CA2343521A1 - Method for producing .gamma.,.delta.-unsaturated ketones by carroll-reaction - Google Patents
Method for producing .gamma.,.delta.-unsaturated ketones by carroll-reaction Download PDFInfo
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- CA2343521A1 CA2343521A1 CA002343521A CA2343521A CA2343521A1 CA 2343521 A1 CA2343521 A1 CA 2343521A1 CA 002343521 A CA002343521 A CA 002343521A CA 2343521 A CA2343521 A CA 2343521A CA 2343521 A1 CA2343521 A1 CA 2343521A1
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- 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
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- 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
- C07C45/673—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 change of size of the carbon skeleton
- C07C45/676—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 change of size of the carbon skeleton by elimination of carboxyl groups
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Abstract
The invention relates to a method for producing .gamma.,.delta.-unsaturated ketones of general formula (I) by reacting an acetoacetic alkyl ester with a n allyl alcohol or a propargyl alcohol of general formula (II) in which R1 can represent H or a saturated or unsaturated, branched hydrocarbon radical whic h is optionally substituted by methoxy groups and which has 1 to 33 C-atoms, a nd the dashed line can represent another bond between the C-atoms carrying the same. The reaction is carried out at temperatures ranging from 150 to 220 ~C in an optionally modified Carroll reaction, in the presence of an aluminum catalyst, and by distilling off the alkanol formed during the reaction. The inventive method is characterized in that an acetoacetic ester of general formula (III) is used as an acetoacetic alkyl ester in which R2 represents a n alkyl group with 1 to 4 C-atoms.
Description
METHOD FOR PRODUCING Y,S-UrfSATURATED
KETONES BY CARROLL-REACTION
The invention relates to an improved process for preparing y,S-unsaturated ketones, in particular ineth,ylheptenone, geranylacetone and farnesylacetone or their dihydro derivatives or geranylgeranylacetone by a Carroll reaction in the presence of aluminum catalysts.
A Carroll reaction is taken to mean the chain elongation of an allyl or propargyl alcohol with acetoacetic.esters or diketene, with formation of y,8-unsaturated ketones. It~can proceed, ,for example, according to the following reaction scheme:
aceto- ~ tauto~-OH
acetylation 0~~ meriz~ation ~O~ ~~O IOH CIO
/ /
Claisen ~ O\~ decarbox~~
rearrangement j!~ ~'I' lation OH O O
In the key step, therefore, the new acetoac:etic ester of the unsaturated alcohol, which ester is primara.ly formed from the allyl or propargyl alcohol and the acetoacetic ester or diketene, rearranges to form, in a Claisen rearrangement, the 13-keto acid, which then spontaneously decarboxylates. Initial studies on Carroll reactions are described in J. Am. C:hem. Soc. 65 (1943) 1992 - 1998.
Since the beginning of the 1950s, this reaction has been employed in various ways in terpene preparation. For example, the terpenes 2-methyl-2-hepten-6-one, 6,10-dimethyl-5,9-~undecadien-2-one (geranylacetone) and 6,10,14-trimethyl-5,9,13-penta-decatrien-2-one (farnesylacetone), which are required as essential precursors of vitamin A and vitamin E, are prepared on an industrial scale~by the Carroll reaction.
Thus, for example, GB 695 3i3 discloses Carroll reactions in the gas phase at from 300 to 600~C with the use of allyl or crotyl acetoacetate.
US 2,628,250 discloses the preparation of 2-methyl-2-hepten-6-one from 2-methyl-3-buten-2-of and diketene.
US 2,660,608 discloses the preparation of tetrahydrofarnesylacetone from tetrahydronerolidol and diketene.
As catalysts for Carroll reactions, use has been made according to the process of US 2 795 617 of aluminum alkoxides, in particular the aluminum isopropoxide of the formula A1(0-CH(CH3)2)3 in amounts of from 0.8 to 2.5 mold, based on the alcohol used as starting material.
According to the process of GB 886 353, for Carroll reactions, use has been made of aluminum complexes containing acetylacetone or acetoacetic esters, such as aluminum tri(acetylacetonate), aluminum tri(methylacetoacetate) or aluminum tri(ethylacetoacetate} as catalysts.
In the case of the previously known Carroll reactions of an acetoacetic ester with a tertiary vinylcarbinol or propargyl alcohol, generally, as alkyl acetoacetate, use was made of the methyl or ethyl esters. The low-boiling primary alcohol (methanol or ethanol) released in the acetoacetylation of the unsaturated alcohol was distilled off during the reaction together with the carbon dioxide formed in the decarboxylation.
The yields achieved in the Carroll reaction using methyl or ethyl acetoacetate are not yet completely satisfactory for use on an industrial scale. This is due firstly to the relatively long reaction times necessary and, secondly, to the fact that, under the reaction conditions, the unsaturated ketones formed are hydrogenated to a slight extent to alcohols which are difficult to remove, which impairs the yields.
It is an object of the present invention, therefore, to shorten the reaction times for preparing y,8-uns~~turated ketones by reacting allyl or propargyl alcohols with acetoacetic esters in an aluminum-catalyzed Carroll reaction a:nd thus to improve the possibility of a continuous process procedure. It is also an object of the present invention to further improve the yields.
we have found that this object is achieved by a process described at the outset. It has now surprisingly been found that when use is made of acetoacetic esters of tertiary alcohols, such as tert-butanol, tert-pentyl alcohol (2 met:hylbutan-2-ol) or dimethylpropylcarbinol (2-methylpentan-2~-ol), instead of methyl.
acetoacetate (AME) or ethyl acetoacetate, the Carroll reactions proceed to y,~-unsaturated ketones more rapidly and with higher yields, that is to say forming fewer byproducts. These improvements are particularly important .if, as starting compound, use is made of a higher, and thus more v<~luable, unsaturated alcohol. This applies especially to the use of 3,7-dimethyl-1,6-octadien-3-of (linalool;), 3,7,11-trimethyl-1,6,10-dodecatrien-3-of (nerolidol), 3,7,10-trimethyl-1,6-dodecadien-3-of (dihydrolinalool) and particularly to E,E-9,7,11,15-tetramethy:l-1,6,10,14-hexa-tetraen-3-of (E,E-geranyllinalool).
Although EP 376 859 B1 has already disclosed that, in the acetoacetylation of nucleophiles, such as alkanols, alkylamines or alkylthiols, with acetoacetic esters or their derivatives, good yields can also be achieved if, as acetoacetic esters, use is made of esters of tertiary alcohols, such as tert-butanol or tert-amyl alcohol, this does not relate t:o Carroll reactions, but to the functionalization by acetoacetylat:ion of low-molecular-weight or polymeric nucleophiles which are ultimately used as coatings to improve dyeing technology.
The invention relates to a process for preparing y,b-unsaturated ketones of the formula I
O
(I) R
by reacting an allyl alcohol or a proparc_~yl alcohol of the formula II
R1~_ (II) OH
where R1 is H or a saturated or unsaturated branched, unsubstituted or methoxy-substituted hydrocarbon radical having from 1 to 33 carbons and the dotted line can be a further bond between the carbons bearing it, with an alkyl acetoacetate at temperatures of from 150 to 220~C in an unmodified or modified Carroll reaction in the presence of an aluminum catalyst and with the alkanol which forms being distilled off, which comprises making use: of, as alkyl acetoacetate, an acetoacetic ester of the: formula III
KETONES BY CARROLL-REACTION
The invention relates to an improved process for preparing y,S-unsaturated ketones, in particular ineth,ylheptenone, geranylacetone and farnesylacetone or their dihydro derivatives or geranylgeranylacetone by a Carroll reaction in the presence of aluminum catalysts.
A Carroll reaction is taken to mean the chain elongation of an allyl or propargyl alcohol with acetoacetic.esters or diketene, with formation of y,8-unsaturated ketones. It~can proceed, ,for example, according to the following reaction scheme:
aceto- ~ tauto~-OH
acetylation 0~~ meriz~ation ~O~ ~~O IOH CIO
/ /
Claisen ~ O\~ decarbox~~
rearrangement j!~ ~'I' lation OH O O
In the key step, therefore, the new acetoac:etic ester of the unsaturated alcohol, which ester is primara.ly formed from the allyl or propargyl alcohol and the acetoacetic ester or diketene, rearranges to form, in a Claisen rearrangement, the 13-keto acid, which then spontaneously decarboxylates. Initial studies on Carroll reactions are described in J. Am. C:hem. Soc. 65 (1943) 1992 - 1998.
Since the beginning of the 1950s, this reaction has been employed in various ways in terpene preparation. For example, the terpenes 2-methyl-2-hepten-6-one, 6,10-dimethyl-5,9-~undecadien-2-one (geranylacetone) and 6,10,14-trimethyl-5,9,13-penta-decatrien-2-one (farnesylacetone), which are required as essential precursors of vitamin A and vitamin E, are prepared on an industrial scale~by the Carroll reaction.
Thus, for example, GB 695 3i3 discloses Carroll reactions in the gas phase at from 300 to 600~C with the use of allyl or crotyl acetoacetate.
US 2,628,250 discloses the preparation of 2-methyl-2-hepten-6-one from 2-methyl-3-buten-2-of and diketene.
US 2,660,608 discloses the preparation of tetrahydrofarnesylacetone from tetrahydronerolidol and diketene.
As catalysts for Carroll reactions, use has been made according to the process of US 2 795 617 of aluminum alkoxides, in particular the aluminum isopropoxide of the formula A1(0-CH(CH3)2)3 in amounts of from 0.8 to 2.5 mold, based on the alcohol used as starting material.
According to the process of GB 886 353, for Carroll reactions, use has been made of aluminum complexes containing acetylacetone or acetoacetic esters, such as aluminum tri(acetylacetonate), aluminum tri(methylacetoacetate) or aluminum tri(ethylacetoacetate} as catalysts.
In the case of the previously known Carroll reactions of an acetoacetic ester with a tertiary vinylcarbinol or propargyl alcohol, generally, as alkyl acetoacetate, use was made of the methyl or ethyl esters. The low-boiling primary alcohol (methanol or ethanol) released in the acetoacetylation of the unsaturated alcohol was distilled off during the reaction together with the carbon dioxide formed in the decarboxylation.
The yields achieved in the Carroll reaction using methyl or ethyl acetoacetate are not yet completely satisfactory for use on an industrial scale. This is due firstly to the relatively long reaction times necessary and, secondly, to the fact that, under the reaction conditions, the unsaturated ketones formed are hydrogenated to a slight extent to alcohols which are difficult to remove, which impairs the yields.
It is an object of the present invention, therefore, to shorten the reaction times for preparing y,8-uns~~turated ketones by reacting allyl or propargyl alcohols with acetoacetic esters in an aluminum-catalyzed Carroll reaction a:nd thus to improve the possibility of a continuous process procedure. It is also an object of the present invention to further improve the yields.
we have found that this object is achieved by a process described at the outset. It has now surprisingly been found that when use is made of acetoacetic esters of tertiary alcohols, such as tert-butanol, tert-pentyl alcohol (2 met:hylbutan-2-ol) or dimethylpropylcarbinol (2-methylpentan-2~-ol), instead of methyl.
acetoacetate (AME) or ethyl acetoacetate, the Carroll reactions proceed to y,~-unsaturated ketones more rapidly and with higher yields, that is to say forming fewer byproducts. These improvements are particularly important .if, as starting compound, use is made of a higher, and thus more v<~luable, unsaturated alcohol. This applies especially to the use of 3,7-dimethyl-1,6-octadien-3-of (linalool;), 3,7,11-trimethyl-1,6,10-dodecatrien-3-of (nerolidol), 3,7,10-trimethyl-1,6-dodecadien-3-of (dihydrolinalool) and particularly to E,E-9,7,11,15-tetramethy:l-1,6,10,14-hexa-tetraen-3-of (E,E-geranyllinalool).
Although EP 376 859 B1 has already disclosed that, in the acetoacetylation of nucleophiles, such as alkanols, alkylamines or alkylthiols, with acetoacetic esters or their derivatives, good yields can also be achieved if, as acetoacetic esters, use is made of esters of tertiary alcohols, such as tert-butanol or tert-amyl alcohol, this does not relate t:o Carroll reactions, but to the functionalization by acetoacetylat:ion of low-molecular-weight or polymeric nucleophiles which are ultimately used as coatings to improve dyeing technology.
The invention relates to a process for preparing y,b-unsaturated ketones of the formula I
O
(I) R
by reacting an allyl alcohol or a proparc_~yl alcohol of the formula II
R1~_ (II) OH
where R1 is H or a saturated or unsaturated branched, unsubstituted or methoxy-substituted hydrocarbon radical having from 1 to 33 carbons and the dotted line can be a further bond between the carbons bearing it, with an alkyl acetoacetate at temperatures of from 150 to 220~C in an unmodified or modified Carroll reaction in the presence of an aluminum catalyst and with the alkanol which forms being distilled off, which comprises making use: of, as alkyl acetoacetate, an acetoacetic ester of the: formula III
O
CH3 - CO - CH2 - C ~ H3 (III) r p-C- R2 where R2 is an alkyl having from 1 to 4 carbons.
Surprisingly, using the process according to the invention, the higher y,8-unsaturated ketones can be obtained in a simple manner and in a continuous process procedure, which is particularly desirable for processes on an industrial scale, in yields of from 92 to 96% of theory, even if no excess, or only a slight excess, of one of the reaction components is used. In addition, it is a great advantage that the process according to the invention can increase the space-time yields of the presviously known processes.
The process according to the invention is of particular importance for reacting alcohols of the i'ormula (II), where R1 is a group of the formula IV
CH;-f-C-CH-CH=-CH_-j- (lU), X Y
where n is an integer from 1 to 5 and x and y are either both H
or x is methoxy and y is H, or x and y together are an additional bond between the carbons bearing x and y,, such as 3,7-dimethyl-1,6-octadien-3-of (linalool;i, 3,7-dimethyl-1-octen-3-ol, 3,7,11-trimethyl-1,6,10-dodecatrien-3-of (nerolidol), 3,7,11-trimethyl-1-dodecen-3-ol, 3,7,1I-trimethyl-1,6-dodecadien-3-of (dihydronerolidol) and 3,7,11,I5-tetramethyl-1,6,10,14-(E,E)hexadecatetraen-3-of (E,E-geranyllinalool).
The use of tert-butyl or tert-amylacetoac:etate is accompanied by the advantage of a more rapid reaction and the avoidance of byproducts. The amounts of the reactants used are advantageously selected in such a manner as to give a molar ratio of alcohol of the formula II to alkyl acetoacetate of the formula III of from 0.8 to 1.2, preferably from 0.95 to 1.10"
Suitable organic aluminum compounds for the process according to the invention are essentially compounds ~of the formula V
AI _~
CH-CO-R5 ~ CH-CO-F~ ~ R-' 3-m-n m n where R4 is branched or unbranched alkyl or alkoxy having from 1 to 4 carbons, preferably methyl or ethyl, RS and R6 are branched or unbranched alkyl or alkoxy having from 1 to 5 carbons, preferably methyl or 2-butyl, R~ is a branched or unbranched alkyl having from 1 to 4 carbons and m and n can be integers from 0 to 3, where n+m ~ 3, and aluminum triarylo~s:ylates. Particular preference is given to liquid aluminum compounds, in particular aluminum compounds in which R5 is a methyl, R6 is a butyl and the sum of n+m = 3 and the ratio n/m > 0.3.
The first-mentioned catalysts are therefore lower aluminum trialkoxides, such as aluminum trimethoxide, aluminum triethoxide, aluminum triisopropoxide, aluminum tri-sec-butoxide, and compounds which are formed in the reaction of said aluminum trialkoxides with stoichiometric amounts of acetylacetonate, alkyl acetoacetate or alkyl malonate with elimination of alcohol and transesterification. Examples are aluminum triacetoacetate, aluminum triacetylacetonate, aluminum monoacetoacetate diethoxide, aluminum monoacetoacetate diisopropoxide, aluminum diacetoacetate monoisopropoxide.
Preferably, use is made of the aluminum t:rialkoxides, in particular aluminum triisopropoxide and aluminum tri-sec-butoxide. Very particularly preferably, use is made of mixed aluminum triacetoacetates which are: produced by reacting aluminum sec-butoxide or aluminum triisopropoxide with methyl acetoacetate with elimination of 2-butane>1 or isopropanol and + v crif.~..v .~...~. .~.f t ~ cthnxv Qr n " ~ c,. i th the -hpta_npl_ ,.rans~st~y at r. h.. m.. . 1 ~re..p : r_,... 2 isopropanol released, where the degree of transesterification is to be above 30%.
For the purposes of the invention, aluminum triaryloxylates are the aluminum salts of aromatic hydroxy compounds, such as aluminum triphenolate, aluminum tricresol.ates, aluminum trixylenolates, aluminum trinaphtholates, whose aryl radicals can also be substituted by lower alkyl or alk.yloxy groups, i.e. alkyl or alkyloxy groups having from 1 to 4 carbons, hydroxyl groups or 0050/49363 ~ 02343521 2001-03-05 phenyl. Particularly advantageously, of these, use is made of the relatively readily accessible aluminum triphenolate.
It is advantageous to use liquid catalysts or solutions of solid catalysts and to feed these into the reaction vessel in liquid form.~Thus, for example, use can be made of aluminum trialkoxides dissolved in alkyl acetoacetate or in a :mixture of alkyl acetoacetate and an alcohol of the formula II.
The amount of the aluminum compound is generally such that its concentration in the reaction mixture does not fall below 0.050 by weight of Al and, at the start of the reaction, does not exceed 6% by weight of A1. Based on alkyl acetoacetate to be reacted, generally from 0.5 to 5 mold of the aluminum compound are required. For the aluminum triisopro:poxide preferably used and the above-described mixed aluminum triacetoacetate prepared from aluminum sec-butoxide and methyl acetoacetate, amounts of from about 1 to 3 mold, based on the alkyl acetoacetate to be reacted, are used, for example.
When use is made of allyl alcohols of the formula II having a boiling point below 120~C, such as 2-methyl-3-buten-2-ol, it is particularly advantageous if the Carroll reaction is carried out in a cyclic carbonate of the formula VI ~or a y-lactone of the formula VII
R1 \ Rz \ / R1 /"C O, C H C
R \2 C=O C=O
R3\ ~ R3 \
~vz? ~vII~.
where the radicals R1, R2 and R3 are H, methyl or ethyl, preferably H or methyl, and R4 is H, methyl, ethyl, isopropyl, phenyl or methoxymethyl, preferably H or methyl, as solvent.
Suitable cyclic 5-member-ring carbonates of the formula VI are, in addition to the customary alkylene carbonates, such as ethylene carbonate, 1,2-propylene carbonate, isabutylene carbonate and 1,2-butylene carbonate, i.~e. carbonates of the formula VI where R1 to R4 are H or methyl., or R1 to R3 are H or methyl and R4 is ethyl, also those where R1 to R3 can additionally be ethyl and R4 is H, methyl, ethyl, isopropyl, phenyl or methoxymethyl.
The cyclic carbonates used can also be prepared extremely inexpensively industrially by reacting t:he corresponding alkylene oxides with COZ. They generally have boi:Ling points which are so high that, at atmospheric pressure, temperatures of 170~C can be reached without problems.
Particularly suitable 5-member-ring lactones of the formula VII
are y-butyrolactone and 3-methyl-y-butyrolactone, in particular y-butyrolactone.
The y-butyrolactones used according to the invention of the formula VII can also be prepared with ad~Tantage industrially by dehydrogenating the corresponding butanediols.
The alkanol formed in the reaction attaclts the cyclic carbonates or lactones, under the reaction conditions, surprisingly so little that, for example, when use is made of propylene carbonate, the solvent can be reused for up to 10 reaction cycles without any clean-up (cf. comparative example lb). The cyclic carbonate or lactone which is separated off after isolation of the y,8-unsaturated ketone can be fed into new reaction cycles without supplementing the catalyst. Residues of unreacted acetoacetate remain in the solvent and are not lost.
The 5-member-ring carbonates and 5-member-ring lactones are generally used in amounts of from 50 to :10000 by weight, preferably from 100 to 500% by weight, based on y,8-unsaturated ketone formed.
When use is made of alcohols of the formula II which have a boiling point above 140~C, the Carroll reaction can also advantageously be carried out without adding significant amounts of a solvent. This is accompanied by advantages in the workup of the reaction mixture.
The process according to the invention can be carried out batchwise and continuously. When it is carried out continuously, advantageously, the starting compounds and the catalyst are pumped into a reaction vessel which is provided with a heating bath and has an attached condensation apparatus for the alcohol which is eliminated and for discharging t:he carbon dioxide formed and the reaction product is obtained using an overflow.
Using the process according to the invention, the sought-after y,8-unsaturated ketones of the formula I can be obtained in a simple manner in surprisingly high yielda. The tertiary alcohols 0050/49363 ~ 02343521 2001-03-05 eliminated from the acetoacetic ester ca;n be recovered virtually completely.
Examples Example la Carroll reaction of 2-methyl-3-buten-2-o:1 with tert-butyl acetoacetate in propylene carbonate at 180°C
A mixture of 25.7 g of a 92~ pure 2-methyl-3-buten-2-of and 39.8 g of tert-butyl acetoacetate were [aic] added dropwise in the course of 2 hours at 170°C to a mixture of 50 ml (45 g) of 1,2-propylene carbonate and 2.8 g of a separately prepared (in accordance with GB 886 353) aluminum trimethylacetoacetate catalyst. During the dropwise addition, -there was vigorous evolution of C02 and low-boilers which were continuously distilled off (b. p. - 80-85°C). After completion of the dropwise addition, the mixture was stirred for a further 10 minutes until the completion of gas evolution and was then cooled. Then, at approximately 100 mbar, first runnings o:f 2.5 g were distilled and 30.9 g of a main fraction consisting of 96-98~ pure 2-methyl-2-hepten-6-one. The yield (together with the amount remaining in the distillation bottom phase) was 92% of theory.
Example lb (Comparative example) Reaction of 2-methyl-3-buten-2-of with methyl acetoacetate in 1,2-propylene carbonate a) A mixture of 29.03 g (0.25 mol) of methyl acetoacetate (AME;
purity 98%) and 23.68 g (0.275 mol) of 2-methyl-3-buten-2-of (MBE; purity 94%) was pumped at 180°C, with stirring, in the course of 2 hours into a mixture of 45 g of 1,2-propylene carbonate and 2.8 g of a separately prepared (according to GB
886 353) aluminum trimethylacetoacetate catalyst. During this time, C02 escaped and 8 g of low-boilers were distilled off, which low-boilers consisted of about 2/3 of methanol and about 1/3 of unreacted 2-methyl-3-buten-2-ol. The mixture was then stirred for a further 30 minutes at 180°C, and then cooled and, at a reduced pressure of 100 mbar, the desired 2-methyl-2-hepten-6-one was distilled off from the reaction mixture.
b) The distillation residue produced in this case was again admixed with the abovementioned amounts of AME and MBE at 180°C in the course of 2 h, the reaction mixture was stirred for 30 min at 180~C, then cooled and the resultant 2-methyl-2-hepten-6-one was distilled off therefrom.
c) Procedure b) was repeated a further 8 times. The mean yield of 2-methyl-2-hepten-6-one over all i0 batches was 88~ of theory, based on MBE reacted (gas-chromatographic determination using an internal standard).
Example 2a Carroll reaction of 3,7-dimethyl-1,6-octadien-3-of (linalovl) with tert-butyl acetoacetate to form 6,IO-dimethyl-5,9-undecadien-2-one 5.6 g of aluminum trimethylacetoacetate (prepared from aluminum triisopropoxide similarly to GB 886353) were charged, heated to 180~C and at this temperature in the course of 2 h a homogeneous mixture of 115.7 g of linalool and 128 g of tert-butyl acetoacetate was pumped into the reaction vessel. In the course of this there was spontaneous formation of C02 and tert-butanol, which was condensed. 51 g of tert-butanol. were isolated.
After completion of the feed, the mixture was stirred for a further 20 min at an internal temperatures of 180-190~C and was then cooled. The reaction discharge was distilled at a pressure reduced to 0.1 mbar. This produced, in two fractions, a total of 139.7 g of 6,10-dimethyl-5,9-undecadien-2-one (geranylacetone), which is equivalent to a yield of 96g of theory.
Example 2b (Comparative example) Carroll reaction of linalool with methyl acetoacetate As in Example 2a), 5.6 g of the aluminum catalyst described there were charged and a mixture of 115.4 g of linalool and 94 g of methyl acetoacetate was pumped in at an internal temperature of 180~C. In the course of this there was spontaneous formation of C02 and methanol, which was condensed. The reaction solution was, as in Example 2a), stirred for a further 20 min until cessation of the COZ evolution and was then cooled. Distillation was performed under reduced pressure, producing 133 g of geranylacetone. The yield was 91.5% of theory. As byproducts, 1.6 g of 6,10-dimethyl-5,9-undecadien-2-of were formed, which were not detectable in Example 2a). .
0050/49363 ~ 02343521 2001-03-05 Example 3a Carroll reaction of 3,7,11,15-tetramethy:l-i,6,10,14(E,E)hexadecatetraen-3-of (E,E-geranyllinalool) with 5 tert-butyl acetoacetate to form 6,10,14,:L8-tetramethyl-5,9,13,17-nonadecatetraen-2-one (geranylgeranylacei=one) 2.5 g of aluminum tri-tert-butylacetoacei~ate were dissolved at 40~C in 42.1 g of tert-butyl acetoacetate: and 72.5 g of 10 E,E-geranyllinalool were added to this ai= 20°C. This resulting mixture was pumped uniformly into a horizontal heated reaction vessel equipped with an overflow and attached distillation bridge. The feed rate was set so that the' mean residence time was 10 min. The internal temperature was 190-200°C. During the reaction, 15 g of tert-butanol distilled off.
After completion of the feed, the reaction discharge was distilled. This produced 75.9 g of geranylgeranylacetone of a purity of 98.8x. This is equivalent to a yield of 92°s of theory.
Example 3b (Comparative example) Carroll reaction of E,E-geranyllinalool with methyl acetoacetate to form geranylgeranylacetone 2.2 g of aluminum trimethylacetoacetate were dissolved at 60°C in 37.6 g of methyl acetoacetate and the so:Lution was mixed with 87 g of E,E-geranyllinalool. This solution was pumped uniformly into the horizontal reactor vessel described in Example 3a). The pumping rate was matched to the available reaction volume to give a mean residence time of 10 ~ 0.5 min. At an internal temperature of 190-200°C, the mixture reacted continously to form geranylgeranylacetone. After completion of the feed, the contents of the reactor were heated for a further 10 min and then passed to the cooled reaction discharge. Distil:Lation was performed at 0.3 mbar, producing in the main fraction 84.2 g of geranylgeranylacetone of a purity of 97.:10. This is equivalent to a yield of 85% of theory.
Example 4a Carroll reaction of nerolidol with 2-met:nylbut-2-yl acetoacetate 5.6 g of aluminum trimethylacetoacetate were charged into the same reaction vessel as described in Example 4a and heated to 190°C. A mixture of 166 g of nerolidol and 139 g of an isopentyl acetoacetate (purity > 980) prepared in .a manner known per se from isopentanol and diketene was added <iropwise uniformly in the course of 2 h. The reaction temperature was kept by heating at 190-200~C in the course of this. After completion of the feed, the mixture was stirred for a further 15 min and then cooled. This produced 212 g of crude material which was distilled at 0.1 mbar.
Two fractions gave 178.7 g of farnesylaceatone. This is equivalent to a yield of 910 of theory.
Example 4b (Comparative example) Reaction of nerolidol with methyl acetoac:etate:
5.6 g of aluminum trimethylacetoacetate were charged into a 500 ml reaction vessel equipped with a metering device, paddle agitator and a 10 cm column having attached reflux condenser and distillation bridge. The contents were hs~ated to 180-190~C. In the course of 2 h, a homogeneous mixture of 7166.5 g (0.75 mol) of nerolidol and 94 g (0.81 mol) of methyl acetoacetate was pumped in uniformly. The reaction temperature was kept to 180-190~C by external heating. The methanol formed was condensed. After completion of the feed, the mixture was stirred for a further 15 min and then cooled. This produced 20F3 g of crude material which was distilled under greatly reduced pressure. In two fractions, together, 167 g of farnesylace~tone were isolated. This is equivalent to a yield of 85% of theory.
Example 5 Carroll reaction of neralidol with 2-methyl-2-pentyl acetoacetate (isohexyl acetoacetate):
2.8 g of aluminum trimethylacetoacetate were charged into the reaction vessel described in Example 4a. At a reaction temperature of 190-200~C, in the course of 1 h, a mixture of 83 g of nerolidol and 75 g of an isohexyl acet:oacetate (purity > 984) prepared from isohexanol and diketene were pumped in. After completion of the feed, the reaction mixture was stirred for a further 10 min at 200~C and cooled after gas evolution was complete. This produced 108 g of crude material which were distilled under greatly reduced pressure.. 88 g of pure farnesylacetone were isolated in this manner. This is equivalent to a yield of 90% of theory.
Example 6 a) Inventive reaction of E,E-geranyllinalool with tert-butyl acetoacetate 263 ml of a reaction solution consisting of 145 g (0.5 mol) of E,E-geranyllinalool, 5 g of aluminum tri-tert-butyl acetoacetate and 83 g (0.525 mol) of tert-butyl acetoacetate were pumped at a rate of 5.6 ml/min into a magnetically stirred reaction vessel consisting of a 100 ml three-necked flask heated to 190 to 200°C by a heating mantle with an overflow in the center (corresponding to a usable volume of the flask of 45 ml).
This produced 185 g of crude product and 30.5 g of low boilers. The crude product comprised 13% unreacted E,E-geranyllinalool and 79% of the desired geranylgeranylacetone.
b) Reaction of E,E,-geranyllinalool [sick with methyl acetoacetate (Comparative example) 234 ml of a reaction solution consisting of 145 g (0.5 mol) of E,E-geranyllinalool, 5 g of aluminum tri-tert-butyl acetoacetate and 61 g (0.525 mol) of methyl acetoacetate were pumped at a rate of 5.0 ml/min into the abovementioned reaction vessel which was heated to 190 to 200°C.
This produced 199.9 g of crude product and 5.7 g of low boilers. The crude product comprised 53% unreacted E,E-geranyllinalool and only 34% of the desired geranylgeranylacetone.
Comparison of Example 6a with Comparative Example 6b clearly shows that the reaction with the tert-butyl acetoacetate proceeds considerably more rapidly (3 to 10 times more rapidly) than the methyl acetoacetate which has previously been customary for Carroll reactions.
CH3 - CO - CH2 - C ~ H3 (III) r p-C- R2 where R2 is an alkyl having from 1 to 4 carbons.
Surprisingly, using the process according to the invention, the higher y,8-unsaturated ketones can be obtained in a simple manner and in a continuous process procedure, which is particularly desirable for processes on an industrial scale, in yields of from 92 to 96% of theory, even if no excess, or only a slight excess, of one of the reaction components is used. In addition, it is a great advantage that the process according to the invention can increase the space-time yields of the presviously known processes.
The process according to the invention is of particular importance for reacting alcohols of the i'ormula (II), where R1 is a group of the formula IV
CH;-f-C-CH-CH=-CH_-j- (lU), X Y
where n is an integer from 1 to 5 and x and y are either both H
or x is methoxy and y is H, or x and y together are an additional bond between the carbons bearing x and y,, such as 3,7-dimethyl-1,6-octadien-3-of (linalool;i, 3,7-dimethyl-1-octen-3-ol, 3,7,11-trimethyl-1,6,10-dodecatrien-3-of (nerolidol), 3,7,11-trimethyl-1-dodecen-3-ol, 3,7,1I-trimethyl-1,6-dodecadien-3-of (dihydronerolidol) and 3,7,11,I5-tetramethyl-1,6,10,14-(E,E)hexadecatetraen-3-of (E,E-geranyllinalool).
The use of tert-butyl or tert-amylacetoac:etate is accompanied by the advantage of a more rapid reaction and the avoidance of byproducts. The amounts of the reactants used are advantageously selected in such a manner as to give a molar ratio of alcohol of the formula II to alkyl acetoacetate of the formula III of from 0.8 to 1.2, preferably from 0.95 to 1.10"
Suitable organic aluminum compounds for the process according to the invention are essentially compounds ~of the formula V
AI _~
CH-CO-R5 ~ CH-CO-F~ ~ R-' 3-m-n m n where R4 is branched or unbranched alkyl or alkoxy having from 1 to 4 carbons, preferably methyl or ethyl, RS and R6 are branched or unbranched alkyl or alkoxy having from 1 to 5 carbons, preferably methyl or 2-butyl, R~ is a branched or unbranched alkyl having from 1 to 4 carbons and m and n can be integers from 0 to 3, where n+m ~ 3, and aluminum triarylo~s:ylates. Particular preference is given to liquid aluminum compounds, in particular aluminum compounds in which R5 is a methyl, R6 is a butyl and the sum of n+m = 3 and the ratio n/m > 0.3.
The first-mentioned catalysts are therefore lower aluminum trialkoxides, such as aluminum trimethoxide, aluminum triethoxide, aluminum triisopropoxide, aluminum tri-sec-butoxide, and compounds which are formed in the reaction of said aluminum trialkoxides with stoichiometric amounts of acetylacetonate, alkyl acetoacetate or alkyl malonate with elimination of alcohol and transesterification. Examples are aluminum triacetoacetate, aluminum triacetylacetonate, aluminum monoacetoacetate diethoxide, aluminum monoacetoacetate diisopropoxide, aluminum diacetoacetate monoisopropoxide.
Preferably, use is made of the aluminum t:rialkoxides, in particular aluminum triisopropoxide and aluminum tri-sec-butoxide. Very particularly preferably, use is made of mixed aluminum triacetoacetates which are: produced by reacting aluminum sec-butoxide or aluminum triisopropoxide with methyl acetoacetate with elimination of 2-butane>1 or isopropanol and + v crif.~..v .~...~. .~.f t ~ cthnxv Qr n " ~ c,. i th the -hpta_npl_ ,.rans~st~y at r. h.. m.. . 1 ~re..p : r_,... 2 isopropanol released, where the degree of transesterification is to be above 30%.
For the purposes of the invention, aluminum triaryloxylates are the aluminum salts of aromatic hydroxy compounds, such as aluminum triphenolate, aluminum tricresol.ates, aluminum trixylenolates, aluminum trinaphtholates, whose aryl radicals can also be substituted by lower alkyl or alk.yloxy groups, i.e. alkyl or alkyloxy groups having from 1 to 4 carbons, hydroxyl groups or 0050/49363 ~ 02343521 2001-03-05 phenyl. Particularly advantageously, of these, use is made of the relatively readily accessible aluminum triphenolate.
It is advantageous to use liquid catalysts or solutions of solid catalysts and to feed these into the reaction vessel in liquid form.~Thus, for example, use can be made of aluminum trialkoxides dissolved in alkyl acetoacetate or in a :mixture of alkyl acetoacetate and an alcohol of the formula II.
The amount of the aluminum compound is generally such that its concentration in the reaction mixture does not fall below 0.050 by weight of Al and, at the start of the reaction, does not exceed 6% by weight of A1. Based on alkyl acetoacetate to be reacted, generally from 0.5 to 5 mold of the aluminum compound are required. For the aluminum triisopro:poxide preferably used and the above-described mixed aluminum triacetoacetate prepared from aluminum sec-butoxide and methyl acetoacetate, amounts of from about 1 to 3 mold, based on the alkyl acetoacetate to be reacted, are used, for example.
When use is made of allyl alcohols of the formula II having a boiling point below 120~C, such as 2-methyl-3-buten-2-ol, it is particularly advantageous if the Carroll reaction is carried out in a cyclic carbonate of the formula VI ~or a y-lactone of the formula VII
R1 \ Rz \ / R1 /"C O, C H C
R \2 C=O C=O
R3\ ~ R3 \
~vz? ~vII~.
where the radicals R1, R2 and R3 are H, methyl or ethyl, preferably H or methyl, and R4 is H, methyl, ethyl, isopropyl, phenyl or methoxymethyl, preferably H or methyl, as solvent.
Suitable cyclic 5-member-ring carbonates of the formula VI are, in addition to the customary alkylene carbonates, such as ethylene carbonate, 1,2-propylene carbonate, isabutylene carbonate and 1,2-butylene carbonate, i.~e. carbonates of the formula VI where R1 to R4 are H or methyl., or R1 to R3 are H or methyl and R4 is ethyl, also those where R1 to R3 can additionally be ethyl and R4 is H, methyl, ethyl, isopropyl, phenyl or methoxymethyl.
The cyclic carbonates used can also be prepared extremely inexpensively industrially by reacting t:he corresponding alkylene oxides with COZ. They generally have boi:Ling points which are so high that, at atmospheric pressure, temperatures of 170~C can be reached without problems.
Particularly suitable 5-member-ring lactones of the formula VII
are y-butyrolactone and 3-methyl-y-butyrolactone, in particular y-butyrolactone.
The y-butyrolactones used according to the invention of the formula VII can also be prepared with ad~Tantage industrially by dehydrogenating the corresponding butanediols.
The alkanol formed in the reaction attaclts the cyclic carbonates or lactones, under the reaction conditions, surprisingly so little that, for example, when use is made of propylene carbonate, the solvent can be reused for up to 10 reaction cycles without any clean-up (cf. comparative example lb). The cyclic carbonate or lactone which is separated off after isolation of the y,8-unsaturated ketone can be fed into new reaction cycles without supplementing the catalyst. Residues of unreacted acetoacetate remain in the solvent and are not lost.
The 5-member-ring carbonates and 5-member-ring lactones are generally used in amounts of from 50 to :10000 by weight, preferably from 100 to 500% by weight, based on y,8-unsaturated ketone formed.
When use is made of alcohols of the formula II which have a boiling point above 140~C, the Carroll reaction can also advantageously be carried out without adding significant amounts of a solvent. This is accompanied by advantages in the workup of the reaction mixture.
The process according to the invention can be carried out batchwise and continuously. When it is carried out continuously, advantageously, the starting compounds and the catalyst are pumped into a reaction vessel which is provided with a heating bath and has an attached condensation apparatus for the alcohol which is eliminated and for discharging t:he carbon dioxide formed and the reaction product is obtained using an overflow.
Using the process according to the invention, the sought-after y,8-unsaturated ketones of the formula I can be obtained in a simple manner in surprisingly high yielda. The tertiary alcohols 0050/49363 ~ 02343521 2001-03-05 eliminated from the acetoacetic ester ca;n be recovered virtually completely.
Examples Example la Carroll reaction of 2-methyl-3-buten-2-o:1 with tert-butyl acetoacetate in propylene carbonate at 180°C
A mixture of 25.7 g of a 92~ pure 2-methyl-3-buten-2-of and 39.8 g of tert-butyl acetoacetate were [aic] added dropwise in the course of 2 hours at 170°C to a mixture of 50 ml (45 g) of 1,2-propylene carbonate and 2.8 g of a separately prepared (in accordance with GB 886 353) aluminum trimethylacetoacetate catalyst. During the dropwise addition, -there was vigorous evolution of C02 and low-boilers which were continuously distilled off (b. p. - 80-85°C). After completion of the dropwise addition, the mixture was stirred for a further 10 minutes until the completion of gas evolution and was then cooled. Then, at approximately 100 mbar, first runnings o:f 2.5 g were distilled and 30.9 g of a main fraction consisting of 96-98~ pure 2-methyl-2-hepten-6-one. The yield (together with the amount remaining in the distillation bottom phase) was 92% of theory.
Example lb (Comparative example) Reaction of 2-methyl-3-buten-2-of with methyl acetoacetate in 1,2-propylene carbonate a) A mixture of 29.03 g (0.25 mol) of methyl acetoacetate (AME;
purity 98%) and 23.68 g (0.275 mol) of 2-methyl-3-buten-2-of (MBE; purity 94%) was pumped at 180°C, with stirring, in the course of 2 hours into a mixture of 45 g of 1,2-propylene carbonate and 2.8 g of a separately prepared (according to GB
886 353) aluminum trimethylacetoacetate catalyst. During this time, C02 escaped and 8 g of low-boilers were distilled off, which low-boilers consisted of about 2/3 of methanol and about 1/3 of unreacted 2-methyl-3-buten-2-ol. The mixture was then stirred for a further 30 minutes at 180°C, and then cooled and, at a reduced pressure of 100 mbar, the desired 2-methyl-2-hepten-6-one was distilled off from the reaction mixture.
b) The distillation residue produced in this case was again admixed with the abovementioned amounts of AME and MBE at 180°C in the course of 2 h, the reaction mixture was stirred for 30 min at 180~C, then cooled and the resultant 2-methyl-2-hepten-6-one was distilled off therefrom.
c) Procedure b) was repeated a further 8 times. The mean yield of 2-methyl-2-hepten-6-one over all i0 batches was 88~ of theory, based on MBE reacted (gas-chromatographic determination using an internal standard).
Example 2a Carroll reaction of 3,7-dimethyl-1,6-octadien-3-of (linalovl) with tert-butyl acetoacetate to form 6,IO-dimethyl-5,9-undecadien-2-one 5.6 g of aluminum trimethylacetoacetate (prepared from aluminum triisopropoxide similarly to GB 886353) were charged, heated to 180~C and at this temperature in the course of 2 h a homogeneous mixture of 115.7 g of linalool and 128 g of tert-butyl acetoacetate was pumped into the reaction vessel. In the course of this there was spontaneous formation of C02 and tert-butanol, which was condensed. 51 g of tert-butanol. were isolated.
After completion of the feed, the mixture was stirred for a further 20 min at an internal temperatures of 180-190~C and was then cooled. The reaction discharge was distilled at a pressure reduced to 0.1 mbar. This produced, in two fractions, a total of 139.7 g of 6,10-dimethyl-5,9-undecadien-2-one (geranylacetone), which is equivalent to a yield of 96g of theory.
Example 2b (Comparative example) Carroll reaction of linalool with methyl acetoacetate As in Example 2a), 5.6 g of the aluminum catalyst described there were charged and a mixture of 115.4 g of linalool and 94 g of methyl acetoacetate was pumped in at an internal temperature of 180~C. In the course of this there was spontaneous formation of C02 and methanol, which was condensed. The reaction solution was, as in Example 2a), stirred for a further 20 min until cessation of the COZ evolution and was then cooled. Distillation was performed under reduced pressure, producing 133 g of geranylacetone. The yield was 91.5% of theory. As byproducts, 1.6 g of 6,10-dimethyl-5,9-undecadien-2-of were formed, which were not detectable in Example 2a). .
0050/49363 ~ 02343521 2001-03-05 Example 3a Carroll reaction of 3,7,11,15-tetramethy:l-i,6,10,14(E,E)hexadecatetraen-3-of (E,E-geranyllinalool) with 5 tert-butyl acetoacetate to form 6,10,14,:L8-tetramethyl-5,9,13,17-nonadecatetraen-2-one (geranylgeranylacei=one) 2.5 g of aluminum tri-tert-butylacetoacei~ate were dissolved at 40~C in 42.1 g of tert-butyl acetoacetate: and 72.5 g of 10 E,E-geranyllinalool were added to this ai= 20°C. This resulting mixture was pumped uniformly into a horizontal heated reaction vessel equipped with an overflow and attached distillation bridge. The feed rate was set so that the' mean residence time was 10 min. The internal temperature was 190-200°C. During the reaction, 15 g of tert-butanol distilled off.
After completion of the feed, the reaction discharge was distilled. This produced 75.9 g of geranylgeranylacetone of a purity of 98.8x. This is equivalent to a yield of 92°s of theory.
Example 3b (Comparative example) Carroll reaction of E,E-geranyllinalool with methyl acetoacetate to form geranylgeranylacetone 2.2 g of aluminum trimethylacetoacetate were dissolved at 60°C in 37.6 g of methyl acetoacetate and the so:Lution was mixed with 87 g of E,E-geranyllinalool. This solution was pumped uniformly into the horizontal reactor vessel described in Example 3a). The pumping rate was matched to the available reaction volume to give a mean residence time of 10 ~ 0.5 min. At an internal temperature of 190-200°C, the mixture reacted continously to form geranylgeranylacetone. After completion of the feed, the contents of the reactor were heated for a further 10 min and then passed to the cooled reaction discharge. Distil:Lation was performed at 0.3 mbar, producing in the main fraction 84.2 g of geranylgeranylacetone of a purity of 97.:10. This is equivalent to a yield of 85% of theory.
Example 4a Carroll reaction of nerolidol with 2-met:nylbut-2-yl acetoacetate 5.6 g of aluminum trimethylacetoacetate were charged into the same reaction vessel as described in Example 4a and heated to 190°C. A mixture of 166 g of nerolidol and 139 g of an isopentyl acetoacetate (purity > 980) prepared in .a manner known per se from isopentanol and diketene was added <iropwise uniformly in the course of 2 h. The reaction temperature was kept by heating at 190-200~C in the course of this. After completion of the feed, the mixture was stirred for a further 15 min and then cooled. This produced 212 g of crude material which was distilled at 0.1 mbar.
Two fractions gave 178.7 g of farnesylaceatone. This is equivalent to a yield of 910 of theory.
Example 4b (Comparative example) Reaction of nerolidol with methyl acetoac:etate:
5.6 g of aluminum trimethylacetoacetate were charged into a 500 ml reaction vessel equipped with a metering device, paddle agitator and a 10 cm column having attached reflux condenser and distillation bridge. The contents were hs~ated to 180-190~C. In the course of 2 h, a homogeneous mixture of 7166.5 g (0.75 mol) of nerolidol and 94 g (0.81 mol) of methyl acetoacetate was pumped in uniformly. The reaction temperature was kept to 180-190~C by external heating. The methanol formed was condensed. After completion of the feed, the mixture was stirred for a further 15 min and then cooled. This produced 20F3 g of crude material which was distilled under greatly reduced pressure. In two fractions, together, 167 g of farnesylace~tone were isolated. This is equivalent to a yield of 85% of theory.
Example 5 Carroll reaction of neralidol with 2-methyl-2-pentyl acetoacetate (isohexyl acetoacetate):
2.8 g of aluminum trimethylacetoacetate were charged into the reaction vessel described in Example 4a. At a reaction temperature of 190-200~C, in the course of 1 h, a mixture of 83 g of nerolidol and 75 g of an isohexyl acet:oacetate (purity > 984) prepared from isohexanol and diketene were pumped in. After completion of the feed, the reaction mixture was stirred for a further 10 min at 200~C and cooled after gas evolution was complete. This produced 108 g of crude material which were distilled under greatly reduced pressure.. 88 g of pure farnesylacetone were isolated in this manner. This is equivalent to a yield of 90% of theory.
Example 6 a) Inventive reaction of E,E-geranyllinalool with tert-butyl acetoacetate 263 ml of a reaction solution consisting of 145 g (0.5 mol) of E,E-geranyllinalool, 5 g of aluminum tri-tert-butyl acetoacetate and 83 g (0.525 mol) of tert-butyl acetoacetate were pumped at a rate of 5.6 ml/min into a magnetically stirred reaction vessel consisting of a 100 ml three-necked flask heated to 190 to 200°C by a heating mantle with an overflow in the center (corresponding to a usable volume of the flask of 45 ml).
This produced 185 g of crude product and 30.5 g of low boilers. The crude product comprised 13% unreacted E,E-geranyllinalool and 79% of the desired geranylgeranylacetone.
b) Reaction of E,E,-geranyllinalool [sick with methyl acetoacetate (Comparative example) 234 ml of a reaction solution consisting of 145 g (0.5 mol) of E,E-geranyllinalool, 5 g of aluminum tri-tert-butyl acetoacetate and 61 g (0.525 mol) of methyl acetoacetate were pumped at a rate of 5.0 ml/min into the abovementioned reaction vessel which was heated to 190 to 200°C.
This produced 199.9 g of crude product and 5.7 g of low boilers. The crude product comprised 53% unreacted E,E-geranyllinalool and only 34% of the desired geranylgeranylacetone.
Comparison of Example 6a with Comparative Example 6b clearly shows that the reaction with the tert-butyl acetoacetate proceeds considerably more rapidly (3 to 10 times more rapidly) than the methyl acetoacetate which has previously been customary for Carroll reactions.
Claims (7)
1. A process for preparing .gamma.,.delta.-unsaturated ketones of the formula by reacting an allyl alcohol or a propargyl alcohol of the formula II
where R1 is H or a saturated or unsaturated branched, unsubstituted or methoxy-substituted hydrocarbon radical having from 1 to 33 carbons and the dotted line can be a further bond between the carbons bearing it, with an alkyl acetoacetate at temperatures of from 150 to 220°C in the presence of an aluminum catalyst and with the alkanol which forms being distilled off, which comprises making use of, as alkyl acetoacetate, an acetoacetic ester of the formula III
where R2 is an alkyl having from 1 to 4 carbons.
where R1 is H or a saturated or unsaturated branched, unsubstituted or methoxy-substituted hydrocarbon radical having from 1 to 33 carbons and the dotted line can be a further bond between the carbons bearing it, with an alkyl acetoacetate at temperatures of from 150 to 220°C in the presence of an aluminum catalyst and with the alkanol which forms being distilled off, which comprises making use of, as alkyl acetoacetate, an acetoacetic ester of the formula III
where R2 is an alkyl having from 1 to 4 carbons.
2. A process as claimed in claim 1, wherein the Carroll reaction is used with an acetoacetic ester of the formula III, where R2 is a methyl.
3. A process as claimed in claim 1, wherein, as allyl alcohol of the formula II, use is made of an alcohol of the type where R1 is a group of the formula IV
where n is an integer from 1 to 5 and x and y are either both H or x is methoxy and y is H, or x and y together are an additional bond between the carbons bearing x and y.
where n is an integer from 1 to 5 and x and y are either both H or x is methoxy and y is H, or x and y together are an additional bond between the carbons bearing x and y.
4. A process as claimed in claim 1, wherein, as allyl alcohol of the formula II, use is made of 2-methyl-3-butene-2-ol, linalool, 6,7-dihydrolinalool, nerolidol, 10,11-dihydronerolidol or geranyllinalool.
5. A process as claimed in claim 3, wherein, when use is made of 2-methyl-3-butene-2-ol as allyl alcohol of the formula II, the reaction is carried out in a cyclic carbonate of the formula VI or a .gamma.-lactone of the formula VII
where the radicals R3, R4 and R5 are H, methyl or ethyl and R6 is H, methyl, ethyl, isopropyl, phenyl or methoxymethyl, as solvent.
where the radicals R3, R4 and R5 are H, methyl or ethyl and R6 is H, methyl, ethyl, isopropyl, phenyl or methoxymethyl, as solvent.
6. A process as claimed in claim 4, wherein, when use is made of 2-methyl-3-butene-2-ol as allyl alcohol of the formula II, the reaction is carried out in a cyclic carbonate of the formula VI or a .gamma.-lactone of the formula VII
where the radicals R3, R4, R5 and R6 are H or methyl.
where the radicals R3, R4, R5 and R6 are H or methyl.
7. A process as claimed in claim 1, wherein, when use is made of alcohols of the formula II having a boiling point higher than 140°C, the reaction is carried out without the addition of significant amounts of a solvent.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19840746.7 | 1998-09-07 | ||
| DE19840746A DE19840746A1 (en) | 1998-09-07 | 1998-09-07 | Process for the production of gamma, delta-unsaturated ketones by Carroll reaction |
| PCT/EP1999/006447 WO2000014046A1 (en) | 1998-09-07 | 1999-09-02 | METHOD FOR PRODUCING η,δ-UNSATURATED KETONES BY CARROLL-REACTION |
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| CA002343521A Abandoned CA2343521A1 (en) | 1998-09-07 | 1999-09-02 | Method for producing .gamma.,.delta.-unsaturated ketones by carroll-reaction |
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| EP (1) | EP1112245A1 (en) |
| JP (1) | JP2002524435A (en) |
| KR (1) | KR20010074970A (en) |
| CN (1) | CN1348434A (en) |
| AU (1) | AU5858399A (en) |
| CA (1) | CA2343521A1 (en) |
| DE (1) | DE19840746A1 (en) |
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| JP2002121166A (en) * | 2000-10-16 | 2002-04-23 | Kuraray Co Ltd | Method for producing unsaturated ketone |
| JP2002121165A (en) * | 2000-10-16 | 2002-04-23 | Kuraray Co Ltd | Method for producing unsaturated ketone |
| WO2008047690A1 (en) * | 2006-10-11 | 2008-04-24 | Eisai R & D Management Co., Ltd. | Process for preparing geranylgeranylacetone |
| CN102050714B (en) * | 2010-12-08 | 2014-02-05 | 重庆恒韵医药有限公司 | Method for synthesizing Teprenone |
| CN103058839B (en) * | 2013-01-25 | 2014-12-17 | 四川源基制药有限公司 | Process for synthesizing and purifying teprenone |
| CN104513117B (en) * | 2013-10-08 | 2016-08-10 | 中国科学院大连化学物理研究所 | A kind of catalysis method of asymmetric synthesis of chiral beta-acetenyl ketonic compound |
| CN104326890B (en) * | 2014-11-21 | 2016-08-24 | 山东新和成药业有限公司 | A kind of Carroll reacts continuous process method |
| CN106946673A (en) | 2015-12-11 | 2017-07-14 | 帝斯曼知识产权资产管理有限公司 | The method for manufacturing the ketone of 6,10,14 trimethylpentadecane 2 |
| WO2018108606A1 (en) | 2016-12-12 | 2018-06-21 | Dsm Ip Assets B.V. | Process for the manufacture of 6,10-dimethylundecan-2-one, isophytol, alpha-tocopherol (acetate) and further intermediates thereof |
| CN116212943A (en) * | 2022-12-05 | 2023-06-06 | 江苏宏邦化工科技有限公司 | Preparation method of novel alkaline catalyst and application of novel alkaline catalyst in preparation of methyl heptenone |
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| DE2928944A1 (en) * | 1979-07-18 | 1981-02-12 | Basf Ag | IMPROVED METHOD FOR PRODUCING HIGHER UNSATURATED KETONES |
| DE19647117A1 (en) * | 1996-11-14 | 1998-05-28 | Basf Ag | Process for the production of gamma, delta-unsaturated ketones by Caroll reaction in cyclic carbonates or gamma-lactones as solvents |
| US6051741A (en) * | 1997-10-17 | 2000-04-18 | Basf Aktiengesellschaft | Preparation of γ,δ-unsaturated ketones by the Carroll reaction, novel catalysts therefor and the preparation thereof |
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| ID27392A (en) | 2001-04-05 |
| EP1112245A1 (en) | 2001-07-04 |
| WO2000014046A1 (en) | 2000-03-16 |
| AU5858399A (en) | 2000-03-27 |
| JP2002524435A (en) | 2002-08-06 |
| KR20010074970A (en) | 2001-08-09 |
| CN1348434A (en) | 2002-05-08 |
| IL141689A0 (en) | 2002-03-10 |
| DE19840746A1 (en) | 2000-03-09 |
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