JPS6039060B2 - Method for producing unsaturated ketones - Google Patents

Description

[Detailed description of the invention]

The present invention relates to the general formula [1] (wherein X. and x2 are both hydrogen atoms or one is a hydrogen atom, the other together with Z represents a single bond, and together with represents a single bond, or is a hydroxyl group or a lower alkoxy group, R is a hydrogen atom or a lower alkyl group, and R is a hydrogen atom or a lower alkyl group;
2 is a lower alkyl group, one of X3 and x4 is a hydrogen atom, and the other together with Z represents a single bond). Or Q.8-, 6. relates to a method for producing unsaturated ketones. Q・3-, y・6-unsaturated ketone and Q・8-, 6-unsaturated ketone (hereinafter referred to as unsaturated ketone [1]) represented by general formula [1] are violet type It is a useful substance as an intermediate in the production of iron as a fragrance. According to the present invention, the general formula [D] (wherein X, .
] (have the same meaning as those in ) (hereinafter referred to as propargyl alcohol)

Unsaturated ketone [1] can be produced by heating and isomerizing [0]. The propargyl type alcohol

[0] is the following general formula [
W] (wherein X,, X2, R,, R2 and O are general formulas [
1), halo is a halogen atom) (hereinafter referred to as
This is obtained by reacting a halogen compound [W]) with mesityl oxide and/or imesityl oxide (hereinafter collectively referred to as mesityl oxides) in the presence of an alkali condensate. 8.y-unsaturated ketone (hereinafter referred to as 8.y-unsaturated ketone) represented by the general formula [m] (wherein X, , It is easily produced by ethynylation reaction of y-unsaturated ketone [m]. This ha. In the condensation reaction between the compound [W] and mesityl oxides, the general formula [V] (wherein X,,X2,R,,
Q.8 monounsaturated ketone (hereinafter referred to as Q.8 monounsaturated ketone [V]) represented by R2 and B have the same meanings as in general formula [1]) is co-produced, but Q.B-unsaturated ketone [V] is easily isomerized to B.y-unsaturated ketone [m]. Therefore, it can be obtained as a co-product by the condensation reaction of halogen compound [W] and mesityl oxides. isomerizing at least a part of the Q.8-unsaturated ketone [V] to 8.y-unsaturated ketone [m],
Additional amount of propargyl type alcohol by ethynylation reaction

[0] can be obtained. Also 8・y−
In the ethynylation reaction of unsaturated ketone [m], Q.8-unsaturated ketone [V] may be produced depending on the reaction conditions, but this by-product Q.B-unsaturated ketone [V]
] can also be converted into propargyl-type alcohol [b] by isomerizing it to an 8-y-unsaturated ketone [machi], if desired, and then subjecting it to an ethynylation reaction. Starting propargyl-type alcohol used in the present invention

Preferred examples of [0] include the following compounds. However, the following structural formula is not intended to specify the three-dimensional structure of the compound. 4-isoprobenyl 3,
6,7-trimethyl-1-octyne-3,7-diol 4-isoprobenyl-3,6,7-trimethyl-7-methoxy1-octyne-3-ol 4-isoprobenyl-3,6,7-trimethyl-1-octyne-6-en-3-ol 4-isoprobenyl -3,6,7-trimethyl-1-octyne-7-en-3-ol 4-isoprobenyl-3,6,7-trimethyl-nonyn-6-en-3-ol 4-isof. Robenyl-6-ethyl-3,7-dimethyl-1-octyne-6-en-3-ol Among these propargyl alcohols, the following general formula [oa] (the dotted line in the formula indicates 2 at any of the positions indicated by this) The compound represented by (indicating the presence of a double bond) is an intermediate for the production of irons by isomerizing it by heating at a temperature range of 130 to 200 ° C. according to the method of the present invention. It is particularly important because it is easily converted to pseudodylon. propargyl alcohol

Among [0], compounds that are not included in the above-mentioned general formula [oa] are of course treated in the same manner as above to obtain corresponding chain Q.8-1, y.6-unsaturated ketones and/or Q・8−, 6・
-Produces unsaturated ketones. In the presence of an alkali condensing agent, the production of 3-y-unsaturated ketone [m] by the reaction of a halogen compound [W] and mesityl oxides is generally carried out to produce a substituted ketone by a condensation reaction between an organic halogen compound and a ketone. It can be carried out by known methods such as the following methods. Wind: A method of condensing an organic halogen compound and a ketone in liquid ammonia in the presence of an alkali amide (Japanese Patent Publication No. 40
(See Publication No. 119091 and Publication No. 40122173). {B}: A method in which an organic halogen compound and a ketone are reacted in a non-aqueous system in the presence of an alkaline condensing agent (e.g., sodium hydroxide, potassium hydroxide) and an amine catalyst or a phosphonium catalyst (Tsubaki Kosho No. 40-122251 and Tokkan (See Publication No. 50-96514.) 'C}: A method of reacting an organic halogen compound with a ketone in the presence of an alkaline condensing agent and a catalyst (amine catalyst, quaternary ammonium salt catalyst, or phosphonium salt catalyst) in a house water system (Special Publication No. 50-137713 and (Refer to Special Publication No. 50-196514). In the condensation reaction between a halogen compound [W] and mesityl oxides, 8-y-unsaturated ketone [m]
At the same time, Q.8 monounsaturated ketone [V] is produced, but both can be easily separated by precision distillation if desired. And this Q.8-unsaturated ketone [V
] is heated in the presence of an isomerization catalyst, for example an acidic catalyst, the Q.B-unsaturated ketone [V] is isomerized to the B.y-unsaturated ketone [m]. 6・y-unsaturated ketone [m] is Q
・It has a lower boiling point than 8-unsaturated ketone [V], so by heating and distilling a mixture of the two under the isomerization reaction conditions of Q-8-unsaturated ketone, 8-y-unsaturated ketone [m
) can also be taken out continuously. Starting propargyl-type alcohol used in the present invention

[0]
is the 8-y-unsaturated ketone [m] obtained by the above method
is produced by subjecting it to a ethynylation reaction known per se. Conventionally used ethynylation methods include the following methods. {a}: A method of ethynylation using a Gregnard reagent (ethynylmagnesium halide, which may be generated in situ, is reacted with a ketone in THF or other suitable solvent). 'b': A method in which acetylene is reacted with an alkali metal such as sodium, potassium, calcium, or an alkali metal in liquid ammonia to form acetylide, and this is reacted with a ketone. {c'; reaction of acetylene and ketone in the presence of strong alkali metal compounds such as potassium hydroxide, potassium alkoxide, and sodium amide in a polar solvent (e.g., N,N-dimethylformamide, dimethylsulfoxide, N-methylpyrrolidone, etc.) How to do it. {d-: A method in which acetylene and ketone are reacted in liquid ammonia in the presence of a catalytic amount of a strong alkali metal compound such as sodium hydroxide, potassium hydroxide, sodium alkoxide, or potassium alkoxide. Considering problems such as production cost and post-treatment, the above-mentioned methods (c- and [d}) are particularly preferable as the ethynylation method used in the present invention. In this case, industrially, sodium hydroxide or potassium hydroxide is used in an amount of 0.1-1% by weight, particularly preferably 0.5 to 3% by weight, based on the 3-y-unsaturated ketone [m] used. % and the reaction temperature is preferably in the range of -5 to 5°C. Propargyl type alcohol obtained in this way

In the present invention, [0] undergoes a rearrangement reaction by heating and is induced to unsaturated ketone [V]. This rearrangement reaction can be carried out in either liquid phase or gas phase, and the reaction temperature can be 100 to 400°C, but from the viewpoint of reaction rate, in the case of liquid phase method,
0 to 230 qo is preferable, and in the case of a gas phase method, 250 to 400 qo is preferable, although it depends on the residence time. Although the reaction may be carried out in the atmosphere, it is usually preferable to carry out the reaction under an atmosphere of an inert gas such as nitrogen or helium. There is no particular limitation on the reaction pressure, and the reaction can generally be carried out satisfactorily under atmospheric pressure. However, propargyl alcohol

When the boiling point of [0] is lower than the reaction temperature used, or when a gas phase method is employed, it is preferable to carry out the reaction under increased or reduced pressure that meets these conditions. Although the use of a solvent is not essential, a solvent such as alcohol that is stable under rearrangement reaction conditions and does not participate in the reaction or improves selectivity may be used. The usefulness of the unsaturated ketone [1] produced according to the present invention will be explained using 4-isoproverobenyl 3,6,7-trimethyl contained in the probargyl alcohol [na] which is particularly preferably used as a starting material in the present invention. -1-Octyne-6-Yen-3
-To explain using ol [ob] as an example, 6,9,10-trimethyl-3,5,9 produced by a heated rearrangement reaction of mb] shown by the following formula.
-undecatrien-2-one [la] and 6,9,
10-trimethyl-3,6,9-undecatriene-2
-one [lb] can be converted into silones, which are important as fragrances, by moat using phosphoric acid or sulfuric acid as a catalyst. Next, the present invention will be specifically explained with reference to Examples. Example 1 980 g of mesityl oxide, 590 g of 2,3-dimethyl-1-chloro-2-butene and 25 g of trimethylstearylammonium chloride were added to a solution of 600 g of sodium hydroxide and 490 g of water, followed by water bathing. The reaction was terminated after 2 hours. The reaction solution was poured into water, extracted with ether, washed with water, and dried. After distilling off the solvent under reduced pressure, excess mesityl oxide was recovered and 3-isoprobenyl-5,6-dimethyl-
5-hepten-2-one and 3-isof. Ropylidene-5
, 6-dimethyl-5-hepten-2-one, 730 g of a 6:1 mixture was obtained. The structure of the product was confirmed by the following method. Infrared absorption spectrum (skin-1) 3070, 17
12 (>C=〇), 1640 (>C;C<), 1445
, 1373, 1350, 1152, 898 Nuclear magnetic resonance spectrum (No. 6 blind spot 14) 1.51, 1.54, 1.57, 1.5 $, 12 days, C
H3-1-93 S, milk day, 1.88-2.55m, 2
Sun, 3.13 t. IH. 4.73 s, 2H=C ratio 5 Three flasks of liquid ammonia were put into the three flasks, 70 m of sodium metal was added thereto, and then acetylene gas was blown into the flasks. When the reaction solution turned gray, the injection of acetylene gas was stopped and 3-benyl-5,6-dimethyl-5
- Hepten-2-one (560 g) was added thereto, and then acetylene gas was blown into the mixture to react for 3 hours. After removing ammonia, the mixture was neutralized with ammonium chloride, poured into water, and extracted with ether. After drying with glass powder, the solvent was removed under reduced pressure. Further, the residue was distilled under reduced pressure to a boiling point of 89 to 920 (2.
585 fractions of 30% of the total weight were obtained. This product contains 3-isoprobenyl-5,6-dimethyl-5-hepten-2-one (3.5%), 3-isopropylidene-5,6-dimethyl-5-hepten-2-one (12.5%), 4-isoprobenyl 3, It was a mixture of 6,7-trimethyl-1-octyne-6-en-3-ol (84%). Confirmation of the structure of the product involved the following method. Infrared absorption spectrum (Ka-1) 3440 (1OH) 3300 307
0, 163 ku 14501375 900 Nuclear Magnetic Resonance Spectrum (14 every 6 horses) 1-41S, Chihiro, 1-56S, Indo-Japan, CH3-1.748ach s, Chihito, CH3- ■ 2.21~2. 45m, 2 days per day H-2.31
s, IH, 1C3CH4.86 s, 2 days, =CQ then 4-isoprobenyl-3,6,7-trimethyl-
1-octyne-6-en-3-ol (purity 84
%) was placed in a three-necked flask and heated under a nitrogen atmosphere at an internal temperature of 16 yo for 4 hours to carry out a rearrangement reaction. The reaction solution was vacuum distilled as it was to remove the low boiling point fraction containing the raw materials and reactants, and then the high boiling point fraction (boiling point 103-105
qo/0.7 side), the target object 6,9,10-trimethyl-3,5,9-undecatrien-2-one and 6,9,10-trimethyl-2-one with a composition ratio of 1:1.5
101 grams of 3,6,9-undecatren-2-one (purity 93%) was obtained. These were a mixture of 3 to 7 cis and trans isomers each. Infrared absorption spectrum (skin-1) 1718 1668 1630, 1587, 144 and above
13701360, 125fu 1156, 970, 88
6,9,10-trimethyl-3,5,9-undecatrien-2-one and 6,9 in the 5 mass spectrum
, 10-trimethyl-3,6,9-undecatryen-2-one.
124, 10983, 55, 43 and 41 (100%
) is strong, whereas the main fragment of the latter is m/e43 (100%). Examples 2 to 6 Various alkyl halides [W] and mesityl oxides were condensed under various conditions, and the resulting B.y-unsaturated ketones were subjected to an ethynylation reaction under various conditions to form propargyl. Type alcohol [D]. Next, this product was subjected to a heating rearrangement reaction to obtain the corresponding unsaturated ketone [1]. The results are shown in Table 1. Table 1.

Claims (1)

[Claims] 1 General formula [II] ▲ Numerical formulas, chemical formulas, tables, etc.▼ (In the formula, X_1 and X_2 are both hydrogen atoms, or one is a hydrogen atom and the other is combined with Z_1 represents a single bond, Z_1 together with X_1 or X_2 represents a single bond, or is a hydroxyl group or a lower alkoxy group, R_1 is a hydrogen atom or a lower alkyl group, and R_2 is a lower alkyl group) There are general formulas ▲ mathematical formulas, chemical formulas, tables, etc. ▼ that are characterized by thermal isomerization of propargyl alcohol represented by
have the same meaning as those in formula [II], one of X_3 and X_4 is a hydrogen atom, and the other represents a single bond together with Z_2) α・β−, γ
・δ-unsaturated ketone and/or α・β−, δ・ε−
Method for producing unsaturated ketones. 2 General formula [VI] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, X_1 and X_2 are both hydrogen atoms, or one is a hydrogen atom, and the other together with Z_1 represents a single bond, Z_1 together with X_1 or X_2 represents a single bond, or is a hydroxyl group or a lower alkoxy group.
II]▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, X_1, X_2, and Z_1 are as shown in formula [VI], and one of X_3 and (represents a single bond)
α・β-, γ・δ-unsaturated ketones and/
or the method for producing α/β-, δ/ε-unsaturated ketones according to claim 1. 3 Structural formula [VIII] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ General formula [IX] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula One of X_3 and X_4 is a hydrogen atom,
The other is α, β-, γ, δ-unsaturated ketone and/or α represented by (together with Z_2 represents a single bond)
・Claim 1 of β-, δ/ε-unsaturated ketones
Manufacturing method described in section. 4 General formula [IV] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, X_1 and X_2 are both hydrogen atoms, or one is a hydrogen atom, and the other together with Z_1 represents a single bond, Z_1 together with X_1 or X_2 represents a single bond or is a hydroxyl group or a lower alkoxy group, R_1 is a hydrogen atom or a lower alkyl group, R_2 is a lower alkyl group, ha
The general formula [III] is obtained by reacting a halogen compound represented by (lo is a halogen atom) with mesityl oxide and/or isomesityl oxide in the presence of an alkaline condensing agent [III] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼
(where X_1, X_2, R_1, R_2, and Z_1
have the same meaning as those in formula [IV]) By ethynylation reaction of the β/γ-unsaturated ketone represented by formula [II] ▲ Numerical formula, chemical formula, table, etc. ▼ (in the formula X_2, R_1, R_2 and Z_1
has the same meaning as those in formula [IV]), and the general formula [I] ▲ mathematical formula, chemical formula, which is characterized by heating and isomerizing it.
There are tables, etc. ▼ (In the formula, X_1, X_2, R_1, R_2 and Z_1
have the same meaning as those in formula [IV], one of X_3 and X_4 is a hydrogen atom, and the other represents a single bond together with Z_2) α・β−, γ
・δ-unsaturated ketone and/or α・β−, δ・ε−
Method for producing unsaturated ketones. 5 General formula [X] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, X_1 and X_2 are both hydrogen atoms, or one is a hydrogen atom, and the other together with Z_1 represents a single bond, Z_1 together with X_1 or X_2 represents a single bond, or is a hydroxyl group or a lower alkoxy group, and halo is a halogen atom). Or, the general formula obtained by reacting with isomesityl oxide [XI] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (wherein X_1, X_2 and Z_1 have the same meanings as those in formula [X]) By ethynylating β/γ-unsaturated ketone, the general formula [XII]
▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, X_1, General formula [XIII] ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (In the formula, X_1, Claim 4 of α・β-, γ・δ-unsaturated ketones and/or α・β-, δ・ε-unsaturated ketones represented by (together with Z_2 represents a single bond) Manufacturing method described. 6 Structural formula [XIV] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ Structural formula [XV] obtained by reacting a halogen compound represented by with mesityl oxide and/or isomesityl oxide in the presence of an alkali condensing agent ▲There are mathematical formulas, chemical formulas, tables, etc. ▼ By ethynylation reaction of β-γ-unsaturated ketone represented by , propargyl alcohol represented by the structural formula [VIII] [IX] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, one of X_3 and X_4 is a hydrogen atom, and the other together with Z_2 forms a single bond.) 5. The method for producing α·β-, γ·δ-unsaturated ketones and/or α·β-, δ·ε-unsaturated ketones represented by the following formula.