JPS62207275A - 2-acyldihydroyrrolopyrrole compound and production thereof - Google Patents

Abstract

NEW MATERIAL:The 2-acyldihydropyrrolopyrrole compound of formula I (R1 is H, lower alkyl or lower alkoxycarbonyl; R2 is H, lower alkyl, aralkyl or aryl; R<3> is H, lower alkyl or trialkylsilyl). EXAMPLE:3,6-Di-t-butyl-2-formyldihydropyrrolo[3,2-b]pyrrole. USE:Useful as an agricultural chemical, pharmaceutical or its intermediate raw material. Useful also as a raw material for electric and electronic material. PREPARATION:The compound of formula I can be produced by acylating the dihydropyrrolopyrrole compound of formula II with an acylation agent. The acylation agent is an electrophilic acylation agent for so-called aromatic compound and used at an amount of usually iota1mol per 1mol of the compound of formula II.

Description

Detailed Description of the Invention <Industrial Application Field> The present invention is based on the general formula (1) (wherein R1 is a hydrogen atom, a lower alkyl group, or a lower alkoxycarbonyl group, and R3 is hydrogen, a lower alkyl group, or an aralkyl group). group or aryl group, R1 is hydrogen,
Represents a lower alkyl or trialkylsilyl group.

) and a method for producing the same.

<Prior Art> Several types of dihydropyrrolopyrroles without a substituent at the 2-position are known. Example 1, (Angew,
Chem, 1nternat, Edit,, 1
4. 847 (1975), Tetrahedron
Lett,, 24. 2275 (1988), Te
trahedron Lett,, 25.5669 (
1984), Chem, Lett, 198 L 1
809 <Problems to be Solved by the Invention> However, no dihydropyrrolopyrroles having a substituent at the 2-position are known.

Means for Solving Problems〉 The present inventors have made repeated efforts to produce dihydropyrrolopyrroles having a substituent at the 2-position, and as a result, they have succeeded in acylating a specific dihydropyrrolopyrrole compound. By acting with the agent, only the 2-position undergoes selective acylation,
The inventors discovered that the corresponding monoacyl compound can be obtained easily and in high yield, and completed the present invention after various studies.

That is, the present invention relates to (1) general formula (1) (wherein R1 is a hydrogen atom, a lower alkyl group or a lower alkoxycarbonyl group, R1 is a hydrogen atom, a lower alkyl group, an aralkyl group or an aryl group, and Rs is hydrogen 2-acyldihydropyrrolopyrroles represented by (2) general formula (1) (wherein R1 and R represent the same meanings as above). (In the formula, R1e R and I R11 represent the same meanings as above.) Provided is a method for producing 2-acyldihydropyrrolopyrroles represented by the following formula.

The target compound of the present invention is 2-
Acyl dihydropyrrolopyrroles are R1, R,,
Examples of the lower alkyl group in R include methyl,
Examples include lower alkyl groups having 1 to 8 carbon atoms such as ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. Examples of the lower alkoxycarbonyl group in R1 include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, t
Examples include lower alkoxycarbonyl groups having 2 to 9 carbon atoms such as -butoxycarbonyl, pentoxycarbonyl, hexoxycarbonyl, heptoxycarbonyl, and octoxycarbonyl.

Examples of the aralkyl group for R8 include benzyl, tolylmethyl, anisylmethyl, chlorophenylmethyl, phenylethyl, and phenylpropyl, and the total number of carbon atoms is usually 7 to 12. Further, examples of the aryl group include phenyl, tolyl, anilyl, chlorophenyl, naphthyl, etc., and the total number of carbon atoms is usually 6 to 11.

Further, examples of the trialkylsilyl group in R3 include trimethylsilyl, triethylsilyl, tripropylsilyl, etc., and the number of carbon atoms contained is usually 8 to 12.

The 2-acyl dihydropyrrolopyrroles represented by the general formula (I), which are the subject of the present invention, can be used as pharmaceuticals, agricultural chemicals, intermediates thereof, or raw materials for electrical and electronic materials, and are The dihydropyrrolopyrroles shown can be produced in high yield by acylating them with an acylating agent.

According to such a method, acylation occurs regioselectively to adjacent carbon atoms of the nitrogen atom, and only monoacyl forms can be selectively obtained.

As the acylating agent, a so-called electrophilic acylating agent for aromatic compounds is used.

For example, 1” Modern 5y by H, O, House.
ntheticReaction, 2nd Ed,
J pp. 797-816, (W, A.

The Holt/Ll agent, known as the Wilameier-Haack method, includes agents such as those described in J.D. Benjamin. Fr1edel-Cr
Acylating agents known as the afts method are particularly effective.

The formylating agent used in the Wilsmeier-Haack method is a reaction product of equimolar amounts of N,N-disubstituted formamide and phosphorus oxychloride, but it is usually an equimolar reaction product for dihydropyrrolopyrroles (1). More than a molar amount is used. As the solvent, halogenated hydrocarbons such as ethylene chloride and methylene chloride are usually used. The reaction temperature in this case is usually from 0°C to the boiling point of the solvent, and the reaction is usually completed in 6 minutes to 24 hours. The di-substituted chloromethyl group at the 2-position produced by the reaction is usually converted to a formyl group by adding sodium acetate or the like and hydrolyzing it.

In addition, the acylating agents used in the Fr1edel-Crafts method include lower alkanecarboxylic acids such as acetic acid, propionic acid, butyric acid, pentanoic acid, hexanoic acid, heptanoic acid, octanoic acid, and nonanoic acid, phenylacetic acid, tolylacetic acid, anisylacetic acid, and chlorophenylacetic acid. , phenylpropionic acid, phenylbutyric acid and other aryl alkane carboxylic acids,
Examples include arene carboxylic acids such as benzoic acid, methylbenzoic acid, methoxybenzoic acid, chlorobenzoic acid, and naphthoic acid, as well as halides and acid anhydrides of these carboxylic acids. Usually, anhydrous aluminum chloride, zinc chloride, cotton tetrachloride,
Lewis acids such as titanium tetrachloride or phosphoric acid, Borilly 4
Usually, equimolar or more is used with protic acids such as chlorobenzene, nitromethane,
Carbon disulfide etc. can be used. Reaction temperature is usually 0
The reaction temperature is selected from a range between .degree. C. and the boiling point of the solvent used, and the reaction is usually completed in 80 minutes to 24 hours. The resulting reaction mixture is usually hydrolyzed in the presence of a mineral acid such as hydrochloric acid or sulfuric acid to derive the desired product.

The acylated product can be isolated and purified by conventional means, such as extraction with organic solvents, distillation, sublimation, recrystallization, or various chromatography methods.

<Effects of the Invention> The compounds of the present invention are useful as, for example, agricultural chemicals, medicines, or intermediate raw materials thereof, and can also be used as raw materials for electrical and electronic materials.

Furthermore, according to the method of the present invention, monoacyl compounds can be obtained selectively and in high yields.

<Examples> Next, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to these in any way.

Example 1 (8,6-di-tert-butyl-2-formyldihydropyrrolo(8,2-b)pyrrole) In 10 s/ml of ethylene chloride, 1768 da (0,248 mmol) of dimethylformamide, 87 ml of phosphorus oxychloride.・8 Wg (0,248t
(0,0
45 molar) was added and the mixture was stirred for 2 minutes at room temperature under a nitrogen atmosphere.

To the obtained solution was added 10 Mt of 40% aqueous sodium acetate solution, and the mixture was heated under reflux for 15 minutes.

After cooling the reaction mixture, the ethylene chloride layer was separated. Extract the aqueous layer with chloroform (10ml x 2 times), mix the ethylene chloride layer and the chloroform layer, wash with water, and dry.
Concentration under reduced pressure gave brown crystals 12.211Iy. The product was isolated and purified using TLC to obtain 8,6-di-t-butyl-2-formyldihydropyrrolo(8,2-b]pyrrole 10.1jIF (yield 90%).

pmr (CDC13) δI) pm: 1.80 (9H,
S), 1.58 (9H, S), 6-78 (I Hld
*J = 8-8 Hz), 7.57 (IH, NH
), 8.65 (LH, NH), 9.90 (IH, S) Mass analysis m/e: 246 (M+) Example 2 (8,6-di-t-butyl-1,4-dimethyl-2- Formyl-dihydropyrrolo[8゜2-b]pyrrole) 17 s of dimethylformamide in 10 s of ethylene chloride
．． 8 W (0,248 mmol), oxychloride: /
87.8'lF (0,248 mmol) and 8.6-
di-t-butyl-1,4-dimethyl-dihydropyrrolo(
so 2-b) Pillow 71710, 0”F (0,0
407 t remol) was added and the mixture was heated under a nitrogen atmosphere for 15
The mixture was heated to reflux for a minute.

A 40% aqueous solution of sodium acetate for 10 hours was added to the resulting solution, and the mixture was further heated under reflux for 16 minutes.

The reaction mixture was separated and the aqueous layer was extracted with chloroform (
10gj x 2 times). The combined organic layers were washed with water, dried, and concentrated under reduced pressure to give brown crystals 12. Olq was obtained. When purified by silica gel column chromatography and eluted with chloroform, yellow crystals of 9.8 # (yield 88%) were obtained.
was gotten.

This crystal was confirmed to be 8,6-di-t-butyl-1°4-dimethyl-2-formyldihydropyrrolo(a,2-b)pyrrole.

pmr(CD(J3)δppm: 1.85 (9H,
S), 1.56 (9H, S), 8.78 (8H, S)
, 4.12 (8H, S), 6.58 (IH, S), 1
0.10 (IH, S).

Mass analysis m/e: 274 (M+) Example 8 (8,6-bis(trimethylsilyl)-1°4-di(methoxycarbonyl)-2-formyl-dihydropyrrolo(
8,2-b) Pyrrole) In 10sZ of ethylene chloride, 80.61FC0,418t mol of dimethylformamide), 46.1 mol of phosphorus oxychloride (0,418 mmol)
and 8,6-bis(trimethylsilyl)-1.

4-di(methoxycarbonyl)-dihydropio(8,
2-b) 25.5 wg (0,0697 i mol) of Piol was added, and the mixture was stirred at room temperature for 8.6 hours under a nitrogen atmosphere.

To the resulting solution was added 10 ml of 40% aqueous sodium acetate solution.
was added and further stirred at 20°C for 48 hours. The reaction mixture was separated and the aqueous layer was extracted with chloroform (20111
/Xi times). The combined organic layers were washed with water, dried, and concentrated under reduced pressure to obtain pale yellow crystals. This was purified by column chromatography to obtain 19.1lf (yield 72%) of 8.
6-bis(trimethylsilyl)-1,4-di(methoxycarbonyl)-2-formyldihydropyrrolo(8,2-
b) Pyrrole crystals were obtained.

pmr (CD(J, ) δ1)I)m: 0.82
(9H,S), 0.40(9H,S), 8.97(8)
(,S),4. QO (8H, S), 7.42 (IH, S
), 10.05 (IH,S) mass analysis m/e:894
(M”) Example 4 (1,4-di(methoxycarbonyl)-2-formyldihydropyrrolo(8,2-b)pyrrole) Dimethylformamide 2 in ethylene chloride (10sZ)
54 μl (8.28 mmol) and 802 μl (8.28 t mmol) of phosphorous oxychloride were dissolved and the mixture was stirred at room temperature for 15 minutes under nitrogen atmosphere.

The obtained solution was converted into 1,4-di(methoxycarbonyl)-
1,4-dihydropyrrolo[8°2-b]pyrrole 120
W (0,541 mmol) in ethylene chloride solution (20 t
tl) over 30 minutes, and the mixture was further stirred at room temperature for 1 hour.

Add to this an aqueous solution of 15g of sodium acetate (801111)
After addition, the mixture was heated to reflux for 1 hour.

After cooling, the organic layer was separated, and the aqueous layer was extracted with chloroform (80 g/× twice). The obtained organic layer and extract were washed with saturated brine, combined and dried, and then concentrated under reduced pressure to obtain brown crystals, mp, 127~iao''c. Crystals with a mp of 180 to 181°C were obtained by purification with ethyl.
Pale red crystals at 41-142°C 1°4-di(methoxycarbonyl)-2-formyldihydropyrrolo(3,2-b)
1281 g of pyrrole (yield 91%) was obtained.

Elemental analysis value (as CIOHIIIN!05) HN Actual value (%) 52.98 B, 98 11.19
Calculated value (%) 52.80 4.02 11.19 Mass analysis m/e: 250 (M + 100%) pm r (C
DC13) δppm: 4.00 (8H,S), 4
．． 08 (8H, S), 6.48 (IH, dd,)J
= a, g, 0.8Hz), 7.80 (IH.

d, J=0.8Hz), 7.48(1)1. d.

J=8.8Hz), 10.87 (IH,S) Example 5 (2-acetyl-3,6-di-t-butyl-dihydropyrrolo(3,2-b)pyrrole) 10 acetic anhydride and 1 m acetic acid
3.6-di-t-butyl-dihydropyrrolo(3,2-b)virol 72.3 μ (0,332
mmol) was added thereto, and the mixture was heated under reflux for 6 hours under a nitrogen atmosphere.

The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography. There are two types of components eluted with the ethyl acetate-hexane mixed solvent, 1-acetyl form (
(yield 10%) was eluted first, then 2-acetyl-3,
6-di-t-butyl-dihydropyrrolo(3,2-b)pyrrole was eluted.

The yield of the 2-acetyl compound was 51.7 μm (yield 60%), and it was recrystallized from hexane to yield mp, 151-152°C.
A pale purple crystal of was obtained.

Claims (2)

[Claims] (1) General formula (I) ▲Mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, R_1 is a hydrogen atom, a lower alkyl group, or a lower alkoxycarbonyl group, and R_2 is a hydrogen atom, a lower alkyl group, or an aralkyl group. or aryl group, R_3 represents a hydrogen atom, lower alkyl or trialkylsilyl group). (2) General formula (II) ▲Mathematical formulas, chemical formulas, tables, etc.▼(II) (In the formula, R_1 is a hydrogen atom, a lower alkyl group, or a lower alkoxycarbonyl group, and R_3 is a hydrogen atom, a lower alkyl group, or a The general formula (I) is characterized by acylating a dihydropyrrolopyrrole compound represented by (representing an alkylsilyl group) with an acylating agent. There are mathematical formulas, chemical formulas, tables, etc. R_1 and R_3 have the same meanings as above, and R_2 represents a hydrogen atom, a lower alkyl group, an aralkyl group, or an aryl group.