JPS5849378A - 2,2-disubstituted-5-unsubstituted- or 2,2-disubstituted-5- alkyl-substituted-2,5-dihydrothiophene and its preparation - Google Patents

Abstract

NEW MATERIAL:A compound of formulaI(R1 is alkyl, cyclohexyl which may be substituted by halogen or OH; R2 is H or alkyl; R3 is alkyl or benzyl which may be substituted by alkyl). EXAMPLE:2-Acetyl-2-benzyl-2,5-dihydrothiophene. USE:Useful as a synthetic intermediate for carotenoids, prostaglandins, etc., capable of exhibiting the individual physiological activity, and having the usefulness expected as germicides and insecticides. PROCESS:A 2-substituted carbonyl(-5-alkyl-substituted)-thiophene of formula II is reduced in the presence of liquid ammonia and metallic sodium in an organic solvent, and the resultant product is then treated with an ammonium halide and reacted with a compound of the formula R3X to afford the compound of formulaI.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides O! ! ! ! For example, 6. ? It is useful as a synthetic intermediate such as -octadien-4-one or 9.11-)lysocacyen-8-one.

In addition, 2,2-di-tk-5-unbenzene, which has not been previously described in any literature, exhibits the chemical 1!1 property by itself and is expected to be useful as a bactericidal and insecticide in the fields of medicine, agriculture, and horticulture. The present invention relates to substituted mono- or 2,2-disubstituted-5-alkylated Th-2*5-dihydrotetrathiophores and a method for producing the same.

For further evaluation, the present invention provides the following formula (1), in which R
1 is an alkyl group, preferably C3-C13 alkyl A/Ms
Even if halogens are exchanged.

R3 represents a group selected from the group consisting of a cyclohexyl group and a hydroxyl group, and R3 represents a group selected from the group consisting of a hydrogen atom and a lower alkyl group, preferably a Cr-centered 4-furkyl group, and ``1'' represents a saturated 2,2-dimethyl group represented by ``Mog'' represents an unsaturated lower alkyl group, preferably 61-□, an alkyl group, and a group selected from a benzyl group optionally substituted with a lower alkyl group. Convert to - 5 - Not convert to 1 - or 2.2
-disubstituted-5-alkyldirectly-2,6-dihydrothio7
Concerning enes and their production methods.

The present inventors have been conducting research on the Birch (B(deC) reduction of 2-substituted carbonyl-thiophenes, and this time, we have investigated the reduction of 2-substituted carbonyl-thiophenes, which has not been previously described in the literature. 2-di-substituted-2-di-substituted or 2,2-di-substituted-5
It has been discovered that -alkyl-substituted-2,s-dihydrotetrathiophyls can exist and can be synthesized by easy means. Furthermore, it has been found that the compound of formula (1) is a useful compound as the synthetic intermediate and as a physiologically active compound.

Therefore, one object of the present invention is to provide a compound of the above formula (1), and another object of the present invention is to provide a method for producing the compound of the above formula (1).

The above and many other objects and advantages of the present invention will become more apparent from the following description.

Examples of the alkyl group in R1 of the compound of formula (1) are methyl, ethyl, propyl (%-1 (-○), butyl (%fist, -rho, roa-, t-de-x) Preferred examples include C(-, Cu alkyl groups such as heptyl, octyl, and nonyl. Examples of Schiff-tetrahexyl groups and hydroxyl groups which may be substituted with halogens include halogen-substituted groups such as seven-no or di-substituted with chloro, Examples of lower alkyl groups in R8 include methyl, ethyl, propyl, and butyl. Examples of saturated or unsaturated lower alkyl groups in R1 include methyl and ethyl. , fwat
ru, butyl, allyl, futhynyl (t,!!-18-)
For example, Examples of the benzyl group which may be substituted with a lower alkyl group include a hydrogen atom or a lower alkyl group (e.g., C, -C, alkyl group) or an unsubstituted benzyl group.

The compound of formula (1) can be produced, for example, as shown in the following formula.

(厘) (■
) In the above formula, R1, R1 and R1 are the formula (ri and the formula (
1) Same meaning as already defined and exemplified for K.

In addition, the 5-substituted or unsubstituted thiophine of formula (1) and the compound of formula (1) are known compounds, but in the formula (seal), 6
-Substituted thiophene y can be obtained, for example, by heating and refluxing 3-acyl-thiophene in a zinc amalgam under a constant salt atmosphere according to the following formula.

The 2-acylthiophene represented by the above formula (厘) is, for example, ij%J, R0Jok*ao*, G, E, Ma
y.

Org, 5ysth, Ce1l, VJ-JLe
It can be synthesized according to the method of l(ts's).

For example, anhydrous benzene! Thiophene Kametomichiru and acetyl chloride O0 in OO-! After cooling to 0° C. and gradually adding 2 moles of stannic chloride, stirring at room temperature for 1 hour, adding 100% s”% hydrochloric acid, and extracting with benzene.
The fractions were dehydrated with anhydrous calcium chloride and transferred under reduced pressure.

3-acetylthiophene (ts point is 97~b1gewHg
) can be obtained in good yield.

According to the method of the present invention, for example, the following formula (rin) can be formed as described above, where R1 and R1 are 9 and 1 as stated in formula (1).
It is a town right.

2-directly substituted carbonyl-S-unsubstituted- or 2
The -substituted-5-alkyl-substituted-thio-7-ether compound is subjected to a reduction reaction (Birch reduction) in the presence of chain ammonia and metallic sodium in an organic solvent, and the product is treated with ammonium halide. The target compound of formula (1) can be obtained by reacting with a benzyl halide optionally substituted with an alkyl halide or a lower alkyl group.

Examples of the above-mentioned solvent include lower alcohols such as methanol, ethanol, zolopanol, butanol, etc., ethers such as ethyl ether, tetrahydrofuran, etc., and appropriate mixtures thereof. It is best to use it in

Reduction reaction, tI of the above example! The amount of liquid ammonia used in the reaction, which is carried out under refluxing conditions of liquid ammonia in a bath medium at, for example, about -30°C to about -3I°C, can be selected as appropriate. From about Zoo to about 150 gso molecules based on the compound, more preferably about 150
Examples of lids used include ~200 times the molar ratio. In addition, the amount of metal sodium to be used can be selected as appropriate; for example, the formula (1
) Based on the compound, the amount to be used may be about 2 to about 3 times the mole, more preferably about z2 to about z4 times the mole.

In the reduction reaction, the alkylation or benzylation reaction can be carried out continuously without taking out the reaction product. In the reaction, the product is treated with an ammonium halide, such as ammonium chloride, and then treated with an alkyl halide or a lower Benzyl halides optionally substituted with alkyl groups, e.g.

The reaction that can be carried out by reacting with alkyl bromide or benzyl bromide is performed by adding ammonium halide to the product system and stirring, and then adding alkyl halide or benzyl halide as exemplified above to form a liquid. This can be carried out under ammonia reflux conditions. The amount of ammonium halide to be used can be selected as appropriate, for example, about 1 to about 2 times (more preferably about 1.1 to about 1.3 times) molar amount based on the compound of formula (1). Can give examples of values.

In addition, the amount of a) alkyl y'nide or benzyl halide used is about 2s based on the compound of formula (Otori).
An example of the amount used is about S to about S times the mole, preferably about 3 to about 15 times the mole.

According to the present invention, the target compound of formula (1) can be obtained from the compound of formula (tense) by the method described above. The obtained compound of formula (1) has the title of the invention filed by the same applicant on the same date @2,2-disubstituted-2-unsubstituted mono or 2.
It is useful as an intermediate for use in 2-direlated-5-alkyl-11-2,5-dihydrothiofe/-1-1-dioxides and their production process, and furthermore, it has physiological properties as such. It is expected to be useful as an active substance in medicines, pickles, etc., and as a killer and insecticide.

Hereinafter, the Sudoku style of the present invention will be explained in detail in detail using examples.

Example 1 Synthesis of acetyl-2-benzyl-2,5-dihydrothiophene To about 1110 m of liquid ammonia was added 2-acetylthiophene zs2Ii (!ON Rimol), ethanol 4-, and ether 3-. Metallic sodium 1.0@m+(
Perform birch reduction by adding strips of 46 ken Limol) in 30-40 min, after stirring for 60 min, add 1.3 Jil of ammonium chloride and stir well for se 0th benzyl bromide &01 lj( Add 61? (remol) and make 60
The reaction can be completed by stirring for a minute. All the above reactions are carried out under liquid ammonia reflux temperature (-30 to -35°C).

After the reaction is completed, ammonia is evaporated, treated with hydrochloric acid for 10 seconds, extracted with ether, and neutralized with sodium bicarbonate. After dehydrating the ether bath with anhydrous sodium sulfate, the 2-acetyl-2-benzyl-g
, s-dihydrothio7ey was isolated. The yield is 73
%.

Substance C) IR%MS, HMA and original table analysis values are shown in Table I
K showed.

Example 2 Synthesis of 2-butyryl-2-benzyl-5-butyl-2゜5-dihydrothiophene 1 2-butyrylthiophene (b, 1.111-11 g'C
/11mmRg)2&1. After boiling P (α15 mol) and zinc amyl gum (metallic zinc 1001i, mercuric chloride Log, 1lIi, washed with water) for 10 hours in 10% of water and 100% of hydrochloric acid, After extraction with benzene and washing with water, drying with anhydrous sodium sulfate. The bath medium is removed and distilled under reduced pressure.

&, p, 73-80°C 720ml 11g of 5-butylthiophene is obtained. This 5-butylthiophene is J,
E, Johsaa*, G, A, May,
Org, 5yntk,.

C.11. According to the synthesis method of 2-acetylthiophene of V*L-2g 8 (194B), 2-butyryl-5
-Butylthiophene (Lp, 113~b/4■Htt)
#friend.

Dew-butyryl-5-butylthiophene tgoy (10(
11-
Butyryl-2-benzyl-5-butyl-S-dihydrothiophene is obtained with a good yield of 76%. The analytical values are shown in @l.

懺1K also shows the results of synthesizing the compound of the formula (1) of the formula (1) in the same manner using other metal compounds of the formula (1) of the formula.

Claims (1)

[Scope of Claims] L represents a group selected from the group consisting of the following formula (1), where R1 represents an alkyl group, a cyclohexyl group that may be substituted with halogen, and a hydroxyl group, and R1 represents hydrogen. atoms and lower alkyl groups), and R@Id represents a group selected from the group consisting of a saturated or unsaturated lower alkyl group and a benzyl group optionally substituted on lower alkyl. Indicates a group. 2,2-di-di-replaced-5-unsubstituted one or! ,
2-Disubstituted-5-alkyl-directly substituted-2,5-dihydro I thiophenes. l The E represents a group selected from the group consisting of C, Nc, an alkyl group, a cyclohexyl group, and a drinking group.%
Rs tfi represents a group selected from the group consisting of aqueous atoms and C, C, alkyl groups, and Rs is a group selected from the group consisting of saturated or unsaturated C, -, C, alkyl groups, and benzyl groups. The compound according to claim #M, which shows: Disembarkation ceremony (seal). However, in the formula, R1 represents an item selected from the group consisting of an alkyl group, a cyclohexyl group optionally substituted with halogen, and a hydroxyl group, and R represents an item selected from the group consisting of a hydrogen atom and a lower alkyl group. 2-substituted carbonyl 8-5-unconverted mono or 2 represented by
-Substituted carbonyl-5-alkyl-substituted-thiophene is subjected to a reduction reaction in an organic solvent in the coexistence of liquid ammonia and metallic sodium, and the product is treated with ammonium octane, after which the alkyl halide or lower alkyl group is The following formula (1) is characterized in that it is made to react with a benzyl group optionally substituted with hydrogen, provided that in the formula, Rsti alkyl group, a cyclohexyl group optionally substituted with halogen, and a hydroxyl group are selected from the group consisting of R indicates a group selected from the evaluation of a water atom and a lower alkyl group, and 5- indicates a saturated or unsaturated lower alkyl group and a group substituted with a lower alkyl group. The following nine benzyl groups were selected from among the benzyl groups. 2.
! -Production method of di-5-alkyl-substituted-g,s-dihydro thiophenes. Table 1. The manufacturing method according to item 3, wherein the organic solvent is alcohol, ether, or a mixture thereof.