WO1997043041A1 - Regioselective nuclear chlorination catalyst for aromatic hydrocarbons and process for nuclear chlorination - Google Patents

Abstract

Novel phenyl 10H-phenothiazine-10-carboxylates of general formula (I), combinations of which with Lewis acids are useful as regioselective nuclear chlorination catalysts for aromatic hydrocarbons. The catalysts are advantageous in that the regioselectivity is not lowered even when the nuclear chlorination is conducted at a reaction temperature exceeding 45 °C and that the regioselectivity is enhanced with an increasing degree of chlorination. In general formula (I), x is halogeno, C1-C4 alkyl, C1-C4 alkoxy, nitro or cyano and n is an integer of 0 to 5, with the proviso that when n is 2 or above, X's may be the same or different from each other; s is an integer of 0 to 5; t is an integer of 0 to 4; and u is an integer of 0 to 4, with the proviso that the sum total of n and s is 5 or below.

Description

 Description: Catalyst for regioselective nuclear chlorination of aromatic hydrocarbons and nuclear chlorination method

 The present invention relates to a catalyst for regioselective chlorination of aromatic hydrocarbons and a method for regioselective chlorination of aromatic hydrocarbons using the same.

 [Background technology]

 Nuclear chlorinated aromatic hydrocarbons are important compounds as raw materials for polymers, pharmaceuticals and agricultural chemicals. Accordingly, various proposals have been made for a technique for nuclear chlorination of aromatic hydrocarbons with good regioselectivity.

 Among the compounds used as catalysts for the regioselective chlorination of aromatic hydrocarbons, there are the following proposals for 10-substituted-10H-phenothiazines to be mixed with Lewis acids.

JP 59 - The 206,051 discloses, 1 0-§ reel carbonyl - 1 0H- phenothiazine, 10- Harokarubo two Lou 1 0H- Fuenochia gin and _{1 0- CH T X, CO- 1} OH- phenothiazine [X is Black

 * y

 X represents 0 to 3, and y represents 1 to 3. ] Is described.

 JP-A-60-125251 describes 10-lower alkylcarbonyl 10H-phenothiazine, 10-arylcarbonyl 10H-phenothiazine and 10-haloalkylcarbonyl-1 10H-phenothiazine. Have been.

JP 4 - To 305544 _{JP, 10- CF 3 (CF 2)} n C 0 - 10H- Fuwenochiajin [n = 0, 1 or 2] is described. On the other hand, 10H-phenothiazine-10-potassium phenyl phenyl ester PT / JP97 / 01609

Is described in Chem. Ber., 111, 1453-63 (1978).

 However, as a catalyst for regioselective chlorination of aromatic hydrocarbons, there is a demand for a proposal of 10-substituted-10H-funothiazines having a new feature of being mixed with a Lewis acid.

 [Disclosure of the Invention]

 Thus, the present inventors have conducted intensive studies on various 10-substituted-1 10H-phenothiazines, which have not been reported previously, regarding regioselective chlorination of aromatic hydrocarbons. The 10-substituted 10H-funothiazines to be described in detail are found to be advantageous as catalysts for regioselective nuclear chlorination of aromatic hydrocarbons when used in combination with Lewis acids, leading to the completion of the present invention. I

 The present invention has the following structural features.

 The first invention relates to a catalyst for regioselective chlorination of aromatic hydrocarbons, and more specifically relates to 10H-phenothiazine-10-carboxylic acid fuunyl esters represented by the following formula (I): And Lewis acids.

 X n

(CI) s

(In the formula, X represents a halogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a nitro group or a cyano group,

n represents an integer of 0 to 5, and when n is greater than 2, Xs may be the same or different; s represents an integer of 0 to 5, t represents an integer of 0 to 4, u represents an integer of 0 to 4, and (n + s) is 5 or less. )

 The second invention relates to 10H-phenothiazine-10-carbonic acid phenyl esters of the following formula (I).

(In the formula, X represents a halogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a nitro group or a cyano group,

n represents an integer of 0 to 5, and when n is greater than 2, Xs may be the same or different;

s represents an integer of 0 to 5, t represents an integer of 0 to 4, u represents an integer of 0 to 4, and (n + s) is 5 or less. However, _n = s = t = u = 0 is excluded. )

 The third invention relates to a method for regioselective nuclear chlorination of aromatic hydrocarbons, which comprises, as a catalyst, 10H-phenothiazine-10-carboxylic acid phenyl ester represented by the above formula (I). Characterized in that aromatic hydrocarbons are chlorinated by using a combination of a compound and a Lewis acid.

 [Best Mode for Carrying Out the Invention]

 Hereinafter, the present invention will be described in detail.

The regioselective nuclear chlorination reaction of aromatic hydrocarbons of the present invention is a nuclear chlorination reaction of aromatic hydrocarbons serving as a substrate on a benzene ring, wherein a specific reaction is carried out for a substituent already existing. In the position of, means a reaction that selectively nucleates nucleus. For example, in nuclear chlorination, it means a para-selective chlorination reaction in benzene and toluene, which exhibit ortho and para orientation.

 Examples of the substituent already existing in the aromatic hydrocarbon include a halogen atom selected from fluorine, chlorine, bromine and iodine, an alkyl group having 1 to 6 carbon atoms, preferably methyl, ethyl, propyl, Alkyl groups having 1 to 4 carbon atoms, including 1-methylethyl and 1,1-dimethylethyl, and alkoxy groups having 1 to 6 carbon atoms, preferably carbon atoms including methoxy, ethoxy, propoxy and (1-methylethyl) oxy Examples thereof include an alkyloxy group having 1 to 4 carbon atoms, an alkylthio group having 1 to 6 carbon atoms, and preferably an alkylthio group having 1 to 4 carbon atoms including methylthio and ethylthio.

Five.

 The aromatic hydrocarbons to be nuclear-chlorinated according to the present invention are those in which the benzene ring is substituted with one to three of the above substituents. Further, a part of the alkyl group having 1 to 6 carbon atoms as a substituent may form a ring by a single bond with the ortho position on the benzene ring, and may form a hetero atom such as oxygen or sulfur. And may combine with each other to form a ring.

 Further, a part of the alkoxy group having 1 to 6 carbon atoms or a part of the alkylthio group having 1 to 6 carbon atoms as a substituent may form a ring by a single bond with the ortho position on the benzene ring. Also, they may be bonded via a heteroatom such as oxygen or sulfur to form a ring.

 In the above, a compound consisting of a benzene ring and a ring containing oxygen and sulfur fused to the benzene ring is usually classified as a heterocyclic compound and is distinguished from aromatic hydrocarbons. However, these compounds are also defined as being included in the range of aromatic hydrocarbons as modified substituents on the benzene ring.

Also, the same substituents such as benzene and p-xylene are in the p-position. Nuclear chlorination, in which the first chlorine atom is introduced, such as a bonded benzene compound, does not show regioselectivity structurally, but nuclear chlorination, in which the second chlorine atom is introduced, does not. Aromatic hydrocarbons that exhibit selectivity can also be used as substrates in the present invention.

 The 10 H-phenothiazine-10-carboxylic acid phenyl esters represented by the formula (I) used as a catalyst in the present invention are, for example, substituted as defined in JP-A-59-26051. It has the structural similarity to a compound having a group, and 10-benzoyl-10H-phenothiazine described in JP-A-60-125251. However, the compound represented by the formula (I) is a compound having a substituent having a structure in which an oxygen atom is inserted between the phenyl group and the carbonyl group of the benzoyl group at the 10-position. Nzoruil 10 H—Phenothiazines differ in structure. Therefore, the present invention is a novel invention, since no proposal has been made on regioselective nuclear chlorination using the compound represented by the above formula (I) of the present invention.

 Furthermore, the compounds of the present invention represented by the formula (I) show that the regioselectivity of nuclear chlorination thereby is unexpectedly large from the structurally similar 10-benzoyl 10H-phenothiazine. Has advantages. Furthermore, the regioselectivity of nuclear chlorination by the compound represented by the formula (I) does not decrease even when nuclear chlorination is performed at a reaction temperature exceeding 45 ° C. Further, as the degree of chlorination (the number of moles of chlorine substituted with 1 mole of aromatic hydrocarbons as a substrate in the nuclear chlorination reaction of the present invention) is increased, the regioselectivity is improved.

These advantages are also one of the features of the compound represented by the formula (I) found by the present inventors. As a result, according to the present invention, it is possible to use a substrate having a high melting point or to carry out a nuclear salinization reaction for producing a product having a high melting point. Thus, nuclear chlorination with a high degree of chlorination is possible without fear of solidification during the reaction, and heat of reaction is easily removed.

 The compound represented by the formula (I) of the present invention is composed of 10H-phenothiazines (11) and phenyl chloroformates (111) as shown in the following reaction formula. Chem. Ber., 11 1 , 1453-63 (1 978) (10 H-phenothiazine and phenyl chloroformate in benzene or xylene. It can be produced by an operation in accordance with the method described in).

+

 Χη

 C I COO

 (C I) s

式 （ I) において、 所望する値の s、 tおよび uを有する化合物は、 上記反応式のように、 所望する値の tおよび Uを有するフユノチアジン 類 （II) および所望する値の sを有するクロロギ酸フユニル類 （111 ) から誘導することができる。 さらに、 所望する値より少ない値の s、 t および uを有する化合物 （ I) を、 核塩素化 （通常は、 塩素または塩化 スルフリルと、 ルイス酸とを使用する。 ） によって、 所望する値の s、 tおよび uを有する化合物 （ I) に誘導することもできる。 D s

In the formula (I), the compound having the desired values of s, t and u is, as shown in the above reaction formula, a fuunothiazine (II) having the desired values of t and U and a chloroform having the desired value of s. It can be derived from acid humylates (111). In addition, compounds (I) having less than the desired values of s, t and u can be converted to the desired values of s by nuclear chlorination (usually using chlorine or sulfuryl chloride and a Lewis acid). , T and u can also be derived.

 As for n in the compound represented by the formula (I), 0 or 1 is preferable.

 X is preferably a halogen atom, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms, and more preferably a fluorine atom, a chlorine atom, a methyl group and a methoxy group. s is preferably an integer of 0 to 2, and t and u are each preferably an integer of 0 to 3.

 If the substituents contained in the combination of these preferred definitions together with the bonding positions are shown for the phenothiazine ring of the compound represented by the formula (I), non-dew (t = u = 0), 2-black mouth, 2,8-diclo mouth, 1,2,8-trichloro, 2,3,8-triclo mouth, 2,4,8-tricro mouth, 1,2,7,8-tetraclo mouth , 2, 4.7.8-tetracloth and 2,3,4,7.8-pencloth. For the phenyl group, unsubstituted (n = s = 0), 4-fluoro, 4-chloro, 4-methyl and 4-methoxy can be mentioned.

 The nuclear chlorination of the present invention requires the use of a Lewis acid. The Lewis acid used may be a Lewis acid generated in a reaction system from a metal element or a compound having the metal element as a constituent element.

In the present invention, among the Lewis acids, ferric chloride, aluminum chloride It is preferred to use at least one Lewis acid selected from the group consisting of antimony and antimony trichloride.

 In the present invention, benzene is used as the aromatic hydrocarbon as the substrate to be chlorinated in the present invention, since benzene formed in the reaction system from benzene is the substrate of the present invention, and benzene can also be used as the substrate. , Toluene,

0-xylene, p-xylene (1-chloro-2.5-dimethylbenzene generated from p-xylene in the reaction system is the substrate of the present invention, p-xylene can also be used), Preferably, at least one selected from the group consisting of toluene and o-dichlorobenzene and 1-chloro-2,5-dimethylbenzene is used.

 In the nuclear chlorination reaction of the present invention, chlorobenzene, dichlorobenzene, cyclotoluene, 1,2-dichloroethane, 1,2-dichloropropane, dichloromethane, chloroform, Halogenated hydrocarbons such as carbon chloride can be used as the reaction solvent.

 Further, the above-mentioned aromatic hydrocarbons and the above-mentioned halogenated hydrocarbons which are substrates can also be used as a solvent in a nuclear chlorination reaction of the compound represented by the formula (1).

 In the nuclear chlorination reaction of the compound represented by the formula (I), the nuclear chlorinated isomer formed depends on the use ratio of the solvent and Z or Lewis acid to the compound of the formula (I) and the reaction conditions such as the chlorination rate. Can be controlled. For example, using a Lewis acid in an amount such that the molar ratio of the compound of formula (1) / ^ Lewis acid is 1-3 (preferably 1.5-2), the concentration of the compound of formula (I) If the nuclear chlorination reaction is carried out using an amount of a solvent that gives a concentration lower than 0.5% (preferably 2%), chlorine will also bind to position 1 of the phenothiazine ring. Can give priority to the generation of certain isomers.

The nuclear chlorination reaction of the compound represented by the formula (I) is usually carried out by fuunothiazine The reaction is carried out using a compound in which the ring portion is unsubstituted [compound (t = u = o)]. The method for selective nuclear chlorination of the present invention is characterized in that the reaction is carried out by using the compound represented by the formula (I) and Lewis acids in combination as a catalyst. The product is removed by distillation, the substrate is added again to the supernatant, and the substrate is re-added, and a nuclear reaction is performed by a repeated reaction method, or a part of the reaction mixture is added to the substrate to perform the nuclear chlorination. Reaction methods are also possible. In the case of these reaction methods, the compound represented by the formula (I) and / or Lewis acids may be added during the reaction step.

 In the present invention, the amount (millimol) of the Lewis acid to be used per 1 mol of the aromatic hydrocarbon as the substrate is from 0.03 to 6, preferably from 0.09 to 4, more preferably from 0.15 to 3 It is.

 The amount of the compound represented by the formula (I) to be used per 1 mol of the Lewis acid (millimol) is from 0.3 to 20, preferably from 0.6 to: L5, and more preferably from 1 to 5. : L 0.

 The nuclear chlorination in the present invention is carried out using a necessary or excess amount of gaseous or liquid chlorine, and is reacted in an amount corresponding to the following degree of chlorination.

 The chlorination degree (in the nuclear chlorination reaction of the present invention, the number of moles of chlorine replaced by 1 mole of aromatic hydrocarbons as a substrate) is from 0.2 to 1.5, preferably from 0.3 to 1. 2, more preferably 0.4-1. Therefore, when benzene p-xylene is used as a substrate, the chlorination degree is 1.2

~ 2.5, preferably 1.3-2,2, more preferably 1.4-2, by nuclear chlorination up to the chlorination degree obtained by adding 1 to the above range. The position selectivity of the invention becomes remarkable.

The reaction temperature in the present invention is preferably from 1 to 90 ° C, more preferably from 45 to 75 ° C. [Example]

 Hereinafter, the present invention will be described with reference to Examples, but the present invention is not limited thereto.

^[ The abbreviations of the 1 H NMR terms have the following meanings.

s (—double line), d (double line), m (multiple line), d d (double double line). The numbers following d and d d indicate coupling constants (unit: Hz).

Production Example 1

 (Nucleochlorination of benzene at the mouth)

 [As a catalyst, ferric chloride is used in combination with 10H-phenothiazine 10-phenylphenyl carboxylate (used in Reference Production Example 1 below)]

 To 246 g (2.19 mol) of benzene in a light-shielded reactor at room temperature. * Under stirring, 0.47 g (2.9 mmol) of ferric chloride and 10 OH of 1OH-phenothiazine 4.7 g (14.7 millimoles) of phenyl ribonate were added. Then, the temperature of the mixture was raised to 50 ° C, gaseous chlorine was blown at the same temperature, and over 7 hours, the chlorination degree was 0.48 based on the benzene at the outlet. Chlorinated to 48). When the reaction mixture was analyzed by gas chromatography, it was confirmed that the mixture had the following composition. Parentheses indicate the content (%) of each component.

 Benzene (44.92), o-dichlorobenzene (7.34), m-dichlorobenzene (0.05), p-dichlorobenzene

 (47.66), Tri-mouth benzene (0.04)

The value of {p ÷ (o + p) X 100} calculated from the above composition was 87 (%). Production Example 2

 (Nuclear chlorination of benzene)

 [As a catalyst, ferric chloride is used in combination with 10H-phenothiazine-10-potassium phenyl carboxylate (used in Reference Production Example 1 below)]

 ① At room temperature, with stirring, add 150 g (1.92 mol) of benzene and 0.06 g (0.37 mmol) of ferric chloride and 1 OH-phenothiazine 10-carbon 0.179 g (0.56 mimol) of the acid phenyl ester was added. Then, the temperature of the mixture was raised to 60, and gaseous chlorine was blown at the same temperature, and chlorination was performed over 5.5 hours to a chlorination degree of 1.59 based on benzene. The reaction mixture was analyzed by gas chromatography, and it was confirmed that the reaction mixture had the following composition. The parentheses indicate the content () of each component.

 Benzene (0.04), benzene (35.05), o-dichlorobenzene (8.85), m-dichlorobenzene (0.07), p-dichlorobenzene (55.93) The value of {p ÷ (o + p) xl00} calculated from the above composition was 86 (%).

 (2) The reaction mixture of (1) was chlorinated at 60 and further over 4.5 hours to a chlorination degree of 1.96 based on benzene. When the reaction mixture was analyzed by gas chromatography, it was confirmed that the mixture had the following composition. Parentheses indicate the content (%) of each component.

 Benzene (0), benzene (3.11), o-dichlorobenzene (1.89), m-dichlorobenzene (0.08), p-dichlorobenzene (84.8) , Tri-mouth benzene (0.12)

The value of {p + (o + p) x 100} calculated from the above composition is 88 (%) Met.

Production Example 3

 (Nuclear chlorination of benzene)

 [As a catalyst, ferric chloride is used in combination with 10H-phenothiazine-10-carboxylic acid (4-chlorofurnyl) ester (prepared in Production Example 8 below)]

 To 150 g (1.92 mol) of benzene in a light-shielded reactor at room temperature, 0.12 g (0.74 mol) of ferric chloride and 1 OH-phenothiazine 10- 0.524 g (1.48 millimoles) of sulfonic acid (4-chlorophenyl) ester were added. Then, the temperature of the mixture was raised to 50 ° C, gaseous chlorine was blown at the same temperature, and chlorination was performed over 9 hours to a chlorination degree of 1.84 based on benzene. Analysis of the reaction mixture by gas chromatography confirmed that the reaction mixture had the following composition. Parentheses indicate the content (%) of each component.

 Benzene (0.01), benzene (13.13), o-dichlorobenzene (1.74), m-dichlorobenzene (0.08), p-dichlorobenzene ( 74. 89), and the benzene (0.14) value of {p + (o + p) X 100} calculated from the above composition was 86 (%).

Production Example 4

 (Nuclear chlorination of benzene)

 [As a catalyst, ferric chloride is used in combination with 10H-phenothiazine 10-carboxylic acid (4-methylphenyl) ester (the one prepared in Production Example 9 below)]

To 150 g (1.92 mol) of benzene in a light-shielded reactor at room temperature, 0.12 g (0.74 mmol) of ferric chloride and 10 H— Phenothiazine 10-Rubonic acid (4-methylphenyl) ester 0.

493 g (1.48 mimol) were added. Then, the temperature of the mixture was raised to 50 ° C, and gaseous chlorine was blown at the same temperature, and chlorination was performed over 9 hours to a chlorination degree of 1.75 based on benzene. Analysis of the reaction mixture by gas chromatography confirmed that the reaction mixture had the following composition. Parentheses indicate the content (%) of each component.

 Benzene (0.02), benzene (20.53), o-cyclobenzene (13.73), m-cyclobenzene (0.12), p-cyclobenzene (65.49), Trimethylbenzene (0.1) The value of {p ÷ (o + p) x 100} calculated from the above composition is 83

(%) Met.

Production Example 5

 (Nuclear chlorination of benzene)

 [As a catalyst, ferric chloride is used in combination with 10H-phenothiazine- 10-hydroxycarboxylic acid (4-methoxyphenyl) ester (used in Production Example 10 below)]

 At room temperature, add 150 g (1.92 mol) of benzene and 0.12 g (0.74 mimol) of ferric chloride and 10 H-phenothiazine- 10-butane in a light-tight reactor under stirring. 0.517 g (1.48 mmol) of the acid (4-methoxyphenyl) ester was added. Then the temperature of the mixture

The temperature was raised to 50 ° C, gaseous chlorine was blown at the same temperature, and chlorination was performed over a period of 8 hours to a chlorination degree of 1.58 based on benzene. The reaction mixture was analyzed by gas chromatography, and it was confirmed that the reaction mixture had the following composition. Parentheses indicate the content (%) of each component.

Benzene (0.09), benzene (35.71), 0—dichlorobenzene (1.41), m-dichlorobenzene (0.14), p The values of {p + (o + p) x 100} calculated from the above composition are as follows: dichloro-mouth benzene (52.54), tricyclo-mouth benzene (0.11)

(%) Met.

Production Example 6

 (Nuclear chlorination of benzene)

 [As a catalyst, ferric chloride is used in combination with 2-chloro-10H-phenothiazine-10-potassium phenyl carboxylate (the one produced in Production Example 11 below)]

 To a solution of 150 g (1.92 mol) of benzene in a light-shielded reactor at room temperature was added 0.06 g (0.37 mimol) of ferric chloride and 2 2 0.196 g (0.56 mimol) of phenothiazine-phenyl sulfonic acid phenyl ester was added.

 Then, the temperature of the mixture was raised to 60 ° C., gaseous chlorine was blown in at the same temperature, and the mixture was chlorinated over 7.0 hours to a chlorination degree of 1.5 based on benzene. The reaction mixture was analyzed by gas chromatography, and it was confirmed that the mixture had the following composition. Parentheses indicate the content (%) of each component.

 Benzene (0.25), benzene (4.27), o-dichlorobenzene (8.73), m-dichlorobenzene (0.11), p-dichlorobenzene (48.56) ), Trichloromouth benzene (0.07) The value of {P ÷ (o + p) X100} calculated from the above composition was 85 (%).

Production Example 7

 (Nuclear chlorination of benzene)

[As a catalyst, a ferric chloride and a nuclear chlorinated product of 10H-phenothiazine-110-potassium fuunyl ester (obtained in (A) of Production Example 12 below) Used part of the reaction mixture)

 At room temperature, in a light-shielded reactor, 144 g (1.84 mol) of benzene, under stirring, 0.05 g (0.308 mmol) of ferric chloride and the reaction mixture obtained in Production Example 9 9.92 g of 287 g [The amount of the mixture used includes 0.016 g (0.097 mimol) of ferric chloride and 10H-phenothiazine in the nuclear chlorination starting material of Production Example 9. 0.10 g of phenyl carboxylate] (0.49 mmol). Then, the temperature of the mixture was raised to 60 ° C, and gaseous chlorine was blown at the same temperature, and chlorination was performed over 3.5 hours to a chlorination degree of 1.72 based on benzene. When the reaction mixture was analyzed by gas chromatography, it was confirmed that the mixture had the following composition. Parentheses indicate the content (%) of each component.

 Benzene (0.01), benzene (23.29), o-dichlorobenzene (1.107), m-dichlorobenzene (0.14), p-dichlorobenzene (65.39), Trichloromouth benzene (0.11) The value of {p + (o + p) xl00} calculated from the above composition was 86 (%).

Comparative Production Example 1

 (Nuclear chlorination of benzene)

 [As a catalyst, ferric chloride is used in combination with 10-benzylazo 10H-phenothiazine (used in Reference Production Example 2 below)]

To a mixture of 1.50 g (1.92 mol) of benzene in a light-shielded reactor at room temperature, 0.12 g (0.74 mmol) of ferric chloride and 10-benzoyl-10H-phenothiazine under stirring. 0.499 g (1.48 mimol) was added. Then, the temperature of the mixture was raised to 50 ° C, gaseous salt cable was blown at the same temperature, and the salting degree was 1.58 based on benzene over 7 hours. Chlorinated until. When the reaction mixture was analyzed by gas chromatography, it was confirmed that the mixture had the following composition. Parentheses indicate the content (%) of each component.

 Benzene (0.14), benzene (34.97), 0-dichlorobenzene (25.81), m-dichlorobenzene (0.23), p-dichlorobenzene ( 38. 62), Tricyclobenzene (0.23) The value of {p ÷ (o + p) 100} calculated from the above composition was 60 (%).

Production Example 8

 (Production of 10H-phenothiazine 10-carboxylic acid (4-chlorophenyl) ester)

 (1) Manufacturing example

5.00 g (25.1 mimol) of 10 H-phenothiazine was dissolved in 50 mL of clozen benzene. The solution chloroformate 4 Ichiku B port phenyl ester _{(C l C OO CH 4 C} 1) 5. 036 g of (2 6.3 mi Rimoru) at room temperature, under reflux, and allowed to react for 1 5 hours. The reaction was followed by gas chromatography to find that unreacted 10H-phenothiazine was 9.1% and that 10H-phenothiazine-11-carboxylic acid (4-chlorophenyl) ester was 91.1. 8%.

 The yield determined by the marker method was 90.2%.

 The reaction solution was cooled to room temperature, and benzene was distilled off under reduced pressure. The crude crystals were recrystallized from ethyl acetate. Precipitated crystals are collected and dried under vacuum to obtain the desired product

6. 9 g were obtained.

 (2) Physical properties

 Pale green crystal, m.p .: 1 79—180 ° C

IR (KB r, cm— ¹ ): 1 742 (C = O), 1 32, 1 224, 756

 MS (m / e, specific strength): 353 (33, M +), 198 (100) Production Example 9

 (Production of 1 OH-phenothiazine-10-carboxylic acid (4-methylphenyl) ester)

 (1) Manufacturing example

5.00 g (25.1 mimol) of 10H-phenothiazine was dissolved in 50 mL of benzene. To this solution, 5.62 g (30.1 mimol) of chloroacetic acid 4-methylphenyl ester (C 1 COOC, H ₄ CH,) was added at room temperature, and the mixture was reacted under flowing gas for 15 hours. The reaction was followed by gas chromatography, and as a result, unreacted 10H-phenothiazine was 19.2% and 10H-phenothiazine-10-potassium rubonic acid (4-methylphenyl) ester was 80.7%. Was.

 The yield determined by the Marker-1 method was 79.3%.

 The reaction solution was cooled to room temperature, and benzene was distilled off under reduced pressure. The crude crystals were recrystallized from ethyl acetate. The precipitated crystals were collected and dried under vacuum to obtain 6.2 g of the desired product.

 (2) Physical properties

 Colorless crystals, m.p .: 166-167 ° C

 ^ NMR (CDC 1 J, c5 ppm): 2.27

_{(s, 3H, - CH 3} ), 7. 0- 7. 66 (m, 12 H) IR (KB r, cm "1): 1724 (C = 0), 1512. 1484.

 1468, 1334, 1262, 1222, 1 21 0, 1 1 92, 101 4, 760

MS (m / e, specific strength): 333 (78, M ⁺ ) 198 (100) Production Example 10 (Production of 10H-phenothiazine-10-carboxylic acid (4-methoxyphenyl) ester)

 (1) Manufacturing example

5.0 g (25.1 mimol) of 10 H-phenothiazine was dissolved in 5 O mL of benzene. To this solution was added 4-methoxychlorophenyl acid (C 1 C 00 C ₆ H ₄₀ CH ₃ ) 4.91 (26.3 mimol) at room temperature, and the mixture was allowed to react for 15 hours under reflux. I let it. As a result of tracking the reaction by gas chromatography, it was found that unreacted 10H-phenothiazine was 20.5%, and that 10H-phenothiazine 10-carboxylic acid (4-methoxyphenyl) ester was 79.3%. %Met.

 The yield determined by the marker method was 78.0%.

 The reaction solution was cooled to room temperature, and benzene was distilled off under reduced pressure. The crude crystals were recrystallized from ethyl acetate. The precipitated crystals were collected and dried under vacuum to obtain 5.8 g of the desired product.

 (2) Physical properties

 Pale green crystal, m.p .: 1 29-130 ° C

1 R (KB r, cm— ¹ ): 1 7 3 4 (C = 0), 1 5 1 0, 1 4 8 6,

1 4 6 8, 1 3 3 8, 1 2 1 8, 1 1 9 6, 1 0 3 4, 1 0 1 4, 7 6 4

MS (m / e, specific strength): 349 (85, M ⁺ ), 198 (100) Production example 1 1

 (Preparation of 2-chloro-1OH-phenothiazine-10-potassium phenylester)

 (1) Manufacturing example

5.84 g (25.1 mimol) of 2-chloro-10H-phenothiazine was dissolved in 6 mL of benzene. To this solution is added Ester (C 1 C 00 C ₆ H ₅ ) (4.11 g, 23.1 mmol) was added at room temperature, and the mixture was reacted for 16 hours under flowing gas. The reaction was followed by gas chromatography to find out that unreacted 2-chloro-10H-phenothiazine was 14.3% and 2-chloro-10H-phenothiazine-10-potassium phenyl ester was 85%. It was 7%.

 The yield determined by the marker method was 84.1%.

 The reaction solution was cooled to room temperature, and benzene was distilled off under reduced pressure. The crude crystals were recrystallized from ethyl acetate-hexane to give 6.70 g of the desired product. (2) Physical properties

 Colorless crystals, m.p .: 1 27-1 28 ° C

 lH NMR (CDC13.5ppm):

 7.10-7.70 (m, 12H)

MS (m / e, specific strength): 3 5 3 (52, M ⁺ ), 232 (100), 196 (42)

Production example 1 2

 (Nucleochloride of 1 O H-Phonothiazine 10-carboxylate)

 (A) Production of nuclear chlorinated product of 10H-phenothiazine-10-carboxylic acid phenyl ester

At room temperature, 0.47 g (2.9 mimol) of anhydrous ferric chloride and 10 H— were added to 24.6 g (2.19 mol) of chlorobenzene in a light-shielded reactor under stirring. 4.7 g (14.7 mimol) of phenothiazine- 10-potassium sulfonic acid phenyl ester were added. Then the temperature of the mixture was 50. C, gaseous chlorine is blown at the same temperature, and salting is performed over 7 hours to a chlorination degree of 0.48 (based on benzene, 1.48) based on benzene at the outlet. , 10 H-Phenothiazine 10-Phenyl ester of sulfonic acid Thus, 287 g of a reaction mixture containing the chlorinated product was obtained. The nuclear chlorinated product of 10 H-phenothiazine-1 10-carboxylic acid fuunyl ester in this mixture had 3 to 6 chlorine atoms on the phenothiazine ring and the phenyl group.

 The conditions and the retention time of the gas chromatography for nuclear chlorinated product analysis are described below.

 (Conditions for gask mouth chromatography)

 Apparatus: Gasket GC manufactured by Shimadzu Corporation GC-14B Column: Glass column outer diameter 5 mm, inner diameter 3 mm, length 2 m

 Filler: GL Science Co., Ltd.

 S i l i c o n e 0 V-17 5%

 Ch r omo s or b W AW D M C S 30-50 mesh

 Column temperature: 280 ° C

 Injection temperature: 300 ° C

 Carrier gas: Helium, 120 kPa (at 280 ° C) Detector: FID (FID condition, hydrogen 55 kPa, air 50 kPa) Retention time (min) [s + t + u (nuclear chlorine substitution) ]):

 1 1.6 [3], 15.7 [4], 17.7 [4]

 20.6 [5], 23.4 [5], 27.2 [5]

 30.1 [5], 34.8 [6], 40.4 [6]

 (B) Separation of chlorinated nuclei of 10H-phenothiazine-10-potassium phenyl phenyl ester

At 90 ° C. under reduced pressure, a fraction of chlorobenzene and chlorinated chlorobenzene nucleate was distilled off from 30 g of the mixture of the above (A). The distillation residue was dissolved in ethyl acetate, washed twice with saturated saline, and then separated. The organic layer was dried over anhydrous sodium sulfate, and ethyl acetate was distilled off to obtain crystals. Acetate this crystal After dissolving in nitrile, fractionation and fractionation with an ODS column, recrystallization from acetonitrile gave the following chlorinated nuclei.

 For some of these chlorinated nuclei, high performance liquid chromatography

The retention time and physicochemical properties of (HPLC) are described below.

 (Condition of HPLC)

 Apparatus: High-performance liquid chromatograph L-620, manufactured by Hitachi, Ltd. Column: Shodex ODSpac F-411A

 4.60 x 15 O mm

E luent ： CH, CN / H ₂ 0 (7 0/30)

 F l o w r a t e: 1.0 m L / τα in

 D e c t e c t or: U V-2 6 8 n m

 Temperature: 30 ° C

 Retention time (min) [s + t + u (number of nuclear-substituted chlorine)]:

 11.8 [3], 17.5 [4], 18.9 [4]

 26.1 [5], 28.9 [5], 40.8 [6]

 ① Retention time 1 1.8 minutes:

 2, 8-dichloro-1-H-phenothiazine 10-carboxylic acid

(4-chlorophenyl) ester

 Colorless crystals, m.p .: 2 13-2 14 ° C

 JH NMR (C D C 1 J, δ p p m):

 7.37 (d, 8.54), 7.154 (d, 8.54), 7.64 (d, 2.44), 7.38 (dd, 2.4 4.7.994), 7.334 (d, 7.94)

 M S (m / e specific strength): 4 2 3 (1 8, M +), 2 6 6 (1 0 0), 2 3 1 (8), 1 96 (1 4)

② Retention time 17.5 minutes: 2,3,8—Trichloro 10 10 H—Phenothiazine 10—Cyrurubonic acid (4-chlorophenyl) ester

 Colorless crystals, m.p .: 218-219 ° C

 1 H NMR (C D C 1 J, 6 p p m)

 7.36 9 (d, 8.54), 7.140 (d, 8.54),

7. 6 2 8 (d, 2.44), 7.24 5 (d d, 1.22,

8.55), 7.32 8 (d, 8.55), 7.49 1 (s), 7.73 3 (s)

 M S (mZe specific strength): 4 5 7 (18, M +), 3 0 1 (1 0 0), 2 6 5 (9), 2 3 0 (2 1), 1 9 5 (6)

③ Retention time 1 8.9 minutes:

 2. 4, 8 — Trichloro 10 H — phenothiazine 10 — Ca-Rubonic Acid

 Colorless crystals, m.p .: 179-180 C

_{1 H NMR (CDC 1 3,} δ ρ ρ m)

 7.36 (d, 8.54) .7.13 2 (d, 8.54), 7.54 4 (d, 1.83), 7.260 (dd, 1. 8 3,

8.54), 7.37 7 (d, 854).

 7. 3 7 2 (d, 1.83), 7 63 (d. 1.83) MS (mZe specific intensity) 4 5 7 (2 6, M +), 3 0 1 (1 0 0) .

 2 6 5 (1 0), 2 3 0 (2 0), 1 9 5 (4)

④Retention time 26.1 minutes:

 Tetralolor 10 H—Phonothiazine 10 —Caprolubonic acid (4—Chlorophenyl) ester [mixture]

 Colorless crystals, m.p 198-200 ° C

MS (mZ e specific strength): 491 (26, M ⁺ ) 33 36 (100), 300 (8), 265 (20), 230 (3), 194 (5)

⑤Retention time 28.9 minutes:

 2,4,7,8-Tetrachloro- 10H-Phenothiazine 10-potency Rubonic acid (4-chloro phenyl) ester

 Colorless crystals, m.p .: 238-240. C

_{lH NMR (CDC 1 3, δ} ppm:

 7.363 (d, 8.55), 7.125 (d, 8.55),

7.534 (d, 1.84), 7.383 (d, 1.84),

7.543 (s), 7.726 (s)

MS (mZe specific strength): 49 1 (24, M ⁺ ), 336 (100),

301 (8), 264 (20), 230 (2), 194 (3)

⑥Retention time 40.8 min:

 2,3,4,7,8-pentanochloro-1 OH-phenothiazine-1 10-carboxylic acid (4-chlorophenyl) ester

 Colorless crystals

 Η NMR (CDC1δppm):

7.368 (d, 9.16), 7.122 (d, 9.16), 7.667 (s), 7.548 (s), 7.726 (s) MS (mZe specific strength): 525 (24, Μ ⁺ ), 370 (100), 335 (10), 298 (21), 264 (2), 230 (3), 1 56 (4), 11 1 (96)

Production example 1 3

 (1 OH—Phenothiazine 110 nuclei chloride of phenyl phenyl rubinate)

(A) Production and separation of 10H-phenothiazine 0-nuclear chlorinated phenyl ribonate 180 mg (1.11 mmol) of anhydrous ferric chloride and 10 H-phenothiazine—10-potassium funalyl ester (using the product prepared in Reference Production Example 1) 531 mg (1.67 mmol) To the mixture was added 450 g (5.76 mol) of benzene. Chlorine was introduced at a rate of 3.0 m 01 / h while maintaining the temperature at 60 ° C., and the reaction was carried out for 3.5 hours. Then, benzene and a benzene chlorinated benzene fraction were distilled off from the chlorination reaction solution at 90 under reduced pressure.

 The distillation residue was dissolved in ethyl acetate, washed twice with saturated saline, and then separated. The organic layer was dried over anhydrous sodium sulfate, and ethyl acetate was distilled off under reduced pressure using a rotary evaporator to obtain a crystalline product. The crystal was dissolved in acetonitrile, fractionated by ODS column chromatography and silica column chromatography, and recrystallized from acetonitrile to obtain the following nucleated chloride.

 The nuclei chloride of 10H-phenothiazine 110-carboxylic acid phenyl ester had 3 to 6 chlorine atoms on the funothiazine ring and the phenyl group.

 (B) For some of these chlorinated nuclei, the retention time and physicochemical properties of high performance liquid chromatography are described below.

 (Condition of HPLC)

 Covert: High performance liquid chromatograph L-6200 manufactured by Hitachi, Ltd. Column: Shodex ODSpak F-411 A 4.6 øx

 1 50mm

E 1 uent: CH ₃ CN / H ₂ 0 (70 30)

 F ow r a t e: 1.0m / ^ i n

 D e c t e c t o r: UV- 268 nm

Temperature: 30 ° C Retention time (min) [s + t + u (number of nuclear-substituted chlorine)]:

 1 7.0 [4], 24. 9 [5], 27.4 [5]

①Retention time 17.0 minutes:

 1,2,8-Trichloro-10H-Phenothiazine-10-potassium ribonate (4-chlorophenyl) ester

 Colorless crystals, m.p .: 148-149 ° C

 MS (mZe specific strength): 457 (20, M +), 302 (100),

 265 (9), 230 (22), 194 (6)

Confirmation of the bonding position of chlorine including the 1-position of the phenothiazine ring was performed by —ΝR and ¹³ C—NMR.

 ② Retention time 24.9 minutes:

 1,2,7,8-Tetrachloro 10H-Phenothiazine 10-force Rubonic acid (4-chlorophenyl) ester

Colorless crystal, mp: 197-198 ^e C

MS (mZe specific strength): 491 (12, M ⁺ ), 336 (100), 301 (9), 264 (20), 229 (2), 194 (4) Bonding position of chlorine including 1-position of phenothiazine ring Checking was carried out in ^{1 Η- Ν Μ} R and ¹³ C-NMR.

 ③ Retention time 27.4 minutes:

 Tetrachloro 10Η-phenothiazine-10-carboxylic acid (4-chlorophenyl) ester (mixture)

 Colorless crystals, m.p .: 154-156 ° C

 MS (mZe specific strength): 491 (12, M +), 336 (100), 301 (6), 264 (20), 228 (2), 194 (4) Production example 14

(Nuclear salinization of toluene) (A) Preparation of catalyst

 150 g of benzene was added to 60 mg of anhydrous ferric chloride and 177 mg of 10H-phenothiazine-lO-carboxylate (used in Reference Production Example 1). While maintaining the temperature at 60 ° C., chlorine was introduced at a rate of 1.0 mO I Zh, and the reaction was carried out for 3.5 hours. Then under reduced pressure, 90. At C, benzene and benzene chlorinated benzene fractions were distilled off from the chlorination reaction solution. Using the distillation residue as a catalyst, a nuclear chlorination reaction of toluene shown in (B) below was performed. The above distillation residue contained a nuclear chlorinated product of phenyl ester of 10H-phenothiazine-110-potassium ribonate in (1) to (3) shown in Production Example 13 (B).

 (B) Nuclear chlorination reaction

 To the catalyst prepared in the above (A), 184.3 g (2.00 mol) of toluene was added, and while maintaining the temperature at 30 ° C, chlorine was introduced at a ratio of 1.Omo 1 Zh. At the end of the 2 hour reaction, the mixture was analyzed by gas chromatography to obtain a reaction mixture having the following mass composition (%).

 Toluene (2.77), orthochlorotoluene (44.10), parachlorotoluene (52.59), dichlorotoluene (0.54) The value of {p ÷ (o + p) XI 00} calculated from the above composition Was 54.4%.

Production Example 15

 (Nucleation chlorination reaction of ethylbenzene)

 To the catalyst prepared in the same manner as in Production Example 14 (A), 106.2 g (1.00 mol) of ethylbenzene was added, and chlorine was introduced at a rate of 0.5 m 0 1 Zh while maintaining the temperature at 30 ° C. . At the end of the 2 hour reaction, the mixture was analyzed by gas chromatography to obtain a reaction mixture having the following composition by weight (%).

Ethylbenzene (6.05), onolesok (35.60), parachloroethylbenzene (58.35)

 The value of {p ÷ (o + p) × 100} calculated from the above composition was 62.1%.

Production Example 16

 (Nuclear chlorination of para-xylene)

 106 g (1 mol) of paraxylene was added to the catalyst prepared in the same manner as in Production Example 14 (A) above, and chlorine was introduced at a rate of 0.75 mo I Zh while maintaining the temperature at 50 ° C. . At the end of the 2-hour reaction, the reaction product was analyzed, and it was confirmed that the product had the following weight composition (%).

Para-xylene (0.03), 2-cyclopara-xylene (58.34), 2.5-dichloropara-xylene (35.95), 2,3-dichlorono, ^0- xylene (5.5.56), tri-clo Para-xylene (0.12) Calculated from the above composition {(2,5-dichloro-substituted) ÷ ((2,3-dichloro-substituted) + (2,5-dichloro-substituted)) X 100 } Value was 86.6%.

Reference Production Example 1

 (Production of 10H-phenothiazine- 10-potassium phenyl phenyl ester)

 (1) Manufacturing example

5.00 g (25.1 mimol) of 10H-phenothiazine was dissolved in 5 OmL of benzene. To this solution, 4.125 g (26.3 mimol) of chloroformic acid phenyl ester (C 1 COOCgH _c ) was added at room temperature, and the mixture was reacted under reflux for 11 hours. As a result of tracking the reaction by gas chromatography, unreacted 10H-phenothiazine was found to be 2.02% and 10H-phenothiazine-lO-carboxylate phenyl ester was found to be 97.98%.

- twenty one - The yield determined by the Marker method was 97.44%.

 The reaction solution was cooled to room temperature, and benzene was distilled off under reduced pressure. The crude crystals were recrystallized from ethyl acetate. The precipitated crystals were collected and dried under vacuum to obtain 7.21 g of the desired product.

 (2) Physical properties

 Colorless crystals, m.p. 165-166 ° C

_{! H NMR (CDC 1 3,} <5 pm):

 7. 0-7. 56 (m, 13 H)

IR (KB r, cm— ¹ ): 3120, 3080, 1 730 (C = 0),

1592, 1502, 1484. 1484, 1468,

1448, 1334, 1312. 1218, 764, 750,

688

 MS (m / e, specific strength): 319 (69, M +), 1 98 (100), 155 (20)

Reference Production Example 2

 (Manufacture of 10-benzoyl—10-phenothiazine)

 (1) Manufacturing example

 At room temperature, 10Η-phenothiazine (5.08 g, 25.5 mmol), anhydrous sodium carbonate (10.03 g, 94.6 mmol), and dioxane (50 g) were charged to the reactor at room temperature. Heated to ° C. A mixed solution consisting of 10.74 g (76.4 mimol) of benzoyl chloride and 50 g of dioxane was added dropwise at 30 ° C over 10 minutes. Next, the temperature was raised to 90 ° C., and the reaction was performed for 3.5 hours.

After cooling the reaction solution to room temperature, it was poured into a dilute hydrochloric acid composed of 30 mL of hydrochloric acid and 50 OmL of water. Then, 200 mL of benzene was added and extracted. The benzene layer was washed with water (80 mL x 3 times), washed with 100 mL of aqueous sodium bicarbonate, and then washed with water. Was.

 The benzene layer was dried over anhydrous sodium sulfate, and benzene was distilled off under reduced pressure to obtain a crude crystal. The crude crystals were recrystallized from benzene to give 6.68 g of needles.

 (2) Physical properties

 Colorless needles, m.p .: 173-174 ° C

IR (KB r, cm " ¹ ): 3092, 3072, 1 674 (C = 0), 1480, 1464, 1448, 1326, 1326, 1262, 766, 752, 732, 706, 690

MS (m / e, specific strength): 303 (42, ⁺ ), 198 (82),

105 (100)

 [Industrial applicability]

 The combined use of the 10H-phenothiazine-phenylene phenylesters of the present invention and Lewis acids is useful as a catalyst for regioselective nuclear chlorination of aromatic hydrocarbons. Furthermore, the catalyst for regioselective nuclear chlorination by this combination has the feature that the regioselectivity does not decrease even if the nuclei chlorination is carried out at a reaction temperature exceeding 45 ° C. This has the advantage of improving selectivity.

Claims

The scope of the claims 1) A catalyst for selective nuclear chlorination of S-position of aromatic hydrocarbons, comprising a 10H-phenothiazine-1 10-fluorocarboxylic acid phenyl ester represented by the following formula (I) and a Lewis acid. (C I) t

(In the formula, represents a halogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a nitro group or a cyano group, n represents an integer of 0 to 5, and when n is greater than 2, Xs may be the same or different;  s represents an integer of 0 to 5, t represents an integer of 0 to 4, u represents an integer of 0 to 4, and (n + s) is 5 or less. )  2) 10 H-phenothiazine-10-carboxylic acid phenyl ester is such that n in the formula (I) represents an integer of 0 or 1, s represents an integer of 0 to 2, and t and u forces are each 0. A compound wherein X represents a halogen atom, a methyl group or a methoxy group, and the Lewis acid is at least selected from the group consisting of ferric chloride, aluminum chloride and antimony trichloride. 2. The catalyst for regioselective nucleation of aromatic hydrocarbons according to claim 1, which is one kind. 3) 10H-phenothiazine- 10-potassium phenyl phenyl esters represented by the following formula (I).

(In the formula, X represents a halogen atom, an alkyl group having 14 carbon atoms, an alkoxy group having 14 carbon atoms, a nitro group or a cyano group, η represents an integer of 0 and 5, when η is greater than 2, a plurality of Xs may be the same or different; s represents an integer of 05, t represents an integer of 04, u represents an integer of 04, and (n + s) is 5 or less. However, n = s = t = u = 0 is excluded. )  4) As a catalyst, an aromatic hydrocarbon characterized by chlorinating an aromatic hydrocarbon by using a 10H-phenothiazine-10-potassium phenyl sulfonic acid ester represented by the following formula (I) in combination with a Lewis acid: Regioselective nuclear chlorination of hydrocarbons.

(In the formula, X represents a halogen atom, an alkyl group having 14 carbon atoms, an alkoxy group having 14 carbon atoms, a nitro group or a cyano group, n represents an integer of 0 and 5, when n is greater than 2, X may be the same or different; s represents an integer of 0 5, t represents an integer of 04, u represents 0 4 Where (n + s) is 5 or less. )  5) 10H-phenothiazine-10-carboxylic acid phenyl ester is represented by the formula (I) wherein n is an integer of 0 or 1, s is an integer of 0 to 2, and t and u are each 0 to 3 A compound showing an integer and X represents a halogen atom, a methyl group or a methoxy group, and the Lewis acid is at least one selected from the group consisting of ferric chloride, aluminum chloride and antimony trichloride 5. The method for regioselective nuclear hydrogenation of aromatic hydrocarbons according to claim 4.  6) The aromatic hydrocarbon is selected from the group consisting of benzene, toluene, 0-xylene, p-xylene, black benzene, black toluene, 0-dichlorobenzene and 1-chloro-2,5-dimethylbenzene. 5. The method for regioselective nuclear chlorination of aromatic hydrocarbons according to claim 4, wherein the method is at least one kind.  7) The method for regioselective nuclear chlorination of aromatic hydrocarbons according to claim 4, wherein the reaction temperature is 45 to 75 ° C.