JPH107614A - 2,2-bishalomethylalkanecarboxylic acid halide compound and its production - Google Patents

Abstract

PROBLEM TO BE SOLVED: To efficiently and simply produce the subject compound useful as a synthetic intermediate for yellow couplers for color photographic materials or germicides by reacting a specific OH-containing carboxylic acid compound with a specified halogen compound. SOLUTION: (A) A compound represented by the formula [R is a (cyclo)alkyl or an aryl] is reacted with (B) (B1 ) a bromide or an iodide of tri- or pentavalent phosphorous such as a compound represented by the formula PX3 (X is bromine or iodine) or R'3 R''PX [R' is an alkyl, an aryl(oxy), an alkoxy or X; R'' is an imide group or X] or (B2 ) a thionyl halide to produce a 2,2- bishalomethylalkanecarboxylic acid halide compound. Furthermore, the reaction is carried out by using the component B in an equiv. amount of 1-20 times, preferably 1-5 times based on the component A suitable at 50-200 deg.C, preferably at 100-150 deg.C temperature.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a 2,2-bishalomethylalkanecarboxylic acid halide compound which is an important synthetic intermediate for producing a yellow coupler for a color photographic light-sensitive material or a fungicide or a fungicide. It relates to the manufacturing method.

[0002]

2. Description of the Related Art Among 2,2-bishalomethylalkanecarboxylic acid halide compounds, R 2 is known.
= CH ₃ , X ¹ = X ² = X ³ = Cl, R = C ₂ H ₅ , X ¹ = X ² = X ³ = Cl, R = CH ₃ ,
X ¹ = X ² = X ³ = F and the like, and is a synthetic intermediate of a compound used as a fungicide or a fungicide (JP-A-6
2-286950, JP-A-60-42346).

Typical examples of the synthesis of conventional 2,2-bischloromethylalkanecarboxylic acid halide compounds and 2,2-bisfluoromethylalkanecarboxylic acid halide compounds are shown below. First, an inorganic acid chloride is allowed to act on an oxetane-3-carboxylic acid compound or a 2,2-bishydroxymethylalkanecarboxylic acid compound to synthesize a 2,2-bischloromethylalkanecarboxylic acid chloride compound. Thereafter, a method of exchanging halogen for a fluorine atom has been adopted.

[0004]

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However, it is difficult to efficiently synthesize a compound in which X ¹ and X ² are a bromine atom or an iodine atom by these conventional methods. There are almost no known examples of compounds in which X ¹ and X ² are a bromine atom or an iodine atom. Further, the compound is considered to be useful as a synthetic intermediate of a yellow coupler for a color photographic light-sensitive material having a cyclopropane skeleton. As a method for synthesizing a yellow coupler for a color photographic light-sensitive material having a cyclopropane skeleton, there is the following route. JP-A-4-218042

[0006]

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(Ar represents an aromatic ring which may be substituted at a substitutable position with a functional group which can be a substituent.) JP-A-7-242061

[0008]

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However, all of these synthesis methods require multiple steps and cannot be said to be efficient. As a method for efficiently producing a yellow coupler having a cyclopropane skeleton for a color photographic light-sensitive material in a short process, a method utilizing a reductive cyclization reaction of dihalide as described below has been found.

[0010]

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In order to carry out this reductive cyclization reaction, X ¹ and
X ² must be a bromine atom or an iodine atom, and when X ¹ and X ² are chlorine atoms, the cyclization reaction is inhibited. Therefore, it has been necessary to develop a method for efficiently synthesizing a 2,2-bishalomethylalkanecarboxylic acid halide compound in which X ¹ and X ² are a bromine atom or an iodine atom.

[0012]

SUMMARY OF THE INVENTION An object of the present invention is to use a compound which is easily available as a starting material in a short step to efficiently produce a yellow coupler or a fungicide or a fungicide for a color photographic light-sensitive material. 2,2-
An object of the present invention is to provide a bishalomethylalkanecarboxylic acid halide compound and a method for producing the same.

[0013]

The object of the present invention is to provide (1) a bromide or iodide of a 2,2-bishydroxymethylalkanecarboxylic acid compound represented by the general formula (I) and trivalent or pentavalent phosphorus, Alternatively, the reaction is carried out in the presence or absence of a thionyl halide in the presence or absence of a solvent.
A method for producing a bishalomethylalkanecarboxylic acid halide compound,

[0014]

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(In the formula, R represents an alkyl group, a cycloalkyl group, or an aryl group.)

[0016]

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(Wherein, R has the same meaning as in general formula (I), and X ¹ , X ² and X ³ represent a bromine atom or an iodine atom.)

(2) 2,2 represented by the general formula (III)
Wherein a bishalomethylalkanecarboxylic acid compound is reacted with a trivalent or pentavalent phosphorus halide or a thionyl halide in the presence or absence of a solvent; A method for producing the represented 2,2-bishalomethylalkanecarboxylic acid halide compound,

[0019]

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(Wherein, R has the same meaning as in general formula (I), and X ¹ and X ² represent bromine or iodine.)

[0021]

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(Wherein, R has the same meaning as in general formula (I), X ¹ and X ² represent a bromine atom or an iodine atom, and X ⁴ represents a chlorine atom, a bromine atom or an iodine atom.)

(3) 2,2- represented by the general formula (IV)
This has been achieved by providing a bishalomethylalkanecarboxylic acid halide compound.

[0024]

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(Wherein, R has the same meaning as in formula (I), X ¹ and X ² represent a bromine atom or an iodine atom, and X ⁴ represents a chlorine atom, a bromine atom or an iodine atom.)

[0026]

BEST MODE FOR CARRYING OUT THE INVENTION The compound of the present invention and the production method will be described in detail. First, the compounds will be described in detail.

In the general formulas (I) to (IV), R is preferably a linear or branched alkyl group having 1 to 20 carbon atoms (eg, methyl, ethyl, i-propyl, benzyl); Cycloalkyl groups (eg, cyclopentyl,
Cyclohexyl), an aryl group having 6 to 30 carbon atoms (for example, phenyl and naphthyl), and these substituents further include a halogen atom (for example, a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom) and an alkyl group having 1 to 8 carbon atoms. Groups (e.g., methyl, ethyl, propyl), C3-C10 cycloalkyl groups (e.g., cyclopentyl, cyclohexyl), C6-C15 aryl groups (e.g., phenyl,
Naphthyl) and the like.

R is more preferably an alkyl group having 1 to 8 carbon atoms or an aryl group having 6 to 15 carbon atoms, further preferably an alkyl group having 1 to 8 carbon atoms, and particularly preferably an ethyl group.

In the general formulas (II), (III) and (IV), X ¹ and X ² represent a bromine atom or an iodine atom, preferably a bromine atom. In the general formula (II), X ³ represents a bromine atom or an iodine atom, and preferably represents a bromine atom. In the general formula (IV), X ⁴ represents a chlorine atom, a bromine atom or an iodine atom. X ⁴ is preferably a chlorine atom or a bromine atom, particularly preferably a bromine atom.

Next, the production method of the present invention will be described in detail.
The 2,2-bishydroxymethylalkanecarboxylic acid compound (general formula (I)) used in the present invention is a readily available compound, and is typically represented by Monatsh. Chem. 88, 1099.
Compounds can be synthesized according to the method described in (1957).

The compound represented by the general formula (I) is
Reacting in the presence or absence of an agent and a solvent
2,2-bishalomethylalkanecarboxylic acid
Can be converted into the general formula (II). C
PX_Three, R '_ThreePhosphorus compounds such as R''PX
(X represents a bromine or iodine atom, and R 'is an alkyl
Group, aryl group, alkoxy group, aryloxy group,
Represents a bromine atom or an iodine atom, R '' is an imide group,
Represents a bromine or iodine atom. ) And SOX _Two (X is odor
Represents an elemental atom or an iodine atom. ) And PX
_Three , R '_ThreePX_Two, SO_X2And the like, particularly Ph._ThreePX_Two , SOX
_TwoIs preferred. The amount of these halogenating agents used is represented by the general formula
1 to 20 equivalents to the compound represented by (I),
Preferably, it is 1 to 5 equivalents. When using a reaction solvent
In the case, aromatic hydrocarbons such as toluene and chlorobenzene
Elemental solvents, acetonitrile, dimethylformamide, etc.
Is preferably used. A suitable reaction temperature is 50 to 200 ° C.
Here, 100 to 150 ° C. is preferable.

Next, a method for synthesizing the 2,2-bishalomethylalkanecarboxylic acid halide compound represented by the general formula (IV) will be described. The 2,2-bishalomethylalkanecarboxylic acid compound represented by the general formula (III) is described in Monatsh. Chem.
It can be synthesized by referring to the method of 1099 (1957).

By reacting the compound represented by the general formula (III) with a halogenating agent, 2,2-bishalomethylalkanecarboxylic acid halide compound (IV) is obtained. Here, as the halogenating agent, a phosphorus compound such as PX ₃ or R ′ ₃ R ″ PX (X represents a chlorine atom, a bromine atom or an iodine atom, and R ′ represents an alkyl group, an aryl group, an alkoxy group, an aryloxy group , A chlorine atom, a bromine atom or an iodine atom, R '' represents an imide group, a chlorine atom, a bromine atom or an iodine atom.) Or SOX ₂ (X represents a chlorine atom,
Represents a bromine or iodine atom. ) Can be used, and SOBr ₂ and SOCl ₂ are preferred. According to this method, it is possible to synthesize a compound represented by the general formula (IV) in which X ^1, X ² and X ⁴ are different from each other as compared with the case where the compound represented by the general formula (I) is used as a starting compound. It is.

Next, specific examples of compounds that can be synthesized by the method of the present invention will be shown, but the present invention is not limited to these.

[0035]

[Table 1]

[0036]

[Table 2]

[0037]

[Table 3]

[0038]

[Table 4]

[0039]

Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples. Example 1 Triphenylphosphine 1 in 500 ml of chlorobenzene
57 g was added, and 97 g of bromine was added dropwise over 1 hour at room temperature under a nitrogen atmosphere. After completion of the dropwise addition, the mixture was stirred at room temperature for 0.5 hour, and then treated with 30 g of 2,2-bishydroxymethylbutanoic acid.
In addition, the mixture was heated under reflux for 6 hours. The viscous liquid obtained after distilling off as much solvent as possible is carefully added to hexane to form a solid. This solid was filtered, and the obtained filtrate was concentrated and distilled under reduced pressure (1 mmHg) to give 120 to 1
At a temperature of 30 ° C., 50 g (74% yield) of 2,2-bisbromomethylbutanoic bromide were obtained.

Mp 57-58 ° C. ¹ H NMR (CDCl ₃ ) δ 0.97 (t, J = 7.5 Hz, 3H), 1.92 (q, J =
7.5Hz, 2H), 3.67 (d, J = 10.8Hz, 2H), 3.82 (d, J = 1
(0.8Hz, 2H)

Example 2 17 g of 2,2-bishydroxymethylbutanoic acid and DMF
At room temperature, 125 g of thionyl bromide was added dropwise to 0.3 g of the mixture. After the addition was completed, the mixture was heated to 100 ° C. and stirred for 4 hours.
After stopping the heating and allowing the mixture to cool to room temperature, low boiling compounds are first distilled off under reduced pressure (20 mmHg). The pressure was further reduced to 1 mmHg, and distillation yielded 27 g of 2,2-bisbromomethylbutanoic bromide (63% yield).

Example 3 0.26 g of 2,2-bisbromomethylbutanoic acid and 1.5 ml of thionyl chloride were mixed at room temperature under a nitrogen atmosphere, and the mixture was heated under reflux for 3 hours. After distilling off excess thionyl chloride, the reaction mixture was distilled under reduced pressure to obtain 2,2-bisbromomethylbutanoic acid chloride.

Example 4 2.7 g of 2,2-bisbromomethylbutanoic acid and Ph ₃ PCl
₂ 4.0 g of chlorobenzene 10m at room temperature under nitrogen atmosphere
and heated under reflux for 30 minutes. Thereafter, chlorobenzene was distilled off, and the reaction mixture was added to hexane to remove insoluble phosphorus compounds. The solution was distilled under reduced pressure to obtain 1.0 g of 2,2-bisbromomethylbutanoic acid chloride.

2,2-bisbromomethylbutanoic acid Mp 67-68 ° C. ¹ H NMR (CDCl ₃ ) δ 0.97 (t, J = 7.5 Hz, 3H), 1.82 (q, J =
7.5Hz, 2H), 3.67 (d, J = 10.7Hz, 2H), 3.82 (d, J = 1
0.7Hz, 2H), 9.96 (bs, 1H) 2,2-bisbromomethylbutanoic acid chloride Mp 58-59 ° C ¹ H NMR (CDCl ₃ ) δ 0.96 (t, J = 7.5 Hz, 3H), 1.95 (q , J = 7.
5Hz, 2H), 3.70 (d, J = 10.8Hz, 2H), 3.82 (d, J = 10.8H
z, 2H)

Reference Example 1 Synthesis of 2,2-bisbromomethylbutanoic acid
20% aqueous hydrogen bromide solution at room temperature and zinc bromide 2
1 g was added in small portions. After the addition of zinc bromide, the mixture was heated and stirred for 20 hours while maintaining the internal temperature at 135 ° C. After stopping the heating and allowing to cool to room temperature, the organic matter was extracted with toluene, and the obtained crude product was purified by silica gel column chromatography to give 6.0 g of 2,2-bisbromomethylbutanoic acid.
(Yield 72%) was obtained.

Reference Example 2 Synthesis of ethyl 4,4-bisbromomethyl-3-oxohexanoate 30 ml of acetonitrile and 4.5 ml of triethylamine were added to 3.6 g of ethyl malonate monopotassium salt at room temperature under a nitrogen atmosphere, followed by vigorous stirring. Add anhydrous magnesium bromide little by little while adding. After the reaction mixture was stirred for 2.5 hours, 3.4 g of 2,2-bisbromomethylbutanoic bromide obtained above was added, and the mixture was stirred at room temperature overnight.
After distilling off acetonitrile under reduced pressure, dilute hydrochloric acid was added,
After acidification, it was extracted with toluene. By purifying the obtained crude product, 2.26 g (yield 68%) of ethyl 4,4-bisbromomethyl-3-oxohexanoate was obtained.

Bp. 120-122 ° C. (1 mmHg) ¹ H NMR (CDCl ₃ ) δ 0.87 (t, J = 7.5 Hz, 3H, K and
E), 1.28 (t, J = 7.1 Hz, 2.4H, K), 1.31 (t, J = 7.1
Hz, 0.6H, E), 1.76 (q, J = 7.5 Hz, 1.6H, K), 1.80 (q,
J = 7.5 Hz, 0.4H, E), 3.58 (d, J = 10.2 Hz, 0.4H,
E), 3.63 (s, 1.6H, K), 3.66 (d, J = 11.0 Hz, 1.6H,
K), 3.69 (d, J = 10.2 Hz, 0.4H, E), 3.76 (d, J = 11.
0 Hz, 1.6H, K), 4.21 (q, J = 7.1 Hz, 1.6H, K), 4.22
(q, J = 7.1 Hz, 0.4H, E), 5.00 (s, 0.2H, E), 12.6
(s, 0.2H, E) K; ketone, E: enol mixture of ketone and enol tautomers (ketone: enol = 4: 1)

Reference Example 3 Synthesis of N- (2,4-dichloro-5-dodecyloxycarbonylphenyl) -4,4-bisbromomethyl-3-oxohexanoic acid amide 4-bisbromomethyl-3-
8.6 g of ethyl oxohexanoate and 2,4-dichloro-5-
Mix 5.6 g of dodecyloxycarbonylaniline and add 3
The mixture was heated to 140 ° C. while reducing the pressure to about 0 mmHg. After 6 hours, the reaction mixture was analyzed by HPLC to find N- (2,4-dichloro-
(5-Dodecyloxycarbonylphenyl) -4,4-bisbromomethyl-3-oxohexanoic acid amide was produced in a yield of 90%.

Mp. 96-97 ° C. ¹ H NMR (CDCl ₃ ) δ 0.84 (t, J = 7.5 Hz, 3H), 0.88 (t,
J = 6.6 Hz, 3H), 1.20-1.54 (m, 18H), 1.70-1.82 (m, 2
H), 1.87 (q, J = 7.5 Hz, 2H), 3.69 (d, J = 11.1 Hz,
2H), 3.77 (s, 2H), 3.80 (d, J = 11.1 Hz, 2H), 4.32
(t, J = 6.8 Hz, 2H), 7.51 (s, 1H), 8.83 (s, 1H), 9.41
(s, 1H)

Reference Example 4 N- (2,4-dichloro-5-dodecyloxycarbonylphenyl) -4,4-bisbromomethyl-3-oxohexanoic acid amide
Dichloro-5-dodecyloxycarbonylphenyl) -3-
Synthesis of (1-ethylcyclopropyl) -3-oxopropionamide Amide N- (2,4-dichloro-5-dodecyloxycarbonylphenyl) -4,4-bisbromomethyl-3-oxohexanoamide 0.67 g Was dissolved in 20 ml of acetone, and 0.5 ml of a saturated aqueous solution of ammonium chloride was added. 0.65 g of zinc powder was added thereto, and the mixture was stirred at room temperature for 2 hours. When the reaction mixture was analyzed by HPLC, N- (2,4-dichloro-5-dodecyloxycarbonylphenyl) -3- (1-ethylcyclopropyl) -3-oxopropionamide was obtained at a yield of 9%.
The yield was 1%, and the selectivity was 95%.

Comparative Example N- (2,4-dichloro-5-dodecyloxycarbonylphenyl) -4,4-bischloromethyl-4-oxopentanoic acid amide was placed under the same reaction conditions as in Reference Example 3, but cyclized. The reaction did not proceed.

[0052]

According to the present invention, 2,2 which is an important synthetic intermediate for efficiently producing a yellow coupler or a bactericide or a fungicide for a color photographic light-sensitive material from an easily available compound in a short step and efficiently. -A bishalomethylalkanecarboxylic acid halide compound can be produced. Thus, for example, a high-performance yellow coupler for a color photographic light-sensitive material can be synthesized at low cost.

Claims (3)

[Claims] 1. A 2,2-bishydroxymethylalkanecarboxylic acid compound represented by the general formula (I) and trivalent or pentavalent
A method for producing a 2,2-bishalomethylalkanecarboxylic acid halide compound represented by the general formula (II), which comprises reacting a brominated or iodinated phosphorus or a thionyl halide. Embedded image (In the formula, R represents an alkyl group, a cycloalkyl group, or an aryl group.) (Wherein, R has the same meaning as in general formula (I),
X ¹ , X ² and X ³ represent a bromine atom or an iodine atom. ) 2. A method comprising reacting a 2,2-bishalomethylalkanecarboxylic acid compound represented by the general formula (III) with a trivalent or pentavalent phosphorus halide or thionyl halide. A method for producing a 2,2-bishalomethylalkanecarboxylic acid halide compound represented by the formula (IV). Embedded image (Wherein, R has the same meaning as in general formula (I), and X ¹
And X ² represent bromine or iodine. ) (Wherein, R has the same meaning as in general formula (I), and X ¹
And X ² represents a bromine atom or an iodine atom, and X ⁴ represents a chlorine atom, a bromine atom or an iodine atom. ) 3. A 2,2-bishalomethylalkanecarboxylic acid halide compound represented by the general formula (IV). Embedded image (Wherein, R has the same meaning as in general formula (I), and X ¹
And X ² represents a bromine atom or an iodine atom, and X ⁴ represents a chlorine atom, a bromine atom or an iodine atom. )