JPH0753511A - Production of beta-alkoxycarbonylpyrrole compound - Google Patents

Abstract

PURPOSE:To obtain the subject compound useful as an intermediate for dyes, a coloring matter-forming coupler, etc., in good yield under mild conditions by carrying out the condensing reaction of an alcohol having great steric hindrance with pyrroles using an inexpensive and readily available acid halide. CONSTITUTION:An alcohol expressed by formula I (Z is a nonmetallic atomic group required to form a ring; R1 and R2 are each substituent groups; R3 to R9 are each H, a substituent group; X is a halogen; Y is SO2 or CO; R10 is an alkyl, an aryl or an alkoxy) and pyrroles expressed by formula II are subjected to the condensing reaction in the presence of an acid halide expressed by formula III to afford a beta-alkoxycarbonylpyrrole compound expressed by formula IV. The acid halide expressed by formula III is readily available one, e.g. methanesulfonyl chloride. The compound expressed by formula IV is useful as a synthetic intermediate for dyes or a coloring matter-forming coupler in the photographic chemical field and an antiinflammatory agent in the medical field.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a .beta.-alkoxycarbonylpyrrole compound useful as a synthetic intermediate for dyes in the field of photographic chemistry, a dye-forming coupler, and as an anti-inflammatory agent in the field of medicine.

[0002]

BACKGROUND OF THE INVENTION Pyrrole compounds are described in US Pat.
396, European Patents 487111, 48
No. 8109, No. 488248, No. 491197
JP-A-4-204730 and the like, it is described as a photographic coupler, and European Patent 518238 and the like describe that it is used as a dye. Among them, those having an alkoxycarbonyl group at the β-position are cyan couplers. And excellent as a cyan dye. The present inventors have studied to synthesize these compounds by condensing a carboxylic acid compound and alcohols to obtain these compounds. There are generally many methods for condensing a carboxylic acid compound and alcohols, but when it is limited to a practical method, it is known only as a condensation method by DCC. Further, of these, the method of condensing an alcohol having a large steric hindrance (in the present invention, an alcohol having a large steric hindrance to a hydroxyl group involved in the reaction) with an acid component is further limited. Journal of Organic Chemistry (J. Org. Chem.) Volume 30 927
The method using trifluoroacetic anhydride ((CF ₃ CO) ₂ O) described on page (1965) is mentioned as one of the methods capable of condensing alcohols having large steric hindrance. Another method is to introduce a sterically hindered alkoxy group by transesterifying pyrroles having an ethoxycarbonyl group or the like in the β-position with alcohols having a large steric hindrance.

[0003]

However, in the method using trifluoroacetic anhydride, the cyclic alcohols represented by the general formula (I) described below and the general formula (II) described below are used.
Condensation of the pyrrolecarboxylic acids shown in (2) hardly occurred. Further, in the above-mentioned method by transesterification, a high temperature of 120 ° C. or more and a large amount of alcohols are required for the reaction to proceed, so the treatment becomes complicated and it cannot be said that the reaction is suitable for practical use. Met. INDUSTRIAL APPLICABILITY In the present invention, an alcohol having a large steric hindrance is used in the reaction with a carboxylic acid compound having a pyrrole ring skeleton, an inexpensive reagent is used, and the desired ester can be produced under mild reaction conditions and with a high yield. The purpose is to provide a possible method.

[0004]

Means for Solving the Problems As a result of repeated studies to solve the problems, the present inventor has found that an easily available general formula (II
It was found that by carrying out the condensation reaction using the acid halide represented by I), the desired ester compound can be obtained under mild conditions with good yield. That is, in the present invention, (1) an alcohol represented by the following general formula (I) is condensed with a pyrrole represented by the following general formula (II) using a compound represented by the following general formula (III). The present invention provides a method for producing a β-alkoxycarbonylpyrrole compound represented by the following general formula (IV).

[0005]

[Chemical 2]

(In the formula, Z represents a group of non-metal atoms necessary for forming a ring, and the non-metal atoms may be substituted with a substituent. R ₁ and R ₂ each represent a substituent, R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ and R ₉ each represent a hydrogen atom or a substituent, and R ₁ , R ₂ , R
Non-metal atoms on ₃ , R ₄ , R ₅ and Z may bond to each other to form a ring, and R ₆ and R ₇ , R ₇ and R ₈ , and R ₈ and R ₉ may bond to each other to form a ring. May be formed. When Z forms an unsaturated ring, R ₃ , R ₄ or R ₅ may contribute to the formation of the unsaturated ring. X represents a halogen atom, Y is -SO ₂ - represent or -CO-. R ₁₀ represents an alkyl group, an aryl group or an alkoxy group. )

The present invention will be described in detail below. R
₁ and R ₂ represent a substituent other than a hydrogen atom. R ₃ , R
₄ , R ₅ , R ₆ , R ₇ , R ₈ and R ₉ each represent a hydrogen atom or a substituent. Examples of the substituents in R ₁ and R ₂ , and examples of the case where R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ and R ₉ are substituents include, for example, a halogen atom (for example,
Chlorine atom, bromine atom), aliphatic group (for example, 1 to 1 carbon atoms)
36 straight chain or branched chain alkyl groups, aralkyl groups,
An alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkenyl group, specifically, for example, methyl, ethyl, propyl, isopropyl, t-butyl, tridecyl, 2-
Methanesulfonylethyl, 3- (3-pentadecylphenoxy) propyl, 3- {4- {2- [4- (4-hydroxyphenylsulfonyl) phenoxy] dodecanamide} phenyl} propyl, 2-ethoxytridecyl, trifluoro Methyl, cyclopentyl, 3- (2,4-di-t-amylphenoxy) propyl), an aryl group (preferably having 6 to 36 carbon atoms, for example, phenyl, naphthyl,
4-hexadecoxyphenyl, 4-t-butylphenyl, 2,4-di-t-amylphenyl, 4-tetradecanamidophenyl, 3- (2,4-tert-amylphenoxyacetamido) phenyl), heterocyclic group ( For example, 3-pyridyl, 2-furyl, 2-thienyl, 2-pyridyl, 2-pyrimidinyl, 2-benzothiazolyl),
Alkoxy group (for example, methoxy, ethoxy, 2-methoxyethoxy, 2-dodecyloxyethoxy, 2-methanesulfonylethoxy), aryloxy group (for example, phenoxy, 2-methylphenoxy, 4-tert-butylphenoxy, 2,4- Di-tert-amylphenoxy, 2-chlorophenoxy, 4-cyanophenoxy, 3
-Nitrophenoxy, 3-t-butyloxycarbamoylphenoxy, 3-methoxycarbamoylphenoxy), a heterocyclic oxy group (for example, 2-benzimidazolyloxy, 1-phenyltetrazole-5-oxy, 2
-Tetrahydropyranyloxy), an alkyl aryl or a heterocyclic thio group (eg methylthio, ethylthio, octylthio, tetradecylthio, 2-phenoxyethylthio, 3-phenoxypropylthio, 3- (4-
tert-butylphenoxy) propylthio, phenylthio, 2-butoxy-5-tert-octylphenylthio, 3-pentadecylphenylthio, 2-carboxyphenylthio, 4-tetradecanamidophenylthio,
2-benzothiazolylthio, 2,4-di-phenoxy-
1,3,4-triazole-6-thio, 2-pyridylthio), acyloxy group (eg acetoxy, hexadecanoyloxy), carbamoyloxy group (eg N
-Ethylcarbamoyloxy, N-phenylcarbamoyloxy), a silyloxy group (for example, trimethylsilyloxy, dibutylmethylsilyloxy), a sulfonyloxy group (for example, dodecylsulfonyloxy), an acylamino group (for example, acetamide, benzamide, tetradecanamide), 2 -(2,4-tert-amylphenoxyacetamide, 2- [4- (4-hydroxyphenylsulfonyl) phenoxy)] decane amide, isopentadecane amide, 2- (2,4-di-t-amylphenoxy) butanamide, 4 -(3-t-butyl-4-
(Hydroxyphenoxy) butanamide), an alkylamino group (eg, methylamino, butylamino, dodecylamino, dimethylamino, diethylamino, methylbutylamino), an arylamino group (eg, phenylamino, 2-chloroanilino, 2-chloro-5-). Tetradecanamide anilino, N-acetylanilino, 2-chloro-5- [α-2-tert-butyl-4-hydroxyphenoxy) dodecanamide] anilino, 2-chloro-5
-Dodecyloxycarbonylanilino), a ureido group (eg, methylureido, phenylureido, N, N
-Dibutylureido, dimethylureido), a sulfamoylamino group (for example, N, N-dipropylsulfamoylamino, N-methyl-N-decylsulfamoylamino), an alkenyloxy group (for example, 2-propenyloxy), Formyl group, alkyl-aryl or heterocyclic acyl group (eg acetyl, benzoyl, 2,4-di-tert-amylphenylacetyl, 3-phenylpropanoyl, 4-dodecyloxybenzoyl), alkyl-aryl or heterocyclic sulfonyl group (Eg, methanesulfonyl, octanesulfonyl, benzenesulfonyl, toluenesulfonyl), sulfinyl group (eg, octansulphinyl, dodecylsulfinyl, dodecanesulfinyl, phenylsulfinyl, 3-pentadecylphenyls Finiru, 3-phenoxypropylsulfinyl sulfinyl) alkyl, aryl or heterocyclic oxycarbonyl group (e.g., methoxycarbonyl, butoxycarbonyl, dodecyloxycarbonyl, octadecyloxycarbonyl, phenyloxycarbonyl,
2-pentadecyloxycarbonyl), alkyl aryl or heterocyclic oxycarbonylamino groups (eg methoxycarbonylamino, tetradecyloxycarbonylamino, phenoxycarbonylamino, 2,4-di-tert-butylphenoxycarbonylamino), sulfonamides Groups (eg, methanesulfonamide, hexadecanesulfonamide, benzenesulfonamide, p
-Toluenesulfonamide, octadecanesulfonamide, 2-methoxy-5-tert-butylbenzenesulfonamide), a carbamoyl group (for example, N-ethylcarbamoyl, N, N-dibutylcarbamoyl, N- (2
-Dodecyloxyethyl) carbamoyl, N-methyl-
N-dodecylcarbamoyl, N- [3- (2,4-di-
tert-aminophenoxy) propyl] carbamoyl), a sulfamoyl group (eg, N-ethylsulfamoyl, N, N-dipropylsulfamoyl, N- (2
-Dodecyloxyethyl) sulfamoyl, N-ethyl-N-dodecylsulfamoyl), N, N-diethylsulfamoyl), phosphonyl group (for example, phenoxyphosphonyl, octyloxyphosphonyl, phenylphosphonyl), sulfamide group ( For example, dipropylsulfamoylamino), an imide group (eg, N-succinimide,
Hydantoinyl, N-futylimide, 3-octadecenylsuccinimide), silyl group (for example, trimethylsilyl), azolyl group (for example, imidazolyl, pyrazolyl, 3-chloro-pyrazol-1-yl, triazolyl), hydroxy group, cyano group, Examples thereof include a carboxy group, a nitro group, a sulfo group and an unsubstituted amino group.

R ₁ and R ₂ preferably have 1 to 3 carbon atoms.
0 alkyl group, aryl group, alkoxy group, aryloxy group, halogen atom, or alkyl aryl or heterocyclic oxycarbonyl group, alkyl aryl or heterocyclic oxycarbonylamino group, acylamino group, ureido group, sulfamoylamino Represents a group, a sulfonamide group, and a silyl group. R ₁ and R ₂ are more preferably an alkyl group having 1 to 30 carbon atoms, an aryl group, an alkoxy group or an aryloxy group. R ₁ , R
₂ may be the same or different. R ₃ , R ₄ ,
R ₅ is preferably a hydrogen atom, an alkyl group having 1 to 30 carbon atoms, an aryl group, an alkoxy group, an aryloxy group, a halogen atom, or an alkyl aryl or heterocyclic oxycarbonyl group, an alkyl aryl or a heterocyclic oxycarbonylamino. Group, acylamino group, ureido group, sulfamoylamino group, sulfonamide group, silyl group. More preferably, R ₃ , R ₄ and R ₅ are alkyl groups having 3 to 30 carbon atoms,
An aryl group, an alkoxy group, and an aryloxy group.
R ₃ , R ₄ and R ₅ may be the same or different. The compounds used in the present invention may have stereochemical isomers with respect to R _{1 to} R ₅ , but when the compounds of the present invention are used, a mixture of these isomers may be used, or a single isomer may be used. It may be an isomer.

In the general formula (I), Z represents an atom or an atomic group necessary to form a 4-membered ring or more, preferably a 5-membered to 8-membered ring together with a carbon atom to be bonded, and a divalent group forming the ring. Represents a divalent amino group, an ether bond, a thioether bond, an alkylene group, an alkenylene group, an imino group, a sulfonyl group, a carbonyl group, etc., and a plurality of these may be combined, and these have a substituent. May be. Here, as the substituent, there are R _{3 to} R ₉ mentioned above.
Specific groups mentioned in the above. The divalent group forming a ring is preferably a divalent amino group, an ether bond, a thioether bond, an alkylene group, an alkenyl group or an imino group, and more preferably an alkylene group or an alkenylene group.

R ₈ is preferably a hydrogen atom, a halogen atom, a heterocyclic group, an alkoxy group, an aryloxy group,
Alkylthio group, arylthio group, heterocyclic oxy group,
Examples thereof include an azo group, an acyloxy group, a carbamoyloxy group, a heterocyclic thio group and an azolyl group. R ₉
Preferably as cyano group, nitro group, carboxy group,
Examples thereof include a sulfo group, a carbamoyl group, a sulfamoyl group, a sulfonyl group, an alkoxycarbonyl group, a sulfinyl group, an aryloxycarbonyl group and an acyl group. The ring which may be formed by combining R ₆ and R ₇ is a group represented by the following chemical formula 3, and the ring which may be formed by combining R ₇ and R ₈ is represented by the chemical formula 4. There is a group

[0011]

[Chemical 3]

[0012]

[Chemical 4]

R ₁₀ represents an alkyl group, an aryl group or an alkoxy group, preferably an alkyl group or an aryl group. X represents a halogen atom (for example, chlorine, bromine or iodine atom), and preferably a chlorine atom. Y is -SO
₂ - or represents -CO-, preferably -SO ₂ - is. The following are specific examples of the compound (III).

[0014]

[Chemical 5]

Further, acetyl bromide, acetyl iodide, methanesulfonyl bromide, methanesulfonyl fluoride and the like can be mentioned. Next, specific examples of the condensate that can be synthesized by the method of the present invention will be shown, but the condensate is not limited thereto.

[0016]

[Chemical 6]

[0017]

[Chemical 7]

[0018]

[Chemical 8]

[0019]

[Chemical 9]

In the present invention, the reaction molar ratio between the alcohol represented by the general formula (I) and the pyrrole represented by the general formula (II) depends on the stoichiometric amount, but preferably 1
It is 0: 1 to 1: 1 and more preferably 5: 1 to 2: 1. The amount of the compound of the general formula (III) used is about 1 mol or more, preferably 1.5 to 3 mol per 1 mol of the compound of the general formula (I). In the method of the present invention, the reaction is preferably carried out in the presence of a base. Examples of such a base include trialkylamine (eg, triethylamine), 1,8-diazabicyclo [5.4.0] -7-undecene, and 4-dimethylaminopyridine, preferably triethylamine. As the solvent, a nonpolar solvent is preferable, and a solvent such as toluene, ethyl acetate or methylene chloride is used. The amount of the solvent used is appropriately 5 to 50 times, preferably 10 to 30 times by weight that of the compound of the general formula (I).

The amount of the base used is appropriately about 1.2 to 5 molar equivalents, preferably 1.5 to 2.5 molar equivalents, relative to the compound of general formula (I). Reaction temperature is usually -40
-80 degreeC, Preferably it is 20-60 degreeC. Reagents can be added as pyrroles (II) and acid halides.
Method of adding cyclic alcohol (I) to where (III) was previously reacted with a base, and addition of base to a mixed solution of cyclic alcohol (I), pyrroles (II) and acid halide (III) There is a method, but the latter method is preferable.

[0022]

The present invention will be described in more detail based on the following examples. Example 1 (Synthesis of Exemplified Compound (2))

[0023]

[Chemical 10]

Compound (a-1) (48.7 g, 128 mm)
ol) and compound (b-1) (86.9 g, 384 mmol) in 1000 ml of ethyl acetate and 200 ml of dimethylacetamide.
Dissolve in ml of mixed solution and warm to 35 ° C. with stirring. Methanesulfonyl chloride (21.8m)
1, 282 mmol) and 4-dimethylaminopyridine (catalytic amount) were added, and triethylamine (53.5 m) was added.
1, 384 mmol) in 50 ml of ethyl acetate is slowly added dropwise. After the dropping was completed, water was added, the ethyl acetate layer was washed with water, dried and the solvent was distilled off. After distilling (b-1) off the residue under high vacuum, acetonitrile was added for crystallization to obtain 47.5 g (yield 63%) of Exemplified compound (2). The melting point of the exemplified compound (2) is 203 to 204 ° C.

Comparative Example Compound (b-1) (0.36 g, 1.58 mmol) was dissolved in acetonitrile, and trifluoroacetic anhydride (0.
(22 ml, 1.58 mmol) is added, and the mixture is ice-cooled with stirring. Compound (a-1) (0.50 g, 1.3
1 mmol) was added little by little, and after the addition was completed, the mixture was stirred at room temperature. However, the exemplified compound (2) could not be obtained.

Example 2 (Synthesis of Exemplified Compound (10))

[0027]

[Chemical 11]

Compound (a-2) (0.86 g, 3.61)
mmol) and compound (b-2) (0.83 g, 7.23 mmo
l) was dissolved in 20 ml of ethyl acetate, and methanesulfonyl chloride (0.62 ml, 7.95 mmol) was added.
4-Dimethylaminopyridine (trace amount) was added, and triethylamine (1.51 m
1, 10.8 mmol) solution dissolved in 5 ml of ethyl acetate is added dropwise. After completion of dropping, the mixture is stirred for 30 minutes, water is added, and the ethyl acetate layer is washed with water. After drying the organic layer, the solvent was distilled off. The residue was purified by silica gel chromatography to obtain 0.65 (54%) of Exemplified compound (10).

[0029]

EFFECT OF THE INVENTION According to the condensation method of the present invention, an alcohol having a large steric hindrance can be esterified with a pyrrole carboxylic acid under mild conditions using an inexpensive reagent to obtain an ester compound in good yield.

Claims (1)

[Claims] 1. An alcohol represented by the following general formula (I) and a pyrrole represented by the following general formula (II) are condensed with a compound represented by the following general formula (III). A method for producing a β-alkoxycarbonylpyrrole compound represented by the following general formula (IV): [Chemical 1] (In the formula, Z represents a group of non-metal atoms necessary for forming a ring, and the non-metal atoms may be substituted by a substituent. R ₁ and R ₂ each represent a substituent, R ₃ , R
₄ , R ₅ , R ₆ , R ₇ , R ₈ and R ₉ each represent a hydrogen atom or a substituent, and R ₁ , R ₂ , R ₃ , R ₄ , R ₅
And non-metal atoms on Z may be bonded to each other to form a ring, and R ₆ and R ₇ , R ₇ and R ₈ , and R ₈ and R ₉ may be bonded to each other to form a ring. When Z forms an unsaturated ring, R ₃ , R ₄ or R ₅ may contribute to the formation of the unsaturated ring. X represents a halogen atom, and Y represents-
Represents SO ₂ — or —CO—. R ₁₀ represents an alkyl group, an aryl group or an alkoxy group. )