JPS60130529A - Diazotization and fluorination - Google Patents

Abstract

PURPOSE:To obtain a fluorobenzene derivative or fluoropyridine derivative, by diazotizing an aniline derivative or an aminopyridine, derivative with sodium nitrite in hydrofluoric anhydric, etc., decomposing thermally the reaction product in the presence of a dehydrating agent. CONSTITUTION:A compound shown by the formula I or formula II (R is halogen, alkyl, NO2, COCH3, OH, CN, CHO, etc.; m is 0-3 integer; n is 1 or 2) is diazotized with 1-1.5mol sodium nitrite or potassium nitrite based on 1mol starting compound in hydrofuoric anhydride or a mixed solution of hydrofluoric anhydride and a tertiary amine at -10-10 deg., and then decomposed thermally in the presence of a dehydrating agent (e.g., F2O5, PCl5, or SbF5) at 40-60 deg.C to give a compound shown by the formula III or formula IV. EFFECT:There is no danger of corrosion caused by hydrous hydrofluoric acid, and the desired substance can be prepared in high yield.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing fluorobenzene derivatives or fluoropyridine derivatives by diazofluorination.

Aniline derivatives, aminopyridine derivatives, etc. can be diazofluorinated using sodium nitrite, etc. in hydrofluoric acid or a mixture of hydrofluoric acid and tertiary amine to obtain fluorobenzene derivatives, fluoropyridine derivatives, etc. , U.S. Pat. No. 4,096,196 and others.

The reaction is expressed as follows.

In such conventional methods, a mixture of hydrofluoric acid or tertiary amine is used for reactive melting, but hydrofluoric acid becomes extremely corrosive due to the influence of the water produced, and expensive materials are required for the reactive iron core. However, depending on the reaction conditions, it may not be possible to find a material that can withstand use. on the other hand,
In the reaction itself, the following side reactions are likely to occur due to the influence of the water produced, resulting in a problem of lowering the yield of the target compound.

Recognizing the problems of conventional methods, the inventors of the present invention, such as Yu-ichi and N, have conducted intensive research into a more advantageous method, and as a result, they have conducted diazofluorination in the presence of a dehydrating agent. The inventors have found that this not only alleviates the problem of corrosion caused by hydrofluoric acid, but also increases the yield of the target compound. The derivative or the aminopyridine derivative represented by the general formula (11) is diazo-ized using sodium nitrite or potassium nitrite in an anhydrous solution or in a mixture of anhydrous solution iR and a tertiary amine, and then dehydrated. A diazofluorination method characterized in that a fluorobenzene derivative represented by the general formula (l+l) or a fluoropyridine derivative represented by the -MX formula (N) is obtained by thermal decomposition in the presence of an agent. be.

Rm+(12)n −−−−−−−(1) RIn−0−
Fn-(■.

(In the formula, R is C!1. Br, F, etc.) ・Rogen atom, alkyl group, NO+, 0OOHs, NHOOOH
a, C0OH,OH.

5OsH,SR,'0H2000H,ON, OHO,
One type or a combination of two or three types selected from 0ONHz.

m represents O or an integer of 1 to 3, and n represents an integer of 1 to 2. )
The aniline derivative or aminopyridine derivative used in the present tJJ is an aromatic primary amine or a heteroaromatic primary amine represented by the general formula (1) or (It). R may not be present, and three examples thereof include those having one NH2 group such as aniline and aminopyridine, and those having two NH2 groups such as phenylenediamine and diaminopyridine. Specific examples of the general formula R are C1,
Halogen atoms such as Br, F, alkyl atoms with carbon number ~12, NO2,0OC)TS, NHOOCHs, 0
OOI(, OJ H8Os.

C) IzOOOH, ON, C! One type or a combination of two or three types selected from HO, 0ONHz. Examples of 1 gb are fluoroaniline, aminoisophthalic acid, aminonzorcin, cyamylzorcin, dimethylaminopyridine, acetylaminoaminopyridine, aminoacetophenone, aminoacetanilide, aminobenzoate, aminoethylbenzene 1, aminophenylacetic acid, aminophenol, Examples include aminopropylbenzene, aminobenzonitrile, aminothiophenol, aminobenzaldehyde, and aminobenzamide. Examples of combinations of two to three types include AmicReso-Nishi, Ami/Clo)vphenol, aminosalicylic acid, aminonitrophenol, aminenitrophenolsulfonic acid, and the like.

These aniline derivatives or aminopyridine derivatives (hereinafter referred to as starting compounds) are prepared by adding sodium nitrite or potassium nitrite (hereinafter referred to as diazotizing agent) in anhydrous hydrofluoric acid or a mixture of hydrofluoric anhydride and a tertiary amine. Diazofluorination is carried out using Preferred tertiary amines include pyridine,
There are quinoline, lutidine, N-dimethylaniline, triethylamine, 2-nolambda loviridine, etc., and the use of these has the advantage of facilitating extraction and separation of the target product and reducing tarring reactions. During diazotization, the molar ratio between the starting compound and anhydrous hydrofluoric acid is 1:5 to 1:50, and the molar ratio between the starting compound and the diazotizing agent is 1:1 to 1:1.
．． 5 is suitable, and the reaction temperature is -20 to +20°C, preferably -10 to 10°C. After diazotization, usually
A dehydrating agent is added to carry out thermal decomposition, but a dehydrating agent may be added as appropriate before diazotization. By adding a dehydrating agent, corrosion of equipment during thermal decomposition can be significantly reduced, and the target compound can be obtained in high yield. Preferred dehydrating agents are IJOs, 5bys', 5bO1! , '5
bBrs, SOs, fuming ('51, 5nO14,
Ta11! , PCl5, BFa, etc., but organic dehydrating agents such as acetyl chloride may also be used. The type of dehydrating agent that gives the target compound in good yield varies somewhat depending on the target compound, and a dehydrating agent suitable for y may be selected as appropriate. The addition of 1" of the dehydrating agent varies depending on the structure of the dehydrating agent, but when expressed in molar ratio of the dehydrating agent and sodium or potassium nitrite, it is appropriate to add 1" to 1:5. ~100"C1 preferably 40-60℃
The target compound, a fluorobenzene derivative or a fluoropyridine derivative, can be obtained by thermal decomposition in a temperature range of 200 to 3000, followed by extraction and separation and washing with water. The reaction time and reaction pressure in the diazofluorination reaction and thermal decomposition reaction can be selected as appropriate. The reaction pressure can be not only normal pressure but also high pressure.

According to the method of the present invention, a fluorobenzene conductor or a fluoropyridine derivative in which the Nl2 group of an aniline derivative or an aminopyridine derivative is substituted with F can be obtained in good yield, and it is also possible to prevent corrosion by hydrofluoric acid as in the conventional method. There is no danger and it is extremely advantageous in terms of equipment design and reaction control.

Examples of the present invention will be explained in more detail below.

Example 1 330 t of hydrofluoric anhydride was placed in a cooled 5ue-3+6JJ autoclave with a capacity of 1 L, and 100 t (0,741 mol) of m-aminoacetophenone was added at about θ°C with stirring, followed by addition of sodium nitrite at 5°C or below. 54Pv(0,7
83 mol) was added.

After the addition was completed, phosphorus pentachloride 4e,3F (0.22 mol) was added and the mixture was reacted for 1 hour with stirring. After that, 45-5
Thermal decomposition of the diazonium salt was carried out at a reaction temperature of 5° C. for 6 hours. After the thermal decomposition was completed, the reaction solution was cooled, ice water and methylene chloride were added, and the resulting methylene chloride layer was further washed with water. After washing with water, methylene chloride) was analyzed.
m-Fluoroacetophenone contained ss, 9F (yield: 84).

On the other hand, this reaction was carried out in the presence of a test piece made of Su, S-316 for a one-sided eating test. After the reaction was completed, the surface of the test heath was observed, and no corrosion of the test piece was observed.

Comparison 11i2 Example 1 The reaction was carried out under the same conditions as in Example 1 except for the addition of phosphorus pentachloride, and the reaction yield of m-fluoroacetophenone was 58%. On the other hand, this reaction was conducted in the presence of a test piece made of 8uS-316 for corrosion resistance testing. After the reaction was completed, the surface of the test piece was observed and significant corrosion was observed on the test piece.

Example 2 The cooled 1 was placed in a Bus-3J61J1-toclave, and 3301 (16.5 mol) of hydrofluoric anhydride and 163.1 of pyridine were added. +7 (2.06 mol) and stirred to approx.
'c m-fluoroanily790 yv (0,81
Then, 67.1yv (0,972 mol) of sodium nitrite was added at below 5°C. After the addition is complete, add 57% of phosphorus pentoxide. syv (0,405 mol)
was added, and the mixture was stirred and reacted for 1 hour. Then 45~60°
Thermal decomposition of the diazonium salt was carried out at C for 6 hours. After the thermal decomposition was completed, the reaction solution was cooled, ice water and methylene chloride were added, and the resulting methylene chloride layer was further washed with alkali water. Analysis of the methylene chloride layer after washing with alkaline water revealed that it contained 72yv (yield 7s%) of m-difluorobenzene.

Comparative Example 2 A reaction was carried out under the same conditions as in Example 2 except that phosphorus pentoxide was not added, and the yield of m-difluorobenzene was 64.

Examples 3-7 Various dehydrating agents (9,405 mol) in place of phosphorus pentoxide
Table 1 shows the results of a reaction conducted under the same conditions as in Example 2.

Table 1 Example 8 Hydrofluoric anhydride s 3 or (16, s mol) and pyridine 200 y (2,53 mol) were placed in a cooled autoclave of 5us-31631 with an iz capacity, and the mixture was heated at about θ° C. with stirring. -acetylamino-5-aminopyridine 100
f (0,662 mol) was added, followed by the addition of nitrous acid (0,794 mol) at below 5°C. After the addition is complete, phosphorus pentachloride 68.9F' (0,
331 (#) was added, and the mixture was stirred and reacted for 1 hour. after that,
Thermal decomposition of the diazonium salt was carried out at a reaction temperature of 50-55°C for 8 hours. After the thermal decomposition was completed, the reaction solution was cooled, ice water and methylene chloride were added, and the resulting methylene chloride layer was separated and washed with alkaline water and then with water. Analysis of the methylene chloride layer after washing with water revealed that 2-acetylamino-5-fluoropyridine was present in an amount of 73.43% (yield: 72 pieces).

On the other hand, this reaction was carried out in the presence of a test piece made of 8uS-316 for @ food test, and after the reaction was completed, the surface of the test piece was inspected ξ2, and no corrosion was observed on the test piece.

Comparative Example 3 A reaction was carried out under the same conditions as in Example 8 except that phosphorus pentachloride was not added, and the reaction yield of 2-acetylamino-5-fluoropyridine was 52%.

On the other hand, this reaction was carried out in the presence of a test piece made of 5uS-316 for corrosion resistance testing, and after the reaction was completed, the surface of the test piece was observed, and extensive corrosion of the test piece was observed.

Example 9 Hydrofluoric anhydride 3a oyb (16.5 mol) and N
, 307.6 PV (2.54 mol) of N-dimethylaniline was added, and while stirring, 2-acetylamino-5
-aminopyridine (0,662 mol) was added, followed by
Nitrous acid below 5℃) IJum 57.0p (o, sz
6 mol) was added. After the addition was completed, 71.7 F (0,331 mol) of antimony pentafluoride was added, and the reaction was stirred for 1 hour. Thereafter, the diazonium salt was thermally decomposed at a reaction temperature of 50-60°C for 5 hours. After the thermal decomposition was completed, the reaction solution was cooled, ice water and methylene chloride were added, and the resulting methylene chloride layer was separated and washed with alkaline water and then with water. Analysis of the methylene chloride layer after washing with water revealed that 2-acetylamino-5-fluoropyridine was s3. ep (yield 8
2%) included ~ also.

Examples 10 to 13 Instead of antimony pentafluoride, each H
Table 2 shows the results of a reaction using 331 mol) under the same conditions as in Example 9.

Table 2 Example 14 Anhydrous fluorine 400jl'V (20 mol) was placed in a cooled A-toclave made of 5us-316 with a capacity of 1, and 2-aminobinodine 94yv (1,0
mol) was added, followed by the addition of sodium nitrite (75.9FC1.1 mol) below 5'C. After addition,
Phosphorus pentachloride to4p (o, s mol) was added, and the mixture was stirred and reacted for 1 hour. Thereafter, the diazonium salt was thermally decomposed at a reaction temperature of 50 to 70°C for 10 hours. After pyrolysis,
The reaction solution was cooled, ice water and methylene chloride were added, and the resulting methylene chloride layer was washed with alkaline water for an additional 7 J.
(Washed. Analysis of the methylene chloride layer after washing with water revealed that 2-
It contained 77.65'' (yield 801) of fluoropyridine.

Claims (1)

[Claims] (1) An aniline derivative represented by the general formula (+) or an aminopyridine derivative represented by the general formula (n) is added to a submersible solution in hydrofluoric anhydride or a mixture of hydrofluoric anhydride and tertiary amine. A fluorobenzene derivative represented by the general formula (1H) or a fluoropyridine derivative represented by the general formula (IV) is obtained by diazotizing it using IJ or potassium nitrite (nitric acid) and then thermally decomposing it in the presence of a dehydrating agent. A diazofluorination method characterized by obtaining. l(m -Q-(NH2)n -----1--(1)R
m-< and (NH2)n --------(11) R4F
n---------(III) Rm + Fn (Iy) (wherein, R is 01. Br, a halogen atom such as F, an alkyl group, No, 0OOHm, NHCOCH3,
0OOH. OH, H80I, SH, 0H2000H, ON, C
! f (one or a combination of two or three selected from O, 0ONHz; m is 0 or an integer of 1 to 3; n is an integer of 1 to 2;
2. The diazofluorination method according to claim 1, wherein the glaze is a mixture of glaze or more.