CN1216844C - Efficient high-stereoselectivity synthesis process of polysubstituted 3-cyclopenten-1-one - Google Patents
Efficient high-stereoselectivity synthesis process of polysubstituted 3-cyclopenten-1-one Download PDFInfo
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- CN1216844C CN1216844C CN 01141986 CN01141986A CN1216844C CN 1216844 C CN1216844 C CN 1216844C CN 01141986 CN01141986 CN 01141986 CN 01141986 A CN01141986 A CN 01141986A CN 1216844 C CN1216844 C CN 1216844C
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- butyl lithium
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Abstract
The present invention relates to a high-efficiency high-stereoselectivity synthesis process of polysubstituted 3-cyclopentene-1-ketone, which comprises: firstly a 1, 4-diiodo-1, 3-butadiene derivative dissolved in ether or tetrahydrofuran as a solvent reacts with n-butyllithium or tert-butyllithium under low temperature, carbon monoxide is introduced, the reaction is quenched, and a pure product is obtained by extraction, washing, drying, concentration and purification. The high-efficiency high-stereoselectivity synthesis process for synthesizing polysubstituted 3-cyclopentenone from carbon monoxide is scientific and rational, and the process for synthesizing carbonyl compounds by the reaction of carbon monoxide as a raw material and organolithium compounds is one of the most direct and simplest process. Moreover, the present invention has high yield and easy purification of the product.
Description
Invention field
The field is that organic synthesis intermediate is synthetic under the present invention, the efficient highly-solid selectively synthetic method of particularly a kind of polysubstituted 3-cyclopentenes-1-ketone.
Background of invention
Polysubstituted 3-cyclopentenes-1-ketone is a kind of important organic synthesis intermediate.Because the existence of the two keys in carbonyl functional group and ring texture and 3-position utilizes 3-cyclopentenes-1-ketone derivatives as raw material, can synthesize multiple useful ring compound.Though the synthetic method of 2-cyclopentenes-1-ketone has many reports, there are deficiencies such as reaction process complexity, productive rate be low.
Summary of the invention
The objective of the invention is to utilize carbon monoxide as raw material, directly and simply with synthetic be easy to get 1,4-two iodo-1,3-butadiene derivative generation cyclisation, high yield highly-solid selectively ground synthesizes polysubstituted 3-Cyclopenteneone derivatives.
Synthetic method of synthesizing polysubstituted 3-Cyclopenteneone derivatives from carbon monoxide and the efficient highly-solid selectively of organolithium compound ground of the present invention comprises will be dissolved in 1 ether or the tetrahydrofuran solvent earlier, 4-two iodo-1, the 3-butadiene derivatives reacts with n-Butyl Lithium or tert-butyl lithium under-78 ℃ to-50 ℃ temperature, feeds carbon monoxide again.In reaction under-78 ℃ to-30 ℃ temperature after 30-60 minute, cancellation reaction, again through extraction, washing, dry, concentrate, purifying promptly gets pure product.
Wherein, described ether and tetrahydrofuran solvent are handled through anhydrous and oxygen-free; described anhydrous and oxygen-free treating processes is: adopt the general method of handling the anhydrous and oxygen-free solvent; promptly under the high pure nitrogen protection, in three mouthfuls of round-bottomed flasks being furnished with reflux condensing tube and vent piston, add solvent (ether or tetrahydrofuran (THF)), a few biscuit metal sodium and an amount of benzophenone.Reflux was distilled after 4 to 5 hours.Be stored under the nitrogen.
Described 1,4-two iodo-1,3-butadiene derivatives are according to the literature method synthetic.(document: C.Xi, S.Huo, T.H.Afifi, R.Hara, T.Takahashi, TetrahedronLett.1997,38,4099-4102.).
It is n-Butyl Lithium-hexane solution of 1.24M or 1.50M that described n-Butyl Lithium adopts concentration.
It is tert-butyl lithium-Skellysolve A solution of 1.60M that described tert-butyl lithium adopts concentration.
Described 1,4-two iodo-1,3-butadiene derivatives can be and four replace, three replace or dibasic of the same race or xenogeneic alkyl (C
1-C
12), aromatic base, substituting group such as silica-based, described alkyl (C
1-C
12) as straight chained alkyl methyl, ethyl, propyl group, butyl, octyl group, decyl etc., and branched-chain alkyl, as sec.-propyl, isobutyl-, the tertiary butyl etc.; Aromatic base comprises phenyl, substituted-phenyl, as p-methoxyphenyl, o-methyl-phenyl-, contain the heteroatoms aromatic base, as thiophene etc.; Silica-based comprise as trimethyl silicon based, triethyl is silica-based etc.
Described temperature-fall period can adopt the cryostat method, bathes as dry ice-propanone.
Described carbon monoxide can directly feed from high-purity CO steel cylinder (＞99.9%), does not measure, as long as keep bubbling in the process always; Can after feeding for some time, stop to feed, in carbon monoxide atmosphere, react for some time again.
Described cancellation reaction can be adopted saturated aqueous ammonium chloride.
Described washing of extraction liquid process comprises and washes twice with water, with the saturated common salt washing once.
Described organic phase drying process is with dry 30 minutes of anhydrous MgSO4.
Described concentration process is to adopt methods such as air distillation, underpressure distillation, as uses the Rotary Evaporators vacuum concentration.
Described purge process is to do eluent, the separation of 200-300 order silicagel column with sherwood oil.
The mol ratio of described reaction raw materials is: 1, and 4-two iodo-1,3-butadiene derivatives: n-Butyl Lithium=1.0: 2.0; Or 1,4-two iodo-1,3-butadiene derivatives: tert-butyl lithium=1.0: 4.0.
Described 1, the ratio of 4-two iodo-1,3-butadiene derivatives and solvent (ether or tetrahydrofuran (THF)) is:
1 of 1mmol, the volume of the solvent (ether or tetrahydrofuran (THF)) that 4-two iodo-1,3-butadiene derivatives use is 3mL to 6mL.
Structural formula general formula such as the I and the II of the described synthetic polysubstituted 3-cyclopentenes-1-ketone that obtains.The primitive reaction formula is as follows.
The primitive reaction formula
Efficient highly-solid selectively synthetic method from the synthetic polysubstituted 3-cyclopentenes of carbon monoxide-1-ketone of the present invention is scientific and reasonable, carbon monoxide is as raw material, it with organolithium compound reaction one of the most direct the simplest method of synthesizing carbonyl compound, the synthetic method of 2-cyclopentenes-1-ketone has many reports, but the synthetic method of 3-cyclopentenes-1-ketone, the efficient highly-solid selectively synthetic method of especially polysubstituted 3-cyclopentenes-1-ketone is report not; This method is the first of the efficient highly-solid selectively synthetic method of polysubstituted 3-cyclopentenes-1-ketone, and the productive rate height, and product is easy to purifying.
Further describe the present invention below in conjunction with embodiment
Example 1
One of I compounds (R in the structural formula
1=R
2=nPr): anti--2,3,4,5-four (n-propyl)-3-cyclopentenes-1-ketone synthetic.
Under rare gas element (as high pure nitrogen) protection; add 1mmol 4 to the Schlenk of 20mL reaction tubes (a kind of glassware of using always during the anhydrous and oxygen-free operation); 7-two iodo-5,6-two (n-propyl)-4, the ether solvent that 6-Kui diene and 5mL anhydrous and oxygen-free were handled.At first above diethyl ether solution is reduced to lesser temps (78 ℃ to-55 ℃) with cryostat (bathing as dry ice-propanone), under magnetic agitation, drip 4mmol tert-butyl lithium (1.6M, Skellysolve A solution) then.Stirring reaction fed carbon monoxide 30 minutes after 1 hour under-78 ℃ to-55 ℃ temperature.Under-78 ℃ to-30 ℃ temperature, continue stirring reaction after 30 minutes, add about 1mL saturated aqueous ammonium chloride cancellation reaction.With petroleum ether extraction three times (each 10mL).Extraction liquid washes secondary (each 10mL) with water, saturated aqueous common salt 10mL washes once.The anhydrous MgSO of organic phase
4Dry 30 minutes.Concentrate the back and make the eluent post with sherwood oil and separate (200-300 order silica gel), it is anti--2,3,4 to obtain straight product, 5-four (n-propyl)-3-cyclopentenes-1-ketone 0.228g (purity＞99%, colourless liquid).Isolated yield 91%.The nuclear-magnetism of this compound and high resolution mass spectrum data are as follows.
1H?NMR(CDCl
3，SiMe
4)δ0.79-0.91(m，12H)，1.11-1.59(m，12H)，1.90-1.97(m，2H)，2.13-2.27(m，2H)，2.76(t，J＝7.0Hz，2H).
13C?NMR(CDCl
3，SiMe
4)δ13.22，13.42，18.73，20.24，27.40，30.10，52.01，135.52，221.30.HRMS?calcd?for?C
17H
30O250.2297，found?250.2299。
Example 2
Two (R of I compounds in the structural formula
1=SiMe
3, R
2=n-Hex): anti--2,5-two (trimethyl silicon based)-3,4-two (n-hexyl)-3-cyclopentenes-1-ketone synthetic.
Synthetic route is the same substantially.This synthetic raw material diiodo-compound that sets out is 1,4-two iodo-1,4-two (trimethyl silicon based)-2,3-two (n-hexyl)-1,3-butadiene.Obtain straight product 0.319g (purity＞98%, colourless liquid).Isolated yield 81%.The part characterization data of this compound is as follows.
13C?NMR(CDCl
3，SiMe
4)δ1.03，15.65，24.24，29.59，29.93，30.93，33.33，54.75，134.94，220.79.。
Example 3
One of II compounds (R in the structural formula
1=R
2=nPr): derivative y's is synthetic.
Synthetic route is the same substantially.This synthetic raw material diiodo-compound that sets out is x.Obtain straight product 0.154g (purity＞98%, colourless liquid).Isolated yield 70%.The nuclear-magnetism of this compound and high resolution mass spectrum data are as follows.
1H?NMR(CDCl
3，SiMe
4)δ0.81(t，J＝7.8Hz，6H)，1.00-1.63(m，12H)，1.75-2.00(m，4H)，2.63(t，J＝7.0Hz，2H).
13C?NMR(CDCl
3，SiMe
4)δ13.43，18.90，21.81，23.15，30.18，53.34，134.26，221.10.HRMS?calcd?for?C
15H
24O?220.1827，found?220.1818。
Claims (9)
1, a kind of synthetic method of polysubstituted 3-Cyclopenteneone derivatives, it is characterized in that comprising and to be dissolved in 1 in ether or the tetrahydrofuran solvent earlier, 4-two iodo-1,3-butadiene derivatives react with n-Butyl Lithium or tert-butyl lithium under-78 ℃ to-50 ℃ temperature, feed carbon monoxide again.In reaction under-78 ℃ to-30 ℃ temperature after 30-60 minute, cancellation reaction, again through extraction, washing, dry, concentrate, purifying promptly gets pure product.
2, synthetic method as claimed in claim 1 is characterized in that described ether and tetrahydrofuran solvent handle through anhydrous and oxygen-free.
3, synthetic method as claimed in claim 1 is characterized in that it is n-Butyl Lithium-hexane solution of 1.24M or 1.50M that described n-Butyl Lithium adopts concentration; It is tert-butyl lithium-Skellysolve A solution of 1.60M that described tert-butyl lithium adopts concentration.
4, synthetic method as claimed in claim 1 is characterized in that describedly 1, and 4-two iodo-1,3-butadiene derivatives are four to replace, three replace or dibasic of the same race or xenogeneic C
1-C
12Alkyl, aromatic base, silica-based substituent derivative.
5, synthetic method as claimed in claim 4 is characterized in that described C
1-C
12Alkyl is methyl, ethyl, propyl group, butyl, octyl group, decyl, sec.-propyl, isobutyl-, the tertiary butyl; Described aromatic base comprises phenyl, p-methoxyphenyl, o-methyl-phenyl-, thiophene; Silica-based comprise trimethyl silicon based, triethyl is silica-based.
6, synthetic method as claimed in claim 1 is characterized in that described cancellation reaction employing saturated aqueous ammonium chloride; Described washing of extraction liquid process comprises and washes twice with water, with the saturated common salt washing once; Described organic phase drying process is with dry 30 minutes of anhydrous MgSO4; Described concentration process is to adopt the Rotary Evaporators vacuum concentration; Described purge process is to do eluent, the separation of 200-300 order silicagel column with sherwood oil.
7, synthetic method as claimed in claim 1 is characterized in that the mol ratio of described reaction raw materials is: 1, and 4-two iodo-1,3-butadiene derivatives: n-Butyl Lithium=1.0: 2.0.
8, synthetic method as claimed in claim 1, the mol ratio that it is characterized in that described reaction raw materials is 1,4-two iodo-1,3-butadiene derivatives: tert-butyl lithium=1.0: 4.0.
9, synthetic method as claimed in claim 1 is characterized in that describedly 1, and the ratio of 4-two iodo-1,3-butadiene derivatives and solvent is: 1 of 1mmol, the volume of the solvent that 4-two iodo-1,3-butadiene derivatives use is 3mL-6mL.
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