AU637647B2 – Method for the preparation of alpha, beta -unsaturated ketones
– Google Patents
AU637647B2 – Method for the preparation of alpha, beta -unsaturated ketones
– Google Patents
Method for the preparation of alpha, beta -unsaturated ketones
Info
Publication number
AU637647B2
AU637647B2
AU66424/90A
AU6642490A
AU637647B2
AU 637647 B2
AU637647 B2
AU 637647B2
AU 66424/90 A
AU66424/90 A
AU 66424/90A
AU 6642490 A
AU6642490 A
AU 6642490A
AU 637647 B2
AU637647 B2
AU 637647B2
Authority
AU
Australia
Prior art keywords
preparation
group
unsaturated ketones
electron donative
substituents
Prior art date
1989-11-17
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
AU66424/90A
Other versions
AU6642490A
(en
Inventor
Tadashi Kyotani
Masashi Nakajima
Keiichi Tsukashima
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nippon Soda Co Ltd
Original Assignee
Nippon Soda Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
1989-11-17
Filing date
1990-11-15
Publication date
1993-06-03
1990-11-15
Application filed by Nippon Soda Co Ltd
filed
Critical
Nippon Soda Co Ltd
1991-06-13
Publication of AU6642490A
publication
Critical
patent/AU6642490A/en
1993-06-03
Application granted
granted
Critical
1993-06-03
Publication of AU637647B2
publication
Critical
patent/AU637647B2/en
2010-11-15
Anticipated expiration
legal-status
Critical
Status
Ceased
legal-status
Critical
Current
Links
Espacenet
Global Dossier
Discuss
Classifications
C—CHEMISTRY; METALLURGY
C07—ORGANIC CHEMISTRY
C07D—HETEROCYCLIC COMPOUNDS
C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
C07D213/46—Oxygen atoms
C07D213/50—Ketonic radicals
C—CHEMISTRY; METALLURGY
C07—ORGANIC CHEMISTRY
C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
C07C221/00—Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
C—CHEMISTRY; METALLURGY
C07—ORGANIC CHEMISTRY
C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
C07C45/74—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups combined with dehydration
Description
Description
Method for the preparation of a , /3-unsaturated ketones
Technical Field:
This invention relates to a method for the preparation of a , β-unsaturated ketones represented by general formula (II)
(where R is a heterocyclic group with nitrogen atom in the ring or a phenyl group with electron donative substituents) (hereinafter referred to as Compound II). Compound (II) is extremely important as an intermediate for pharmaceuticals and agricultural chemicals.
Background Art:
Conventionally known methods for the preparation of Comound I include a synthetic method by aldol condensation of aldehyde and acetone (described in such documents as Ber. 353569 (1902)) and a method that aldehyde and acetoacetate are Knovenagel condensed, hydrolyzed and decarboxylated (described in such documents as J. Org. Chem. 22 1451 (1957) 3 . The methods are not applicable to industrial manufacturing since the yield is generally low.
An object of this invention is to provide methods for the preparation of a , β -unsaturated ketones which are excellent as industrial manufacturing methods.
Disclosure of Invention:
The inventors carried out varaious studies to accomplish the above purpose, and found that Coumpound (II) can be obtained with good yield by reacting specific
aldehydes with acetone, in a water solvent, using specific catalysts, while heating, and thus have accomplished this invention.
That is, this invention is a method for the preparation of a , β-unsaturated ketones represented by general formula (II)
(where R is a heterocyclic group with nitrogen atom in the ring or a phenyl group with electron donative substituents) which comprises reacting aldehydes represented by general formula (I)
RCHO (I)
(where R is as defined above) with acetone, in the presence as a catalyst of one or two or more compounds selected from the group consisting of perhydroisoindole and pyrrolidine which may have substituents, in a water solvent, at 20°C to 40°C, and
« then reacting at the reflux temperature.
Aldehydes represented by general formula (I)
RCHO (I)
(where R is as defined above) (hereinafter referred to as Compound II) and used in this invention include benzaldehydes with electron donative substituents such as p- (N,N-dimethylamino) benzaldehyde and 2,4, 6-trimethylbenzaldehyde. and heterocyclic aldehydes with nirogen atom in the ring such as 2-pyridine carbaldehyde, 3-pyridine carbaldehyde and 4-pyridine carbaldehyde.
Compounds used as catalyst include perhydroisoindole and pyrrolidine represented by the following formula which may be substituted.
(where Ri, R2, R3 and R . are hydrogen or lower al iphatic groups).
Their concrete examp les are pyrrol idine and pyrrol idines subst i tuted at the 3 and/or 4 pos i t i ons such as 3-methy l pyrro l ϊ d ine, 3-e thy l pyrro l i d i ne, 3, 3-
diraethylpyrrolidine, 3, 3-diethylρyrrolidine, 3, 4-dimethylpyrrolidine and 3,4- dϊethylpyrrolidine.
Two or more of these catalysts can be used by mixing. Water is indispensable as a catalyst. A reaction in an organic solvent results in extremely low yield.
(1) RCHO + CH»CCHs ^ RCHCH2CCH3
II I II
0 OH 0
(2) RCHCH2CCH3 ~∑∑L RCH=CHCCH3 + H20
I II II
OH 0 0
The reaction proceeds according to the above reaction equations (1) and (2). If R is a heterocyclic group containing N in the ring such as pyridyl group, Reaction (2) proceeds more, and , β-unsaturated ketones are formed from β – hydroxyketones during the addition reaction or post treatment. Therefore, it is difficult to isolate £-hydroxyketones. , β-unsaturated ketones may be formed by addition reaction at room temperature followed by dehydration with strong acid. However it is rather preferable to convert from S-hydroxyketones to a , β – unsaturated ketones by heating during the addition reaction.
If R is a phenyl group with electron donative substituents such as N- dimethylamino group or trimethyl group, the equilibrium of (1) shifts to the aldehyde side, and the reaction does not proceed. Therefore Rection (2) is advanced by heating and the equilibrium is shifted to synthesize a , #-unsaturated ketones.
A way of implementing the preparation method for compound I is described in detail in the following.
1.5 to 20 times moles, preferably 3 to 10 times moles, to a mole of Compound II, of acetone; 50 to 2000ml, prefeerably 200 to 500ml, to a mole of Compound II, of water; and 0.002 to 0.1 moles, preferably 0.01 to 0.05 moles, to a mole of Compound II, of catalyst are mixed. Into the resulting mixture is dropped a mole of Compound II at 20 to 40°C over 0.5 to 5 hours, then the mixture is kept stirring under reflux for 0.5 to 7 hours.
After the reaction is completed, the reaction solution is neutralized with acid such as hydrochloric acid to pH 1 to 6, acetone is distilled and recovered. Then the residue is extracted with water-insoluble organic solvent such as chloroform or toluene. The extract is concentrated and distilled under vacuum to give the intended Compound I.
Best Mode for carrying Out the Invention:
This invention is further described in detail by reference to the following examples. The range of this invention is not limited at all by the following examples.
Example 1
Into a reaction vessel of li in inside volume were placed 290.5g (5 moles) of acetone, 300ml of water and 3.6g (0.05 moles) of pyrrolidine, to which 149.2g (1 mole) of p-(N,N-dimethylamino) benzaldehyde was dropped over an hour while keeping at 30 °C. Then the resulting solution was stirred under reflux for 9 hours.
The solution was neutralized with concentrated hydrochloric acid up to pH 4.5, and heated to distill up to the distillation temperature of 100 °C. Then 300ml of chloroform was added, and the solution was neutralized with 28% NaOH aqueous solution to pH 12 and separated.
Furthermore, the aqueous layer was extracted with 200ml of chloroform twice. The obtained chloroform layers were combined to the previous chloroform layer to concentrate. The obtained crystal was recrystal1ized from a mixture solvent of benzene and hexane to give 113.6g (crude yield: 60.0%) of yellow crystal with melting point of 137.5 to 140.5 °C.
The crystal was analyzed by gas chromatography to find that the intended product, 4- (ρ-(N,N-dimethylamino) phenyl) -3-butene-2-one, was 97.8% in purity. (Yield: 58.7% to ρ-(N,N-dimethylamino) benzaldehyde)
Example 2
Into a reaction vessel of 300ml in inside volume were placed 87.2g (1.5 moles) of acetone, 90ml of water and 2.Og (0.02 moles) of 3, 3-dimethylpyrrolidine, to which 29.6g (0.2 mole) of 2, 4, 6-trimethylbenzaldehyde was dropped over an hour while keeping at 30 °C. Then the resulting solution was stirred under reflux for 7 hours.
The solution was adjusted the pH to 4.5 with concentrated hydrochloric acid, and heated to distill up to the distillation temperature of 100 °C. Then 80ml of chloroform was added to the resulting solution to extract and the solution was separaated. The toluene layer was concentrated. The obtained extract was distilled under reduced pressure to give distillate with boiling point of 94 to 96°C at 0.02mmHg. This distillate crystallized after the distillation to give 27. lg of yellow crystal with boiling point of 64 to 69 °C (crude yield: 72.0%).
The crystal was analyzed by gas chromatography to find that the intended product, 4-(2, 4, 6-trimethylphenyl)-3-butene-2-one, was 94.8% in purity. (Yield: 68.3% to 2,4, 6-trimethylbenzaldehyde)
Example 3
Into a reaction vessel of 1 £ in inside volume were placed 290.5g (5 moles) of acetone, 300ml of water and 3.6g (0.05 moles) of pyrrolidine, to which 107. lg (1 mole) of 3-pyridine carbaldehyde was dropped over an hour while keeping at 30°C. Then the resulting solution was stirred under reflux for 8 hours.
After the reaction was completed, concentrated hydrochloric acid was dropped to make the pH 4.5, and the solution was heated to distill up to the distillation temperature of 100°C. Then 300ml of chloroform was added, and the solution was neutralized with 28% NaOH aqueous solution to pH 12 and separated. Furthermore, the aqueous layer was extracted with 200ml of chloroform twice.
The obtained chloroform layers were combined to the previous chloroform layer to concentrate. The obtained extract was distilled under reduced pressure to give 122.8g (crude yield: 83.4%) of yellow extract with boiling point of 113. °C at
1. lmmHg and n^81.5941.
The extract was analyzed by gas chromatography to find that the intended product, 4-(3-ρyridyl)-3-butene-2-one, was 94.9% in purity. (Yield: 79.1% to 3- pyridine carbaldehyde)
Industrial Applicability:
This invention is to provide methods for the preparation of a, /3-unsaturated ketones having heterocyclic groups with nitrogen atom in the ring or phenyl groups with electron donative substituents, which are difficult to synthesize, from corresponding aldehydes andacetone, with good yield. The invention is greatly significant in industry.
Claims (1)
Claims
A method for the preparation of a , /5-unsaturated ketones represented by general formula (II)
(where R is a heterocyclic group with nitrogen atom in the ring or a phenyl group with electron donative substituents) which comprises reacting aldehydes represented by general formula (I)
RCHO (I)
(where R is as defined above) with acetone, in the presence as a catalyst of one or two or more compounds selected from the group consisting of perhydroisoindole and pyrrolidine which may have substituents, in a water solvent, at 20°C to 40°C, and then reacting at the reflux temperature.
(2) A preparation method according to Claim (1) in which the heterocyclic group with nitrogen atom in the ring is a pyridyl group.
(3) A preparation method according to Claim (1) in which the electron donative substituent is an N-dimethylamino group.
(4) A preparation method according to Claim (1) in which the electron donative substituent is a trimethyl group.
AU66424/90A
1989-11-17
1990-11-15
Method for the preparation of alpha, beta -unsaturated ketones
Ceased
AU637647B2
(en)
Applications Claiming Priority (2)
Application Number
Priority Date
Filing Date
Title
JP1297388A
JP2789735B2
(en)
1989-11-17
1989-11-17
Production of α, β-unsaturated ketones
JP1-297388
1989-11-17
Publications (2)
Publication Number
Publication Date
AU6642490A
AU6642490A
(en)
1991-06-13
AU637647B2
true
AU637647B2
(en)
1993-06-03
Family
ID=17845844
Family Applications (1)
Application Number
Title
Priority Date
Filing Date
AU66424/90A
Ceased
AU637647B2
(en)
1989-11-17
1990-11-15
Method for the preparation of alpha, beta -unsaturated ketones
Country Status (8)
Country
Link
US
(1)
US5214151A
(en)
EP
(1)
EP0457912A1
(en)
JP
(1)
JP2789735B2
(en)
KR
(1)
KR920701107A
(en)
AU
(1)
AU637647B2
(en)
BR
(1)
BR9007031A
(en)
CA
(1)
CA2044603A1
(en)
WO
(1)
WO1991007371A1
(en)
Families Citing this family (6)
* Cited by examiner, † Cited by third party
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Priority date
Publication date
Assignee
Title
BE1009764A3
(en)
*
1995-11-06
1997-08-05
Dsm Nv
Process for the preparation of alpha-alkylkaneelaldehyde.
US5861538A
(en)
*
1997-08-04
1999-01-19
Albemarle Corporation
Production of alkoxynaphthyl-substituted ketones from naphthaldehydes
DE19959053A1
(en)
*
1999-12-07
2001-06-13
Basf Ag
Process for the preparation of ketones, in particular 6-methylheptan-2-one
ATE330927T1
(en)
*
2000-08-02
2006-07-15
Astrazeneca Ab
METHOD FOR PRODUCING ALPHA-BETA UNSATURATED KETONES
DE60131660D1
(en)
2000-08-02
2008-01-10
Astrazeneca Ab
PROCESS FOR THE ASYMETRIC SYNTHESIS OF SUBSTITUTED 1,4-DIHYDROPYRIDINE DERIVATIVES
CN105152830B
(en)
*
2015-09-15
2016-09-28
河南师范大学
A kind of synthetic method of ketone compounds
Citations (3)
* Cited by examiner, † Cited by third party
Publication number
Priority date
Publication date
Assignee
Title
AU6640990A
(en)
*
1989-11-17
1991-06-13
Nippon Soda Co., Ltd.
Preparation method for alpha,beta-unsaturated ketones
AU6640590A
(en)
*
1989-11-17
1991-06-13
Nippon Soda Co., Ltd.
Method for the preparation of beta-hydroxyketones
AU6642590A
(en)
*
1989-11-17
1991-06-13
Nippon Soda Co., Ltd.
A method for the synthesis of alpha, beta -unsaturated ketones
Family Cites Families (6)
* Cited by examiner, † Cited by third party
Publication number
Priority date
Publication date
Assignee
Title
NL52433C
(en)
*
1937-11-29
FR1530436A
(en)
*
1966-04-18
1968-06-28
Firmenich & Cie
Flavoring agents
US3637712A
(en)
*
1970-01-26
1972-01-25
Bristol Myers Co
Piperidylpropanol compounds
GB2124198A
(en)
*
1982-06-18
1984-02-15
Ici Plc
Plant growth regulating method
CA1292747C
(en)
*
1983-11-21
1991-12-03
John Robert Carson
Aralykyl (arylethynyl) aralkyl amines and their use as vasodilators and antihypertensives
US4945184A
(en)
*
1989-06-19
1990-07-31
Aristech Chemical Corporation
Preparation of unsaturated ketones
1989
1989-11-17
JP
JP1297388A
patent/JP2789735B2/en
not_active
Expired – Fee Related
1990
1990-11-15
US
US07/730,843
patent/US5214151A/en
not_active
Expired – Fee Related
1990-11-15
EP
EP90916814A
patent/EP0457912A1/en
not_active
Withdrawn
1990-11-15
KR
KR1019910700749A
patent/KR920701107A/en
not_active
Application Discontinuation
1990-11-15
AU
AU66424/90A
patent/AU637647B2/en
not_active
Ceased
1990-11-15
CA
CA002044603A
patent/CA2044603A1/en
not_active
Abandoned
1990-11-15
WO
PCT/JP1990/001488
patent/WO1991007371A1/en
not_active
Application Discontinuation
1990-11-15
BR
BR909007031A
patent/BR9007031A/en
not_active
Application Discontinuation
Patent Citations (3)
* Cited by examiner, † Cited by third party
Publication number
Priority date
Publication date
Assignee
Title
AU6640990A
(en)
*
1989-11-17
1991-06-13
Nippon Soda Co., Ltd.
Preparation method for alpha,beta-unsaturated ketones
AU6640590A
(en)
*
1989-11-17
1991-06-13
Nippon Soda Co., Ltd.
Method for the preparation of beta-hydroxyketones
AU6642590A
(en)
*
1989-11-17
1991-06-13
Nippon Soda Co., Ltd.
A method for the synthesis of alpha, beta -unsaturated ketones
Also Published As
Publication number
Publication date
JP2789735B2
(en)
1998-08-20
US5214151A
(en)
1993-05-25
WO1991007371A1
(en)
1991-05-30
KR920701107A
(en)
1992-08-11
AU6642490A
(en)
1991-06-13
EP0457912A1
(en)
1991-11-27
CA2044603A1
(en)
1991-05-18
BR9007031A
(en)
1991-12-24
JPH03161458A
(en)
1991-07-11
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