJOBXKJ-UHFFFAOYSA-N 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- CSJDCSCTVDEHRN-UHFFFAOYSA-N methane;molecular oxygen Chemical compound C.O=O CSJDCSCTVDEHRN-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- IPSRAFUHLHIWAR-UHFFFAOYSA-N zinc;ethane Chemical group [Zn+2].[CH2-]C.[CH2-]C IPSRAFUHLHIWAR-UHFFFAOYSA-N 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a method for synthesizing various substituted 3-alkyl four-membered cyclopentenone compounds, i.e. a series of various substituted 3-alkyl four-membered cyclopentenone compounds are generated in one step by performing a 1,4-addition/cyclization 1,2-addition/elimination reaction of 2,3-allenoic acid ester and dialkylzinc in toluene. The method is simple to operate and has easily obtained raw materials and reagent, higher reaction yield and good region selectivity of the reaction. The defects that in the conventional method, a precursor is difficult to obtain and is unstable and the region selectivity is difficult to control are avoided. The product is easy to separate and purify. The method is suitable for synthesizing various substituted 3-alkyl four-membered cyclopentenone compounds.
Description
Technical field
The present invention relates to a kind of method of 3-alkyl tetra-atomic ring ketene compounds of synthetic various replacements, promptly by 2,3-connection olefin(e) acid ester and dialkyl group zinc take place 1 in toluene or dimethylbenzene, 4-addition/cyclisation 1,2-addition/elimination reaction, single stage method generates the 3-alkyl tetra-atomic ring ketene compounds of a series of various replacements.
Background technology
The tetra-atomic ring ketene compounds is one of intermediate important in the organic synthesis, can be used to synthetic cyclopentanone, 1, and the Cycloene derivate of 3-conjugated diolefine, phenolic compound and a series of replacements also is a structural unit common in the natural product simultaneously.Because structure is special, in the tensile tetra-atomic ring, contain the two keys of carbon-carbon double bond and carbon oxygen simultaneously, this compounds is difficult synthetic in the document, and existing method mainly prepares by alkynes [2+2] reaction with ketenes and enamine salt.But this method has that ketenes and enamine salt precursor are difficult to preparation and unstable, regioselectivity is difficult to shortcomings such as control, has limited the synthetic development of polysubstituted tetra-atomic ring ketenes.This patent provide a kind of utilization be simple and easy to dialkyl group zinc directly and 2,3-connection olefin(e) acid ester one step of reaction obtains the method for polysubstituted 3-alkyl tetra-atomic ring ketenes.
Summary of the invention
Purpose of the present invention just provides a kind of method of effectively synthesizing the 3-alkyl tetra-atomic ring ketene compounds of various replacements under simple condition.
Specific embodiments of the present invention is as follows:
The present invention is a kind of method of synthetic polysubstituted 3-alkyl tetra-atomic ring ketene compounds, by 2, and 3-connection olefin(e) acid ester
1In toluene, take place 1 with dialkyl group zinc, 4-addition/cyclisation 1,2-addition/elimination is reacted, and generates the 3-alkyl tetra-atomic ring ketene compounds of a series of various replacements, and reaction formula is as follows:
R
1/ R
2Be H or one-level, secondary and three grades of alkyl; R
3Phenyl for alkyl, naphthyl or replacement; R
4Be one-level or secondary alkyl; Very strong connection ene compound of functional group's loading property and the dialkyl group zinc that is easy to prepare are adopted in reaction, and in 2,3,4 functional groups that introducing is different of tetra-atomic ring ketenes, the alkyl group of dialkyl group zinc is introduced in 3 of tetra-atomic ring ketenes, and 2,3-connection olefin(e) acid ester
12,4 groups be introduced in 2 and 4 of tetra-atomic ring ketenes, the steps include:
(1) under nitrogen protection, in reaction tubes, adds raw material 2,3-connection olefin(e) acid ester
1(0.4 mmole), the solvent of reaction under agitation drips the dialkyl group zincon in system, finish to place oil bath to react;
(2) treat that step (1) reacts completely after, reaction tubes is back to room temperature and is cooled to zero degree, drip 1 milliliter of saturated ammonium chloride and do the cancellation reaction, use extracted with diethyl ether, organic phase is used 5% hydrochloric acid successively, and saturated sodium bicarbonate, saturated aqueous common salt are respectively washed one time, with anhydrous sodium sulfate drying, filtration, concentrated, rapid column chromatography, obtain 3-alkyl tetra-atomic ring ketene compounds again
2
Of the present invention 2,3-connection olefin(e) acid ester
1For: 4 bit substituents are the two replacements 2 of 2,4 of alkyl, 3-connection olefin(e) acid ester
1Or replace 2 entirely, 3-connection olefin(e) acid ester
1
The temperature that places oil bath to react of the present invention is 100 degrees centigrade or 140 degrees centigrade.
Dialkyl group zincon of the present invention is the toluene solution of dialkyl group zinc (1.2 mmole), and the solvent of reaction is toluene or dimethylbenzene (5 milliliters).
Dialkyl group zincon of the present invention and 2,3-connection olefin(e) acid ester
1Equivalence ratio be 3: 1, the 3-alkyl tetra-atomic ring ketene compounds that is obtained
2Be to introduce three different substituents 2,3,4 of 3-alkyl tetra-atomic ring ketenes; The alkyl of dialkyl group zincon is incorporated into 3 of tetra-atomic ring ketenes, and 2,3-connection olefin(e) acid ester
12,4 groups be introduced in 2 and 4 of tetra-atomic ring ketenes.
The present invention relates to a kind of synthetic method of polysubstituted 3-alkyl tetra-atomic ring ketene compounds, under 100 degrees centigrade or 140 degrees centigrade, is solvent with toluene or dimethylbenzene, dialkyl group zinc and 2,3-connection olefin(e) acid ester
1Take place 1,4-addition/cyclisation 1,2-addition/elimination reaction obtains a series of 3-alkyl tetra-atomic ring ketene compounds
2Present method is simple to operate, raw material and reagent are easy to get, reaction yield is higher, the regioselectivity of reaction is fine, avoided that the traditional method precursor is not easy to obtain, instability and the unmanageable shortcoming of regioselectivity, the easily separated purifying of product is applicable to the 3-alkyl tetra-atomic ring ketene compounds that synthesizes various replacements
2
The present invention has overcome the drawback of traditional method, has following beneficial effect:
1) reaction need not catalyzer; 2) can optionally introduce different substituents 2,3,4 of tetra-atomic ring ketene compounds; 3) intermediate need not separate; 4) the easily separated purifying of product.
Innovative point of the present invention is to have developed a kind of by dialkyl group zinc and 2, the methodology of the polysubstituted 3-alkyl tetra-atomic ring ketene compounds of 3-connection olefin(e) acid ester one step preparation, and the productive rate of the corresponding polysubstituted 3-alkyl tetra-atomic ring ketene compounds of gained is 50-92%.
Embodiment
Following examples help to understand the present invention, but are not limited to content of the present invention.
Embodiment 1
Under nitrogen protection, in reaction tubes, add 2-butyl-4-propyl group-2,3-heptadienoic acid methyl esters (0.0958 gram, 0.4 mmole) and toluene (5 milliliters).Under agitation in system, drip the toluene solution (0.8 milliliter, 1.5 M, 3 equivalents, 1.2 mmoles) of zinc ethyl, finish, place 100 degrees centigrade of oil baths.Be back to room temperature and reduce to zero degree after 3 hours in reaction under 100 degrees centigrade, drip 1 milliliter of saturated ammonium chloride solution cancellation reaction, use extracted with diethyl ether, 5% hydrochloric acid, saturated sodium bicarbonate, saturated aqueous common salt are respectively washed once, anhydrous sodium sulfate drying.Filter, concentrate, rapid column chromatography gets 2-butyl-4,4-dipropyl-3-ethyl tetra-atomic ring ketenes 0.0656 gram, and productive rate is 70%, product is a liquid.
Liquid;?
1H?NMR?(300?MHz,?CDCl
3)?δ?2.45?(q,?
J?=?7.6?Hz,?2?H,?CH
2),?2.09?(t,?
J?=?7.7?Hz,?2?H,?CH
2),?1.65-1.51?(m,?2?H,?CH
2),?1.50-1.27?(m,?6?H,?3?×?CH
2),?1.26-1.13?(m,?7?H,?2?×?CH
2?+?CH
3),?0.95-0.84?(m,?9?H,?3?×?CH
3);?
13C?NMR?(CDCl
3,?75?MHz)?δ?198.9,?180.5,?146.4,?69.7,?35.9,?30.0,?22.8,?22.7,?21.5,?18.9,?14.6,?13.8,?11.3;?MS?(EI)?
m/z?(%)?236?(M
+,?2.63),?207?(100);?IR?(neat,?cm
-1)?2958,?2931,?2873,?1751,?1633,?1464,?1378,?1342,?1260,?1034;?HRMS?Calcd?for?C
16H
28O?(M
+):?236.2140,?Found:?236.2140.
Embodiment 2
Press embodiment 1 described method, different is that used substrate is: 2-butyl-4-methyl-2,3-heptadienoic acid methyl esters (0.0834 gram, 0.4 mmole), get 2-butyl-3-ethyl-4-methyl-4-propyl group tetra-atomic ring ketenes 0.0647 gram, productive rate is 78%, and product is a liquid.
1H?NMR?(300?MHz,?CDCl
3)?δ?2.58-2.36?(m,?2?H,?CH
2?),?2.07?(t,?
J?=?7.5?Hz,?2?H,?CH
2),?1.63-1.40?(m,?4?H,?2?×?CH
2),?1.39-1.16?(m,?10?H,?2?×?CH
2?+?2?×?CH
3),?0.90?(t,?
J?=?7.2?Hz,?3?H,?CH
3),?0.88?(t,?
J?=?7.4?Hz,?3?H,?CH
3);?
13C?NMR?(CDCl
3,?75?MHz)?δ?199.0,?182.0,?144.8,?65.4,?36.6,?29.9,?22.8,?22.6,?21.0,?20.3,?19.2,?14.6,?13.8,?11.5;?MS?(EI)?
m/z?(%)?208?(M
+,?3.12),?179?(100);?IR?(neat,?cm
-1)?2958,?2930,?2873,?1752,?1633,?1464,?1377;?HRMS?Calcd?for?C
14H
24O?(M
+):?208.1827,?Found:?208.1826.
Embodiment 3
Press embodiment 1 described method, different is that used substrate is: 4, and 5-dimethyl-2-butyl-2,3-Sorbic Acid methyl esters (0.0851 gram, 0.4 mmole) gets 2-butyl-3-ethyl-4-methyl-4-propyl group tetra-atomic ring ketenes 0.0671 gram, productive rate is 80%, and product is a liquid.
Liquid;?
1H?NMR?(300?MHz,?CDCl
3)?δ?2.62-2.36?(m,?2?H,?CH
2),?2.08?(t,?
J?=?7.4?Hz,?2?H,?CH
2),?1.89-1.75?(m,?1?H,?CH),?1.52-1.40?(m,?2?H,?CH
2),?1.38-1.26?(m,?2?H,?CH
2),?1.25-1.19?(m,?6?H,?2?×?CH
3),?0.99-0.87?(m,?9?H,?3?×?CH
3);?
13C?NMR?(CDCl
3,?75?MHz)?δ?198.9,?181.7,?145.3,?68.8,?31.9,?29.9,?22.8,?22.6,?21.9,?19.3,?19.1,?18.1,?13.7,?11.6;?MS?(EI)?
m/z?(%)?208?(M
+,?1.67),?193?(100);?IR?(neat,?cm
-1)?2960,?2931,?2873,?1750,?1633,?1463,?1373,?1265;?HRMS?Calcd?for?C
14H
24O?(M
+):?208.1827,?Found:?208.1827.
Embodiment 4
Press embodiment 1 described method, different is that used substrate and solvent are: 2-butyl-4,5,5-trimethylammonium-2,3-Sorbic Acid methyl esters (0.0895 gram, 0.4 mmole) and dimethylbenzene (5 milliliters), temperature of reaction is 140 degrees centigrade, get 2-butyl-3-ethyl-4-tertiary butyl-4-methyl tetra-atomic ring ketenes 0.0652 gram, productive rate is 74%, and product is a liquid.
1H?NMR?(?300?MHz,?CDCl
3)?δ?2.69-2.54?(m,?1?H,?one?proton?in?CH
2),?2.52-2.37?(m,?1?H,?one?proton?in?CH
2),?2.08?(t,?
J?=?7.5?Hz,?2?H,?CH
2),?1.53-1.41?(m,?2?H,?CH
2),?1.38-1.27?(m,?2?H,?CH
2),?1.26-1.20?(m,?6?H,?2?×?CH
3),?0.97?(s,?9?H,?C(CH
3)
3),?0.90?(t,?
J?=?7.4?Hz,?3?H,?CH
3);?
13C?NMR?(CDCl
3,?75?MHz)?δ?199.2,?181.7,?145.7,?71.5,?33.9,?29.9,?27.3,?22.8,?22.7,?22.5,?15.8,?13.8,?11.8;?MS?(EI)?
m/z?(%)?222?(M
+,?45.30),?166?(100);?IR?(neat,?cm
-1)?2960,?2873,?1749,?1632,?1466,?1396,?1373,?1364,?1267,?1115;?HRMS?Calcd?for?C
15H
26O?(M
+):?222.1984,?Found:?222.1985.
Embodiment 5
Press embodiment 1 described method, different is that used substrate is: 2-phenyl-4-methyl-2,3-pentadienoic acid methyl esters (0.0802 gram, 0.4 mmole), get 2-phenyl-3-ethyl-4,4-dimethyl tetra-atomic ring ketenes 0.0568 gram, productive rate is 72%, and product is a liquid.
1H?NMR?(300?MHz,?CDCl
3)?δ?7.68-7.60?(m,?2?H,?Ar-H),?7.42-7.33?(m,?2?H,?Ar-H),?7.32-7.25?(m,?1?H,?Ar-H),?2.83?(q,?
J?=?7.6?Hz,?2?H,?CH
2),?1.36-1.27?(m,?9?H,?3?x?CH
3);?
13C?NMR?(CDCl
3,?75?MHz)?δ?197.0,?181.8,?139.1,?130.2,?128.5,?128.1,?127.1,?63.0,?21.5,?21.0,?11.5;?MS?(EI)?
m/z?(%)?200?(M
+,?59.22),?143?(100);?IR?(neat,?cm
-1)?3056,?2959,?2865,?1755,?1630,?1596,?1493,?1460,?1447,?1379,?1362,?1342,?1298,?1275,?1175,?1137,?1086,?1067;?HRMS?Calcd?for?C
14H
16O?(M
+):?200.1201,?Found:?200.1202.
Embodiment 6
Press embodiment 1 described method, different is that used substrate is: 2-(to fluorophenyl)-4-methyl-2,3-pentadienoic acid methyl esters (0.0902 gram, 0.4 mmole), get 2-(to fluorophenyl)-3-ethyl-4,4-dimethyl tetra-atomic ring ketenes 0.0640 gram, productive rate is 72%, and product is a liquid.
1H?NMR?(300?MHz,?CDCl
3)?δ?7.69-7.59?(m,?2?H,?Ar-H),?7.11-7.01?(m,?2?H,?Ar-H),?2.81?(q,?
J?=?7.7?Hz,?2?H,?CH
2),?1.35-1.27?(m,?9?H,?3?x?CH
3);?
13C?NMR?(CDCl
3,?75?MHz)?δ?196.8,?181.2,?162.2?(d,?
J?=?247.1?Hz),?138.1,?129.0?(d,?
J?=?8.6?Hz),?126.5?(d,?
J?=?3.7?Hz),?115.6?(d,?
J?=?21.5?Hz),?63.1,?21.4,?21.0,?11.5;?
19F?NMR?(CDCl
3,?282?Hz)?δ?-111.9;?MS?(EI)?
m/z?(%)?218?(M
+,?63.87),?161?(100);?IR?(neat,?cm
-1)?2960,?2926,?2866,?1754,?1631,?1600,?1590,?1508,?1460,?1370,?1362,?1339,?1294,?1231,?1158,?1102,?1071;?HRMS?Calcd?for?C
14H
15OF?(M
+):?218.1107,?Found:?218.1106.
Embodiment 7
Press embodiment 1 described method, different is that used substrate is: 2-(1 '-naphthyl)-4-methyl-2,3-pentadienoic acid methyl esters (0.1014 gram, 0.4 mmole), get 2-(1 '-naphthyl)-3-ethyl-4,4-dimethyl tetra-atomic ring ketenes 0.0796 gram, productive rate is 79%, and product is a liquid.
1H?NMR?(300?MHz,?CDCl
3)?δ?7.94-7.88?(m,?1?H,?Ar-H),?7.87-7.79?(m,?2?H,?Ar-H),?7.56-7.42?(m,?3?H,?Ar-H),?7.41-7.35?(m,?1?H,?Ar-H),?2.71?(q,?
J?=?7.7?Hz,?2?H,?CH
2),?1.45?(s,?6?H,?2?×?CH
3),?1.19?(t,?
J?=?7.7?Hz,?3?H,?CH
3);?
13C?NMR?(CDCl
3,?75?MHz)?δ?196.6,?185.6,?141.6,?133.6,?131.0,?128.7,?128.3,?127.1,?126.6,?126.3,?126.0,?125.5,?125.2,?62.5,?21.5,?21.3,?11.5;?MS?(EI)?
m/z?(%)?250?(M
+,?57.82),?193?(100);?IR?(neat,?cm
-1)?3057,?2958,?2864,?1755,?1635,?1508,?1460,?1398,?1362,?1147;?HRMS?Calcd?for?C
18H
18O?(M
+):?250.1358,?Found:?250.1359.
Embodiment 8
Press embodiment 1 described method, different is that used substrate is: 2-butyl-2, and 3-octadienoic acid methyl esters (0.0839 gram, 0.4 mmole) gets 2,4-dibutyl-3-ethyl tetra-atomic ring ketenes 0.0416 gram, productive rate is 50%, product is a liquid.
1H?NMR?(300?MHz,?CDCl
3)?δ?3.38?(t,?
J?=?6.0?Hz,?1?H,?CH),?2.68-2.53?(m,?1?H,?one?proton?in?CH
2),?2.50-2.35?(m,?1?H,?one?proton?in?CH
2),?2.06?(t,?
J?=?7.4?Hz,?2?H,?CH
2),?1.66-1.40?(m,?4?H,?2?×?CH
2),?1.39-1.23?(m,?6?H,?3?×?CH
2),?1.19?(t,?
J?=?7.7?Hz,?3?H,?CH
3),?0.94-0.84?(m,?6?H,?2?×?CH
3);?
13C?NMR?(CDCl
3,?75?MHz)?δ?194.9,?178.0,?146.2,?60.9,?29.6,?29.3,?28.6,?22.9,?22.8,?22.5,?22.1,?13.9,?13.7,?10.8;?MS?(EI)?
m/z?(%)?208?(M
+,?9.07),?165?(100);?IR?(neat,?cm
-1)?2958,?2929,?2873,?1755,?1635,?1461,?1378;?HRMS?Calcd?for?C
14H
24O?(M
+):?208.1827,?Found:?208.1828.
Embodiment 9
Press embodiment 1 described method, different is that used substrate is: the 2-tertiary butyl-2, and 3-octadienoic acid methyl esters (0.0832 gram, 0.4 mmole) gets 4-butyl-3-ethyl-2-tertiary butyl tetra-atomic ring ketenes 0.0740 gram, and productive rate is 90%, and product is a liquid.
1H?NMR?(300?MHz,?CDCl
3)?δ?3.33?(t,?
J?=?5.9?Hz,?1?H,?CH),?2.84-2.70?(m,?1?H,?one?proton?in?CH
2),?2.52-2.37?(m,?1?H,?one?proton?in?CH
2),?1.67-1.42?(m,?2?H,?CH
2),?1.38-1.22?(m,?4?H,?2?×?CH
2),?1.19-1.11?(m,?12?H,?CH
3?+?C(CH
3)
3),?0.89?(t,?
J?=?7.1?Hz,?3?H,?CH
3);?
13C?NMR?(CDCl
3,?75?MHz)?δ?194.2,?174.5,?152.8,?60.0,?32.3,?29.1,?28.51,?28.47,?22.9,?22.0,?13.9,?11.1;?MS?(EI)?
m/z?(%)?208?(M
+,?81.27),?165?(100);?IR?(neat,?cm
-1)?2961,?2930,?2873,?1753,?1622,?1461,?1363;?HRMS?Calcd?for?C
14H
24O?(M
+):?208.1827,?Found:?208.1827.
Embodiment 10
Press embodiment 1 described method, different is that used substrate and reagent are: 2-butyl-4-methyl-2, the toluene solution of 3-heptadienoic acid methyl esters (0.0950 gram, 0.4 mmole) and di-isopropyl (1.2 milliliters, 1.0 M, 3 equivalents, 1.2 mmole), get 2-butyl-3-sec.-propyl-4,4-dipropyl tetra-atomic ring ketenes 0.0820 gram, productive rate is 82%, and product is a liquid.
1H?NMR?(300?MHz,?CDCl
3)?δ?2.80?(sep,?
J?=?7.1?Hz,?1?H,?CH),?2.11?(t,?
J?=?7.7?Hz,?2?H,?CH
2),?1.69-1.55?(m,?2?H,?CH
2),?1.54-1.38?(m,?4?H,?2?×?CH
2),?1.37-1.16?(m,?12?H),?0.95-0.82?(m,?9?H,?3?×?CH
3);?
13C?NMR?(CDCl
3,?75?MHz)?δ?198.9,?183.6,?145.9,?70.3,?36.5,?30.1,?29.3,?23.3,?22.7,?20.8,?18.9,?14.6,?13.7;?MS?(EI)?
m/z?(%)?250?(M
+,?3.42),?221?(100);?IR?(neat,?cm
-1)?2959,?2931,?2873,?1749,?1626,?1465,?1382,?1269,?1165,?1072;?HRMS?Calcd?for?C
17H
30O?(M
+):?250.2297,?Found:?250.2289.
Claims (7)
1. the method for a synthetic polysubstituted 3-alkyl tetra-atomic ring ketene compounds, it is characterized in that by 2,3-connection olefin(e) acid ester 1 and dialkyl group zinc take place 1 in toluene or dimethylbenzene, 4-addition/cyclisation 1,2-addition/elimination reaction, generate the 3-alkyl tetra-atomic ring ketene compounds of a series of various replacements, reaction formula is as follows:
R
1/ R
2Be H or one-level, secondary and three grades of alkyl; R
3Be alkyl or naphthyl; R
4Be one-level or secondary alkyl; Very strong connection ene compound of functional group's loading property and the dialkyl group zinc that is easy to prepare are adopted in reaction, at 2 of tetra-atomic ring ketenes, 3, introduce different functional groups for 4, the alkyl group of described dialkyl group zinc is introduced in 3 of tetra-atomic ring ketenes, and 2,2 of 3-connection olefin(e) acid ester 1,4 groups are introduced in 2 and 4 of tetra-atomic ring ketenes, the steps include:
(1) under nitrogen protection, in reaction tubes, add 2 of raw material 0.4 mmole, 3-connection olefin(e) acid ester 1, the solvent of reaction under agitation drips the dialkyl group zincon in system, finish to place oil bath to react;
(2) treat that step (1) reacts completely after, reaction tubes is back to room temperature and is cooled to zero degree, drip 1 milliliter of saturated ammonium chloride cancellation reaction, use extracted with diethyl ether, organic phase is used 5% hydrochloric acid successively, and saturated sodium bicarbonate, saturated aqueous common salt are respectively washed one time, with anhydrous sodium sulfate drying, filtration, concentrated, rapid column chromatography, obtain 3-alkyl tetra-atomic ring ketene compounds 2 again.
2. the method for synthetic polysubstituted 3-alkyl tetra-atomic ring ketene compounds according to claim 1 is characterized in that describedly 2, and 3-connection olefin(e) acid ester 1 is: to be that 2,4 of alkyl are two replace 2 to 4 bit substituents, 3-connection olefin(e) acid ester 1 or replace 2 entirely, 3-connection olefin(e) acid ester 1.
3. the method for synthetic polysubstituted 3-alkyl tetra-atomic ring ketene compounds according to claim 1 is characterized in that the described temperature that places oil bath to react is 100 degrees centigrade or 140 degrees centigrade.
4. the method for synthetic polysubstituted 3-alkyl tetra-atomic ring ketene compounds according to claim 1 is characterized in that the toluene solution of the dialkyl group zinc that described dialkyl group zincon is 1.2 mmoles.
5. the method for synthetic polysubstituted 3-alkyl tetra-atomic ring ketene compounds according to claim 1, the solvent that it is characterized in that described reaction is 5 milliliters a dimethylbenzene, replaces the toluene in the claim 1.
6. the method for synthetic polysubstituted 3-alkyl tetra-atomic ring ketene compounds according to claim 1 is characterized in that described dialkyl group zincon and 2, and the equivalence ratio of 3-connection olefin(e) acid ester 1 is 3: 1.
7. the method for synthetic polysubstituted 3-alkyl tetra-atomic ring ketene compounds according to claim 1 is characterized in that the 3-alkyl tetra-atomic ring ketene compounds 2 that is obtained is to introduce three different substituents 2,3,4 of 3-alkyl tetra-atomic ring ketenes; The alkyl of described dialkyl group zincon is incorporated into 3 of tetra-atomic ring ketenes, and 2,2,4 groups of 3-connection olefin(e) acid ester 1 are introduced in 2 and 4 of tetra-atomic ring ketenes.
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