JP3017005B2 - Synthesis of deactivated anilines - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to the synthesis of deactivated anilines. In particular, the present invention relates to a method comprising a dialkylamination step with an amide.

[0002]

BACKGROUND OF THE INVENTION The synthesis of aniline is generally carried out with nitro derivatives, which consist of hydrogenating them. However, this method is subject to many limitations and is not always easy to apply when the product is sensitive to hydrocracking or produces many side reactions. In addition, the location of the nitro function is not always easy, and certain syntheses require a large number of steps.

[0003]

Accordingly, the present invention relates to a novel synthetic method which can be used, in particular, for the preparation of anilines substituted in the p-position by an electron-withdrawing group (EAG).

[0004]

The above object is achieved by the following formula (I).

Embedded image (Wherein, R ₁ represents the anion (R ₁ ^- groups as constituting a) is good leaving groups, i.e. selected from among bromine or chlorine atom, preferably Ri Oh chlorine atom, R ₂ is hydrogen , Halogen and the following formula: R- (CX ₂ ) n- (III) (where R is halogen and X is each halogen
Wherein n is at least 1) , R ₃ is selected from hydrogen and halogen, R ₄ is hydrogen, halogen and the following formula: R- (CX ₂ ) n- (III) (where R is halogen and X is each halogen
Wherein n is at least 1) , R ₅ is selected from hydrogen and halogen, R ₆ is hydrogen, halogen and the following formula: R- (CX ₂ ) n- (III) (where R is halogen and X is each halogen
In it, n represents selected from among perhaloalkyl group at least at a). Provided that the groups R ₂ , R ₆ and R ₄
At least one of which is assumed to be electron-withdrawing by an inducing effect) in the presence of a base in the range of 150 to 3
It is achieved by a process involving a step consisting of reacting with a dialkylamide at a temperature of 00 ° C., preferably 180-250 ° C. (unless otherwise stated herein, the position zero is not critical).

[0005]

DETAILED DESCRIPTION One of the surprising features of the present invention is that less than two nitro groups are present on the same ring, and the reaction proceeds even in the absence of such groups. It comes from the fact that the conditions could be found. Advantageously, as a result of their nature or as a result of the arrangement of electron-withdrawing groups, the anion (R ₁ ⁻ ) constitutes a better leaving group than the anion resulting from the groups R _{2 to} R ₆ .

[0006] Advantageously, the electron-withdrawing group (EAG) is
Light weight halogen (fluorine, chlorine, bromine), most often chlorine and preferably perhaloalkyl, more preferably trihalomethyl, preferably selected from among perfluoroalkyl group. Radicals R ₃ and R ₅ are preferably not so disturbing, preferably water Motomata with the proviso that they are not good leaving groups as R ₁ is halogen, preferably a fluorine or chlorine.

[0007] The pair Ruharoarukiru the following formula R- (CX _{2) n} - with (III) (wherein, n represents at least 1 in rather equal, X is halogen, respectively, is preferably selected from among fluorine and chlorine , R
There the Ha androgenic, groups of preferably chlorine or fluorine)
U. X is the same in most cases. n is generally at most equal to 10, and in particular perfluoroalkyl is o-
When it is in the position, it is 6 or less, preferably 4 or less.

The solvent can be any solvent that does not decompose under the experimental conditions and is inert to the reactants, and is advantageously polar (ie, its dielectric constant ε is at least equal to 30). . When the solvent is protic, and furthermore when the solvent is not, the solvent advantageously has a pK of water.
has a pKa at least equal to a, ie 14.
Solvent is to be understood as meaning any mixture that can be used as a solvent and also any pure substance. However, it is preferred to work using either excess reactants or excess substrate as the sole solvent.

Among the bases that can be used, anionic bases, including carbonates, are preferred. The bases used are advantageously alkali metal oxides, alkali metal amides, alkali metal hydroxides and alkali metal alcoholates.

For good results, it is desirable for the pKa of the conjugate acid of the base to be at least equal to 9, advantageously equal to 10, preferably equal to 12.

In the reaction system, especially when copper is used as a catalyst, use of a hydroxylated derivative, particularly water, as a solvent is acceptable. Thus, the reaction is advantageously performed in the presence of copper. Copper is preferably introduced in the form of a cuprous salt and in an amount of 0.1 mol% to 10 mol% relative to the substrate. Advantageously, the amounts of reactants and catalyst used, assuming the amount of substrate is 1, are as follows: Base: 0.5-5 gram equivalent, preferably 2-4 gram equivalent Amide: 1-100 gram equivalent, preferably 5-25
Gram equivalent

The amide is preferably a dialkyl amide of a light carboxylic acid (10 or fewer carbon atoms). It is possible to use diamides such as tetramethylurea,
Tetramethylguanidine can also be used. The best result is that the dialkyl amide is a dialkyl formamide and the alkyl group grafted on the nitrogen of the amide is as light as not more than 6, preferably less than 4, and preferably not more than 3, carbon atoms. Obtained when something is. Methyl derivatives are the preferred derivatives.

The reaction is carried out in an autoclave under experimental conditions and under the natural pressure of the reactants. Although not essential, it is preferably carried out under an inert atmosphere, for example, under a nitrogen or argon atmosphere.

The invention is of particular importance for obtaining trifluoromethyl derivatives. In fact, contrary to all expectations, perfluoroalkyl groups, especially trifluoromethyl groups, are stable under the operating conditions of the present invention. According to the invention, it has thus been possible to synthesize p-trifluoromethyl-N, N-dimethylaniline in a single step from the corresponding halogenated derivative, in particular the chlorinated derivative. The results show that the starting material is a perfluoroalkyl function, which is an electron-withdrawing group, generally the m- and p- of the trifluoromethyl group.
A dihalogenated or trihalogenated derivative at the -position,
Preferably, it is a dichloro or trichloro derivative.

In other words, of particular importance is that in formula (I), R ₁ is chlorine or bromine, preferably chlorine;
₂ is fluorine, chlorine or bromine, preferably chlorine, R ₃
Is hydrogen, fluorine, chlorine or bromine, preferably chlorine;
In the synthesis where R ₄ is perfluoroalkyl, generally trifluoromethyl. However, all the compounds obtained by this step of the present invention cannot be used directly. The first or second aniline can be said to be more useful than the corresponding tertiary aniline.

By the way, a common method for demethylating anilines involves the use of hydrobromic acid (HBr), which adds a functional group desired to be present on the ring with the aniline functional group. Danger of destruction. Functional groups which have been shown to be unstable include halogenated functional groups, most often benzylic, i.e. perhalogenated at the alpha position relative to the aromatic ring, especially perfluoroalkyl groups, most often In the case of, a trifluoromethyl group can be mentioned.

For this reason, one of the objects of the present invention is to provide anilines, especially anilines which have been deactivated, that is to say that the acid associated therewith has a pKa at most equal to 2, preferably equal to 1. The object is to provide a method for dealkylating things. Another object of the present invention is to provide an unstable functional group as described above, for example, a perfluoroalkyl group,
It is an object of the invention to provide a method of the above type which does not generally impair the trifluoromethyl function. It is yet another object of the present invention to provide a method of the above type that does not affect the substituent at the m-position with respect to aniline.

These and other objects which will become apparent from the following description are advantageously achieved by a process for N-dealkylating a deactivated mono- or di-alkylated aniline, which comprises the following steps: Step: b) Including a halogenation known per se with a halogenating agent of the free radical type. The halogenation under conditions which are known to involve a free radical, is preferably carried out by starting the reaction (electromagnetic radiation of the appropriate wavelength, using their equivalents and peroxide or it).

These anilines are advantageously of the formula (I)
I)

Embedded image (Where R ₁ represents a mono or dialkylamino group, R ₂ is selected from hydrogen, halogen and perhaloalkyl groups, and R ₃ is hydrogen, pseudohalogen and halo
Selected from among plasminogen, R ₄ is hydrogen, halogen and perfluoroalkyl
Selected from among the haloalkyl group, R ₅ is hydrogen, Pusoi
Selected from among Doharogen and halogen, R ₆ has hydrogen, a chosen) from among the halogen and perhaloalkyl group.

In the first step, if there are free sites, the o- and p-positions are halogenated by a halogenating agent. In the second step, if the amount of halogenating agent used is limited to a stoichiometric amount (or about 10% excess with respect to the stoichiometric amount for a single dealkylation), the alkyl group If, also, the amount of halogenating agent is not limited, both alkyl groups are monohalogenated in the α-position and can be isolated and have the following structure Ar-N (- _{CH 2-x Z x -R 1} ') (- CH 2-y Z y -R 2') (III ') ( wherein, Z represents a halogen brought by halogenating agent, R _1' is An alkyl group having at most 4 carbon atoms, preferably hydrogen, R ₂ ′ is an alkyl group having at most 4 carbon atoms, preferably hydrogen, and R ₁ ′ and R ₂ ′ are nitrogen Which can be combined to provide a unique group with which to form a ring). Compounds of this type are described further in the description.

This dealkylation is particularly surprising in its selectivity. Because the m-position is unaffected and the carbon of the alkyl chain in the α-position relative to the aniline function is not substantially affected more than once, thereby saving expensive reactants and reducing the amount of effluent. It is because it reduces. Furthermore, it is also possible to carry out the selective mono-dealkylation of anilines in a broad sense.

During the work of the present invention, this halogenation is carried out on the carbon of the alkyl chain directly attached to the aniline function and on the o- and p-positions (if they are free) with respect to the aniline function. Only found to happen.

Generally, this halogenation step is carried out in a chlorinated or simply polar solvent at a temperature of from 0 to 100 ° C, preferably from about 0 to 50 ° C. When a solvent having a boiling point of less than 100 ° C. is used, it is convenient to carry out the reaction under reflux and, if appropriate, under reduced pressure so as to bring the reflux temperature into the preferred range.

In general, the process comprises the following steps: c) the hydrolysis of the product of the halogenation step b). The hydrolysis is known per se and preferably takes place in the presence of an absorbent of the released acid.

In the halogenation, various halogens selected from chlorine, bromine and iodine can be introduced into the molecule. Generally, chlorine is preferred for economic reasons. However, if you want to bring a specific halogen to the ring,
It is appropriate to use a halogenating agent that provides this halogen. The same is true if one wishes to avoid free o- and p-perhalogenation with respect to aniline. In this case, halogenation with a halogenating agent which introduces a higher rank halogen than the halogen present in the ring is preferred, and then dehydrohalogenation is carried out by means known per se to be selective. .

Examples of solvents for this halogenation include solvents which are inert under the experimental conditions, such as, for example, compounds such as carbon tetrachloride, chlorobenzene, dichlorobenzene and acetonitrile. Can be. In most cases, the halogenating agent is a molecular or elemental halogen. Apart from the halogen itself, thionyl halide or sulfuryl SO _n Cl ₂ (n is 1
Or 2), phosphorus pentachloride PCl ₅ , PCl ₃ / C
l ₂ mixtures, alkyl hypochlorite and compounds of the type X ₂ O (X represents a halogen other than fluorine and iodine).

When these reactants are not, of course, free radical reactants (such as thionyl halides or sulfuryls), they react in the presence of substances or conditions which promote the formation of free radicals, especially Hal. It is used under the action of actinic radiation, which is known to promote the formation of radicals. It is possible to choose between monodealkylation or dialkylation between ring halogenations by the choice of stoichiometric amounts. In the case of bromine, when it is stable and not very toxic, a compound corresponding to the above-mentioned chlorine compound and N-bromosuccinimide (NB
And S) type compounds. In the case of iodine, the best iodinating agent is molecular iodine.

Thus, the derivatives obtained from 1,2-dichloro-4-trifluoromethylbenzene or p-trifluoromethylchlorobenzene can be converted to 4-trifluoromethyl-2-chloro-6 by halogenation known per se.
-Converted to haloaniline, then hydrolyzed. Although it was not expected, the formula _{Ar-N (-CH 2-x} Cl x -R 1 ') (- CH 2-y Cl y -R 2') (III) ( wherein, x and y Has a value of 0 or 1, respectively, and x
+ Y is greater than 0 and Ar represents a group derived from formula (I) by removing the group R ₁ to leave a free valency and optionally by chlorination at the free o- and m-position. The intermediate products of) are stable enough to be isolated and constitute precursors to many chemical derivatives. Furthermore, their isolation from the reaction medium makes it possible to obtain a high purity of the fully or partially dealkylated anilines, and compounds in which y = 1 and x = 1 are very predominant. Therefore, the separation is very easy. The method of the present invention works well, in particular, its pK is preferably at most equal to 2, advantageously equal to 1, preferably equal to 0.
This is true for mono- or dialkylated anilines (in a broad sense) having a.

It has also been found during the study of the present invention that it is possible according to the invention to selectively dealkylate mono- and dialkylanilines without affecting the original aromatic group. The process comprises the following steps: b ') the aniline and ammonia or an amine, which is preferably a secondary amine, often free or in the form of its salt, in a catalytic amount of a pyridine salt, preferably Using a method which comprises reacting in the presence of a hydrohalide. This surprising reaction has the advantage that it can be selective for dialkylanilines and even when the alkylanilines are secondary.

Here, the term "aniline" should be understood in its broadest sense. That is, it refers to any amine directly attached to an electron deficient aromatic ring system (preferably only one). This electron deficiency is measured by the pKa of the acid associated with the aniline function desired to be dealkylated. Thus, aniline includes not only aniline itself, but also compounds obtained by substitution of aniline, including aniline bonded to other ring systems such as naphthylamine. The lack of electrons in the ring system can be any known cause, for example,
Presence of any kind of electron-withdrawing substituent or ring (6-membered ring)
Probably because of the presence of a complex atom in Also, it should be understood that amines are meant to include mixtures of the amines described above. The amine may be pyridine. Pyridine is to be understood in its broadest sense, ie, any molecule having a pyridine ring in which the nitrogen atom has no substituent. Thus, pyridine should be understood to include not only pyridine itself, but also compounds resulting from the substitution of pyridine, including pyridine bonded to other ring systems such as, for example, quinoline. It is preferred that the substituents on pyridine itself have a boiling point at most equal to about 200 ° C. It should also be understood that pyridine includes mixtures of pyridine as described above.

If it is desired to demethylate dimethylaniline, it is also possible to carry out mono- or di-dealkylation. Mono-dealkylation is present when the acid corresponding to the pyridine and / or amine salt is a relatively weak acid, that is, when its pKa is at most equal to 1, and preferably equal to 3. Generally, pyridine hydrochloride is used alone or in the presence of an amine hydrochloride. Advantageously, the amine has a pKa greater than that of pyridine, preferably at least 2 units, more preferably 2.5 units.

Advantageously, step b ') comprises from 150 to 220
C., preferably at a temperature of 180 to 220C. Excess amine, preferably 1 to 50 equivalents, preferably 2
Suitably, it is carried out using an excess of pyridine hydrochloride of from 10 to 10 equivalents (with respect to the stoichiometric amount of demethylation).

One of the most surprising and most beneficial aspects of this technology is that aniline has a perfluoroalkyl functionality,
In general, no ammonolysis is observed even with a trifluoromethyl group. The pKa of the acid associated with aniline is at most equal to 5 and 2 for release,
Preferably the reaction is easier when equal to zero.

[0034]

The following examples are illustrative of the invention and do not limit it in any way.

Examples 1-4 Reactions:

Embedded image p-chlorotrifluoromethylbenzene (1.29 g,
7.15 mmol), DMF (4 g) and sodium amide (0.56 g, 14.3 mmol) are introduced in this order into a jacketed Teflon autoclave (100 ml). The autoclave is sealed and the mixture is heated to 180 ° C. with stirring for 24 hours. After treating the reaction medium, p-trifluoromethyl-N, N-dimethylaniline was obtained (74% DC, 77% TY). Influence of solvent ・ Reaction

Embedded image (Where, X = Br or preferably Cl) · _{Conditions: CF 3 -Φ-Cl 0.322g (} 1.79 mmol) NaNH ₂ 0.14 g (53.6 mmol) DMF 4g jacketed teflon product autoclave (100m
l) The results obtained are shown in Table 1 below.

[Table 1] Temperature range: 150-230 ° C using DMF

Examples 5 to 9

Embedded image In a 1 liter Hastelloy autoclave, 3,4-dichlorotrifluoromethylbenzene (47.1 g, 0.1 mL) was added.
212 mol), DMF (200 g) and sodium hydride pellets (25.8 g, 0.645 mol). Close the autoclave and stir the mixture for 2 hours.
Heat to 10 ° C. for 3 hours. The pressure reaches 9 bar. After treating the reaction medium, 4-trifluoromethyl-2-chloro-N, N-dimethylaniline was obtained (DC92).
%, CY93%). The results obtained are shown in Table 2 below.

[Table 2]

EXAMPLE 10 Sulfuryl chloride (9.10 g) was prepared by dissolving 2-chloro-4-trifluoromethyl-N, N-dimethylaniline (14.25 g, 63.8 mmol) in carbon tetrachloride (90 ml). (5 g, 70 mmol). The experiment was performed in the presence of a strong lamp and in the absence of light. 2 at 70 ° C
After heating for an hour, the solution is treated with an excess of 50% aqueous sodium hydroxide. The results of the HPLC analysis of the organic phase are shown in Table 3 below.

[Table 3]

Example 11 2,6-Dichloro-4-trifluoromethyl-N, N-
Dissolve a mixture of dimethylaniline (4.5 g, 17.4 mmol) and 2,6-dichloro-4-trifluoromethyl-N-methylaniline (1.88 g, 6.9 mmol) in carbon tetrachloride (60 ml) The resulting solution is treated with sulfuryl chloride (5.7 g, 42.2 mmol). The reaction mixture is cooled to 10 ° C. and irradiated with a UV lamp for 6 hours, then treated with excess 50% aqueous sodium hydroxide solution. HPLC analysis of the organic phase indicated the presence of 2,6-dichloro-4-trifluoromethylaniline (70 mol%).

Example 12 A solution of 2,6-dichloro-4-trifluoromethyl-N-methylaniline (1.31 g, 5.4 mmol) in carbon tetrachloride (40 ml) was treated with sulfuryl chloride (4. (5 g, 33 mmol). The reaction mixture is cooled to 10 ° C., irradiated with a lamp for 1 hour and then treated with an excess of 50% aqueous sodium hydroxide solution. HPLC analysis of the organic phase indicated the presence of 2,6-dichloro-4-trifluoromethylaniline (83 mol%).

Example 13 2,6-Dichloro-4-trifluoromethyl-N, N-
A stoichiometric amount of gaseous chlorine is introduced into a solution of dimethylaniline (3 g, 11.6 mmol) in carbon tetrachloride (60 ml). During the introduction of chlorine, the reaction mixture is cooled to 10 ° C. and irradiated with a UV lamp. HPLC analysis of the organic phase after treatment showed a 92% conversion and 6 hours after 1 hour.
A yield of 4% 2,6-dichloro-4-trifluoromethylaniline was shown.

Example 14 2,6-Dichloro-4-trifluoromethyl-N, N-
A stoichiometric amount of gaseous chlorine is introduced into a solution of dimethylaniline (2.25 g, 8.7 mmol) in 1,2-dichlorobenzene (65 ml). During the introduction of chlorine,
The reaction mixture is cooled to 10 ° C. and irradiated with a UV lamp. HPLC analysis of the organic phase after treatment showed 99% conversion and 92% yield of 2,6-dichloro-4-trifluoromethylaniline after 50 minutes.

Example 15 2,6-Dichloro-4-trifluoromethyldimethylaniline (8.45 mmol) was dissolved in 1,2-dichlorobenzene (65 ml) and cooled to 10 ° C. to give a theoretical amount. Of gaseous chlorine. 15 with UV lamp
After irradiating the reaction medium for minutes, the reaction is continued for 2 hours with the light blocked. HPLC analysis of the organic phase after treatment showed 98%
And the yield of 34% 2,6-dichloro-4-trifluoromethylaniline.

Example 16 1,2,3-Trichlorobenzene (0.963 g), D
MF (4 g) and sodium hydroxide (0.4 g) were added in that order to a jacketed Teflon autoclave (100 g).
ml). The autoclave is sealed and the mixture is heated with stirring to 220 ° C. for 24 hours. Conversion is 7
8%. After treating the reaction medium, 0.517 g of a mixture of dichloro-N, N-dimethylaniline is contacted with pyridine hydrochloride (5.70 g). Mix 185
Heat to 45 ° C for 45 minutes. HPLC analysis of the mixture revealed 2,
It indicated the presence of 3-dichloroaniline (95%) and 2,6-dichloroaniline (5%).

Example 17 1,2,4-Trichlorobenzene (0.766 g), D
MF (4 g) and sodium hydroxide (0.4 g) were added in that order to a jacketed Teflon autoclave (100 g).
ml). The autoclave is sealed and the mixture is heated with stirring to 220 ° C. for 24 hours. Conversion is 8
2%. After treating the reaction medium, 0.223 g of a mixture of chloro-N, N-dimethylaniline is contacted with pyridine hydrochloride (3.2 g). Heat the mixture to 185 ° C. for 60 minutes. HPLC analysis of the mixture showed 2,4-
It indicated the presence of dichloroaniline (96%) and 3,4-dichloroaniline (4%).

Example 18 1,2,4,5-tetrachlorobenzene (0.919
g), DMF (4 g) and sodium hydroxide (0.4 g).
g) in that order into a jacketed Teflon autoclave (100 ml). The autoclave is sealed and the mixture is heated with stirring to 220 ° C. for 24 hours. The conversion was 100%. After treating the reaction medium, 0.50 g of a mixture of trichloro-N, N-dimethylaniline is contacted with pyridine hydrochloride (5.8 g). Heat the mixture to 190 ° C. for 60 minutes. HPLC analysis indicated the presence of 2,4,5-trichloroaniline (100%).

Example 19 2,6-Dichlorobromobenzene (0.992 g), D
MF (4 g) and sodium hydroxide (0.4 g) were added in that order to a jacketed Teflon autoclave (10 g).
0 ml). The autoclave is sealed and the mixture is heated with stirring to 220 ° C. for 24 hours. The conversion was 89%. After treating the reaction medium, chlor-N,
0.43 g of a mixture of N-dimethylaniline is contacted with pyridine hydrochloride (5.2 g). Bring the mixture to 190 ° C 6
Heat for 0 minutes. HPLC analysis of the mixture indicated the presence of 2,6-dichloroaniline (43%) and 2-bromo-3-chloroaniline (57%).

Example 20 Pyridine hydrochloride (4.35 g, 37.7 mmol) was converted to 2,6-dichloro-4-trifluoromethyl-N, N-
Add to dimethylaniline (0.86 g, 3.3 mmol). Heat the mixture to 185 ° C. for 2 hours. HPLC
Analysis showed the presence of 2,6-dichloro-4-trifluoromethylaniline (76 mol%).

Example 21 : Mono-demethylated 2,6-dichloro-4-trifluoromethyl-N, N-
Dimethylaniline (0.86 g, 3.3 mmol) and pyridinium acetate (5 g) are introduced into a jacketed Teflon autoclave (100 ml). The autoclave is sealed and the mixture is heated to 190 ° C. for 2 hours. HP
LC analysis indicated the presence of 2,6-dichloro-4-trifluoromethyl-N-methylaniline (9 mol% yield).

Example 22 : Comparative Example 2,6-Dichloro-4-trifluoromethyl-N, N-
A mixture of dimethylaniline (0.810 g) and dimethylamine hydrochloride (3.5 g) is heated to 180 ° C. for 1 hour. HPLC analysis of the mixture indicated no conversion.

Example 23 2,6-Dichloro-4-trifluoromethyl-N, N-
Dimethylaniline (0.745 g), pyridine hydrochloride (34 mg) and dimethylamine hydrochloride (3.24 g)
Is heated to 180 ° C. for 1 hour. HPL of the mixture
C analysis showed a 20% yield of 2,6-dichloro-4-trifluoromethylaniline. This is three times higher than the theoretical value when only pyridine was active.

Example 24 : Prior art 2,6-dichloro-4-trifluoromethyl-N, N-
Dimethylaniline (1 g) was added to a hydrobromic acid aqueous solution (47
%, 5 g) is refluxed for 5 hours. HPLC analysis of the mixture showed 89% conversion and 55% 2,6-dichloro-4-trifluoromethylaniline yield.

Example 25 : Comparative Example The purpose of this is to illustrate the need for free radical properties. A solution of 2-chloro-6-nitro-N, N-dimethylaniline (0.802 g, 4 mmol) in chloroform (10 ml) is introduced into a 100 ml Teflon reactor. A solution of bromine (0.64 g, 4 mmol) in chloroform (20 ml) is added to the above solution. The mixture is stirred at room temperature for 4 hours. Analysis of the reaction mixture showed that there was nothing other than the starting material (analytical methods: gas chromatography and mass spectrometry).

Example 26 : Comparison with US Patent No. 2,888,514 This demonstrates that the presence of a base is required. Base -free 3,4-dichloro-4-trifluoromethylbenzene (4.62 g, 21.4 mmol) and dimethylformamide (22 g, 14 molar equivalents) were added in that order for 100 m
1) into a jacketed Teflon autoclave. Close the autoclave and stir the mixture for 2 hours.
Heat to 00 ° C. for 5 hours. Analysis of the reaction medium by gas chromatography showed 3% conversion for a 2% dimethylaniline yield. Presence of base 3,4-Dichloro-4-trifluoromethylbenzene (4.62 g, 21.4 mmol), dimethylformamide (22 g, 14 molar equivalents) and solid sodium hydroxide (0.856 g, 2.5 molar equivalents) ) In that order to 10
Introduce into a 0 ml jacketed Teflon autoclave. The autoclave is sealed and the mixture is heated with stirring to 200 ° C. for 5 hours. Analysis of the reaction medium by gas chromatography showed a 95% yield of 3-chloro-4-trifluoromethyldimethylaniline of 80%.
Conversion rate.

Example 27 : Example of a method for the regeneration and recycling of pyridinium compounds. Pyridine hydrochloride can be prepared by methods known to the person skilled in the art, for example by treating pyridine with a stoichiometric amount of a 36% aqueous hydrochloric acid solution and then with water. Can be easily obtained by azeotropic distillation with toluene. Method 2,6-Dichloro-4-trifluoromethyldimethylaniline (1.72 g, 6.6 mmol) was added at 180 ° C. in the presence of pyridine hydrochloride (8.7 g, 37.7 mmol).
For 1 hour. Analysis of the reaction showed 100% conversion. The reaction medium is then cooled to 140 DEG C. and o-xylene (5 ml) is added with stirring. After 2 minutes, the stirring is stopped and the two layers separate. Collect the upper layer. Analysis by gas chromatography showed 2,6-dichloro-4-trifluoromethylaniline (1.47).
g, 97% yield). The lower layer containing methylpyridinium hydrochloride and pyridinium hydrochloride was
It is regenerated by the action of ammonia at 0 ° C. The pyridine recovered by distillation can be recycled.

Continuation of the front page (56) References US Patent 2,875,514 (US, A) Chemische Berichte, (1967) 100 (7) 2131-2137 Synthesis, Jan (1980) p. 39-41 (58) Field surveyed (Int. Cl. ⁷ , DB name) C07C 209/10 C07C 211/52 C07B 61/00 CA (STN)

Claims (2)

(57) [Claims] (1) The following formula (I): (Where R ₁ is selected from chlorine and bromine , R ₂ is hydrogen, halogen and the following formula: R- (CX ₂ ) n- (III) (where R is halogen and X is halogen
Wherein n is at least 1) , R ₃ is selected from hydrogen and halogen, R ₄ is hydrogen, halogen and the following formula: R- (CX ₂ ) n- (III) (where R is halogen and X is each halogen
Wherein n is at least 1) , R ₅ is selected from hydrogen and halogen, R ₆ is hydrogen, halogen and the following formula: R- (CX ₂ ) n- (III) (where R is halogen and X is each halogen
And n is at least 1) . Provided that the groups R ₂ , R ₆ and R ₄
At least one of which is assumed to be electron-withdrawing by an inducing effect) in the presence of a base in the range of 150 to 3
Including the step of reacting with a dialkylamide at a temperature of 00 ° C, comprising the following formula (II): (Wherein R ₁ represents a mono- or dialkylamino group, and R ₂ , R ₃ , R ₄ , R ₅ and R ₆ have the above-mentioned meanings). 2. The process according to claim 1, wherein the reaction is carried out in the presence of copper, and the copper is introduced in the form of a cuprous salt.