JPS59172485A - Production of 2,2-dimethyl-1,3-dioxin-4-one derivative - Google Patents

Abstract

PURPOSE:To obtain economically and advantageously the titled compound which is not easily produced, by reacting a beta-keto-acid with acetone in the presence of an acid catalyst and acetic anhydride, etc. CONSTITUTION:A beta-keto-acid of formula I (R1 is alkyl, aryl or aralkyl; R2 is H, alkyl, aryl or aralkyl; R3 is H) is reacted with acetone in the presence of an acid catalyst, e.g. concentrated sulfuric acid, and acetic anhydride or ketene or reacted with isopropenyl acetate of the formula CH2=C(Me)-O-COMe to give the aimed compound of formula II.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides 2,2-dimethyl-1,3-dioquinone-4-
This invention relates to a method for producing on derivatives (general formula (1), in which R, , R2 means hydrogen, alkyl, aryl, or aralkyl group).

However, the intention is to economically advantageously produce the title compound, which is considered to be a synthon of acylketene (R,.CH-GO.C(R2)=C=0), which is difficult to produce.

2,2,6-drimethyl-1,3-dioxin-4-one (II, in the formula R1 means a methyl group and R2 means hydrogen) is known as a so-called diketene-acetone adduct,
It is a compound that is more easily obtained with diketene and acetone (M.F. Carroll, A.R. Ba
der.

J. Amer. Chem. Soc. , 75,
5400 (1953)). Also, its sonoreactivity has been carefully studied, and it has been known for a long time that it exhibits the same reaction as diketene.

A theory of the formation of an acetyl ketene (CH3.Co-CH=C=0) intermediate has been proposed (G, Jager, J
, Wenzelburger, Ann, Chem.
,.

1'976, 2905). Furthermore, the present inventor has confirmed the production of this intermediate (M, 5ato, N, Ka
numa, T, Kato, Chem, Phar
m.

Bull, 30.4359 (1982)).

From the above facts, 5.6-substituted-2,2-dimethyl-
If 1,3-dioxin-4-one (general formula (1)) is obtained, it means that an acylketene has been produced, and simultaneous reaction of dimers of different ketenes (mixed diketenes) is expected.

However, there is a lack of literature regarding the production of such 1,3-dioxinone derivatives, and after acetylation (or propionylation) of Meldrum's acid, 6
-Methyl (or ethyl-2,2-methyl-1,3-
Method for producing dioxin-4-one (Formula: R means methyl or ethyl, R2 means hydrogen) (Iwaki et al. 9th Special 79.106478; Chem, Abst.
92.41966n (1980)), cyclopenta-2,2-dimethyl-1,3-dioxin-4-one using diazoketone (general formula ■2, R+ + R2 is -(
Method for producing CH2) (meaning CH2)3- (G, Jag
er, Ber,, 105°137 (1972)
, and 4-benzoyl-5-phenyl-2,3-disodrofuran-2,3-dione were heated in acetone to give 5
-benzoyl-2,2-dimethyl-6-phenyl-1,
A method for producing 3-dioxin-4-one (general formula 11. R, haphenyl group, R2 means benzoyl group) (G, Kollenz et al.).

Z, Naturforsh, 32. B (6)
, 701 (1977)) is known.

On the other hand, this method uses β-keto acid or its ester, so it is advantageous as a general synthesis method in that R1 and R2 can be freely selected, and it can be said to be an excellent method in terms of operation and yield. .

That is, β-keto acid (in the general formula 12, R1 is an alkyl or aryl group, and R2 is an alkyl, aryl, or aralkyl group).

Add concentrated sulfuric acid to a mixture of (R3 means hydrogen), acetone, and acetic anhydride, stir under water cooling, leave at 5° or less (in a refrigerator) for about 12 hours (2 to 3 hours at room temperature), and neutralize. Then, the desired title compound (in the general formula (1)5, R3 represents an alkyl or aryl group, and R2 represents a hydrogen, alkyl, aryl, or aralkyl group) is obtained. In this case, the appropriate molar ratio of β-keto acid (I), acetone and acetic anhydride is 1°2:2. Also, use an appropriate catalytic amount of concentrated sulfuric acid (
A method).

At this time, the desired compound (2) can also be produced by using ketene instead of acetic anhydride. That is, a small amount of concentrated sulfuric acid is added to a mixture of β-keto acid (general formula ■) and about 4 times the equivalent of acetone,
Pass ketene (approximately 4 equivalents) through the mixture while stirring and cooling with water.

The reaction solution was left in the refrigerator for about 12 hours, and then treated in a conventional manner to obtain the target compound (Method B).

These methods basically involve acetone reacting with acetic anhydride or ketene to form impropenyl acetate (CH2=C
It can be considered that (Me) 0.COMe) is produced and this reacts with the β-keto acid. Therefore, this method also includes a method using commercially available impropenyl acetate. That is, β-keto acid (in the general formula 11, R represents an alkyl or aryl group, R2 represents a hydrogen, alkyl, aryl, or aralkyl group, and R3 represents hydrogen) and about twice the equivalent of isopropenyl acetate. Add a catalytic amount of concentrated sulfuric acid to the mixture, stir for 2 to 3 hours under water cooling, and then leave in the refrigerator for 12 hours. The target product (2) is obtained by post-treatment in a conventional manner (Method C).

Note that some β-keto acids (R3 in General Formula 12 is hydrogen) are easily decarboxylated, and when used as a raw material, it may be advantageous to use an ester. In particular, when the substituent on the ester moiety is easily eliminated, the title compound (2) can be produced by the above procedure. Therefore, the present invention uses free β-keto acids (
β-keto acid ester (R,, R2 in General Formula 19 means hydrogen, alkyl, aryl, or aralkyl group, R3 means alkyl or aralkyl group) instead of (R3 in General Formula 11 is hydrogen) The method used is also considered.

That is, β-keto acid ester (R,, in general formula 11)
R2 means hydrogen, alkyl, aryl, or aralkyl group, R3 means alkyl or aralkyl group), acetone (about 2 times the equivalent), and acetic anhydride (about 3 times the equivalent) under water cooling, and concentrated sulfuric acid was added. After stirring, leave it in the refrigerator. about 12
After a period of time, the title compound (II) is obtained by treatment in the same manner as in the previous method. In this case, it is particularly advantageous for R5 in the ester (I) to be a substituent that is easily eliminated, such as a tertiary phthyl group (method D).

The method of the present invention will be explained below by way of examples.

Example 1 β-keto acid (in general formula 12, R1 is methyl,
Phenyl.

p-methoxyphenyl, p-nitrophenyl group, R2
is hydrogen.

A method of reacting methyl, ethyl, phenyl, benzyl group + R1 means hydrogen) in the presence of acetic anhydride and concentrated sulfuric acid in acetone (Method A) β-keto acid I (0,05 monoly, acetone (5 ,8g,
0.1 mole).

To a mixture of acetic anhydride (10.2 g, 0.1 mol) was added dropwise 0.01 monol of sulfuric acid (Ig) while stirring with water cooling, and 5
Stir for 3 hours below 50°C.

During this time, the reaction solution becomes clear. After leaving it in the refrigerator for 12 hours,
Pour into 10% soda carbonate and stir at room temperature. The precipitated crystals are collected by filtration, washed with water, dried, and then purified by recrystallization. When the target product is liquid, it is extracted with ether, dried, and purified by distillation using a conventional method. The melting point (boiling point), crystal form, and recrystallization solvent are as shown in the table.

Example 2. 2.2-dimethyl-6-phenyl-1,3
-Dioxin-4-one (Ilg; General formula ■9 R3 in formula
represents a phenyl group, R2 represents hydrogen) (Method B) Benzoylacetic acid (R3 represents a phenyl group in the general formula 12,
R2 and R3 mean hydrogen) (1,64g, I
Omi! The ketene (40 mmol) is passed through a mixture of acetone (2.32 g, 40 mmol) and concentrated sulfuric acid (0.4 g, 4 mmol) under water cooling. After stirring for 30 minutes, the mixture was left in the refrigerator for 12 hours, poured into a 10% sodium carbonate solution, and stirred at room temperature to precipitate crystals. When this was collected by filtration, dried and recrystallized with hexane-ether, the mp6
126 g (62%) of 2-63° needles are obtained. Elemental analysis value, calculated value (C, □H,,0,): C,75,5
7; H, 5, 79, actual value C, 70, 47; H, 5,
79, Infrared absorption spectrum (CHCX3) cm'
; 1111.1632, NMR (CDCl2) pp
m: 1.80 (6H, s, methyl), 5.88 (
IH,s, olefin), 7.85 (5H.

S, benzene).

Example 3 β-keto acid (general formula 11.R represents a methyl or aryl group.

Method of treating R2 (hydrogen, methyl, ethyl, phenyl, or benyl group) with impropenyl acetate in the presence of concentrated sulfuric acid (Method C) β-keto acid (n, 0.05 mol) ), impropenil acetate (10 g.

A mixture of 0.01 mol) and concentrated sulfuric acid (Ig, 0.01 mol) was stirred for 3 hours under water cooling. After leaving it in the refrigerator for 12 hours,
Post-treatment is performed in the same manner as in Example 1 to obtain the desired 1,3-dioxinone (n). The yield etc. are as shown in the table.

Example 4. β-keto acid tert-butyl ester (general formula 19
A method of ring-closing (R, , R2 means hydrogen, alkyl, aryl, aralkyl group, R3 means tertiary butyl group) in the presence of acetic anhydride and concentrated sulfuric acid in acetone (Method D) β-keto acid tertiary butyl ester (n, 0.03 mol),
Acetone (3.5 g, 0.03 mol), acetic anhydride (
9 g, 0.09 mol) was added with water-cooled concentrated sulfuric acid (3
g, 0.03 mol) was added dropwise and stirred for 3 hours. Leave in the refrigerator for another 12 hours, then pour in 10% carbonated soda. The desired dioxinone compound (It) is obtained by post-treatment in the same manner as in the previous example. The results are shown in the table.

Note: Two-element analysis values, infrared absorption (CHCI, ) and NMR
The spectrum (CDCb) satisfies structure (2).

Claims (1)

[Claims] 1 β-keto acid (in the following general formula I2, R1 represents an alkyl rule or aralkyl group, R2 represents hydrogen or an alkylralkyl group, and R3 represents hydrogen) is dissolved in a solution such as concentrated sulfuric acid. with acetone in the presence of an acid catalyst (using acetic anhydride or ketene) or impropenyl acetate (CH
2,2-dimethyl-1,3-dioxin- characterized by reacting with 2-C (Me).O-COMe)
4-one derivative (general formula ■, in the formula R1 is alkyl, aryl, aralkyl, alkyl, aryl, aralkyl 2 β-keto acid ester (the following general formula ■, in the formula R,,R
2+ meaning hydrogen, alkyl, aryl, aralkyl aralkyl group) using an acid catalyst such as concentrated sulfuric acid. 2,2-dimethyl-1,3-dioxin-4-one derivatives characterized by reacting with acetone in the presence of acetic anhydride (general formula 1, in which R and R2 are hydrogen, alkyl, aryl, or aralkyl) (meaning group)