DD152538A5 - PROCESS FOR PRODUCING SUBSTITUTED BENZALDEHYDE - Google Patents

Abstract

The invention relates to a process for the preparation of substituted benzaldehydes of the formula I, wherein R & exp1! Hydrogen o. Halogen and R & exp2! Represents halogen or optionally halogen-substituted phenoxy. The aim of the invention is to increase the yield compared to known processes. The object of the invention is to provide a novel process for the preparation of substituted benzaldehydes which can be used as intermediates in the production of pesticides. The process is characterized in that alpha-hydroxybenzylphosphonic acid esters of the formula II are reacted with alkali metal or alkaline earth metal hydroxides in the presence of water and optionally further thickening agents at temperatures between 0 and 100.degree.

Description

_ _Ä Berlin, 5. 7. 1980

223374 _-5772712

Process for the preparation of substituted benzaldehydes Field of application of the invention

The invention relates to a novel process for the preparation of substituted benzaldehydes using novel intermediates.

Characteristic of the known technical solutions

It is known that certain substituted benzaldehydes, such as. As A-fluoro-S-phenoxy-benzaldehyde, obtained when benzyl halides, such as. B. 4-fluoro-3-phenoxybenzylbromid, reacted with hexamethylenetetramine and the product of this reaction with acids heated (see OE-OS 2,709,264).

In this synthesis method, however, a number of substituted benzaldehydes are obtained only in low yields; The yields are also unsatisfactory in the synthesis of the benzyl halides to be used as starting materials, for example by reaction of phenoxytoluenes with N-bromo-succinimide.

Object of the invention

It is the object of the invention to eliminate these disadvantages.

Explanation of the essence of the invention

The invention has for its object to provide a novel process for the preparation of substituted benzaldehydes using new intermediates.

223374 -2-

Subject of the present invention are

1) a process for the preparation of substituted benzaldehydes of the formula

R ¹

^ 2

in which

R is hydrogen or halogen and

2 R is halogen or optionally

halogen-substituted phenoxy is /

characterized in that dT-hydroxy-benzylphosphonic the formula II

O OH ^ R ¹

in which

and the two radicals

1 2

R and R have the meanings given above

Le A 19 866

223374

R individually represents alkyl or phenyl or together represent alkanediyl (alkylene),

with alkali or alkaline earth metal hydroxides in the presence of water and optionally further diluents at temperatures between 0 and 100 "C;

2) new <* f-hydroxy-benzyl ~ phosphonic acid esters of the formula

O OH ^^ R (R ³ O) ₂ P-iH-ß £ _(I1 ,

in which

12 * ϊ

R, R and R are as defined above;

3) a process for the preparation of Q ^ -Hydroxybenzyl-phosphonic acid esters of the formula II (above), characterized in that benzoylphosphonic esters of the formula III

in which

Le A 19 866

223374

R, R and R have the meanings given under (1),

with hydride complexes of the formula

M (M ¹ H ₄ ) (IV)

in which

M is lithium, sodium or potassium and M ^{1 is} boron or aluminum,

optionally in the presence of a buffering agent. and optionally using diluents at temperatures between -2O and + 50 ° C.

Surprisingly, by the process 1) according to the invention, combined with the process 3) for the preparation of the new starting compounds, the substituted benzaldehydes (I) can be prepared substantially more simply, less expensively and in better yields than by known processes.

For example, 3-phenoxy-benzoyl-phosphonic acid dimethyl ester and sodium borohydride are used as starting materials in the process set forth under 3) and in the reaction of the oC-hydroxyl: y-3-phenoxybenzylphosphonic acid dimethyl ester formed in this reaction the procedure set forth under 1) ("Process I)") potassium hydroxide as Reaktionskompanente, the reaction sequence can be outlined by the following equation:.

Le A 19 866

223374

NaBH ₄

KOH

Process 1) is carried out in the presence of water and optionally further diluents. Besides water, alcohols, e.g. Methanol or ethanol can be used. Particularly preferred are two-phase systems of water and water-immiscible solvents, such as z. Hexane, heptane, cyclohexane, methylene chloride, toluene or xylene. Alkali or alkaline earth hydroxides which can be used in process I) are known e.g. Sodium, potassium, magnesium and calcium hydroxide. Preferably, sodium hydroxide is used.

The temperature is kept in process 1) between 0 and 10 ° C, preferably between 10 and 10 ° C. The process is generally carried out at atmospheric pressure.

For carrying out process 1), the compounds of the formula (II) and the alkali metal or alkaline earth metal hydroxides are employed in approximately equimolar amounts. In a preferred embodiment, an aqueous solution of alkali or alkaline earth metal hydroxide is placed under an inert gas atmosphere,

Le A 19 866

223374

"For example, under nitrogen, a water-immiscible solvent and a compound of formula (II) was added thereto and the mixture was stirred for several hours Aufarbeit-ing, which can be carried out by conventional methods, for example, with one with water miscible solvent, such as toluene, extracted, the extract is dried, filtered and concentrated The remaining crude product can be purified by vacuum distillation.

The novel ciT-hydroxy-benzyl-phosphonic acid esters to be used as starting compounds in process 1) are defined by formula (II). Preferably, R is hydrogen or fluorine in p-position and

2 R for bromine or, if appropriate, fluorine-substituted phenoxy in m-position and

R individually is Cj-C-alkyl or phenyl or together for 2,2-dimethyl-propane-1,3-diyl.

Examples of the new intermediates of the formula (III) are:

oC -hydroxy-3-phenoxybenzyl,

<* -Hydroxy-3-bromo-4-fluorobenzyl, Ot -hydroxy-4-fluoro-3-phenoxy-benzyl, <A-hydroxy-3- (4-fluoro-phenoxy) -benzyl and <* - Hydroxy-4-fluoro-3- (4-fluoro-phenoxy) -benzyl-phosphonic acid dimethyl ester and diethyl ester and 2-0xo-2- (<* -hydroxy-3-phenoxy-benzyl) -, 2-0x0-2- (<* -hydroxy ^ ^ fluoro phenoxy-benzyl) - 2-0xo-2- (Ot-hydroxy-3- (4-fluoro-phenoxy) benzyl) - and 2-0x0-2- (cK - hydroxy-4-fluoro-3- (4-fluoro-phenoxy) -benzyl

"5,5-dimethyl-1,3,2-dioxaphosphorinane.

Le A 19 866

223374

Process 3) for the preparation of the novel compounds of formula (II) is preferably carried out using diluents. As such, for example, water and / or alcohols, e.g. Methanol or ethanol in question. Particularly preferred are two-phase systems of water and water-immiscible solvents, such as e.g. Hexane, heptane, cyclohexane, methylene chloride, chloroform, ethylene chloride, diethyl ether, toluene or xylene.

Buffering agents which can be used in the method 3) of the invention for "maintaining the pH at about 6-7 include sodium dihydrogen phosphate and potassium dihydrogen phosphate.

Examples of the hydride complexes of the formula (IV) which are to be used as reducing agent in process 3) are lithium tetrahydridoaluminate (lithium alanate) and sodium borohydride (sodium borohydride). The latter is preferably used.

The reaction temperature is maintained in process 3) between -2o and + 5o ° C, preferably between -Io and + 3o ° C. The process is generally carried out at atmospheric pressure.

In order to carry out process 3), 1 mol of benzoyl phosphonic acid ester of the formula (III) is used between o, 2 and 0.5 mol, preferably between o, 25 and o, 4 mol hydride complex of the formula (II). In a preferred embodiment of process 3), the hydride complex of formula (IV), preferably

Le A 19 866

223 37 ^

"" O -

Sodium tetrahydridoborate, presented in a two-phase mixture of water and a water-immiscible solvent and the benzoyl-phosphonic ester, optionally dissolved in a water-immiscible solvent, metered. The reaction mixture is stirred until the end of the reaction, the organic phase is then separated off, dried, freed from the solvent by vacuum distillation and distilled ¹¹ , ie evacuated for some time at a slightly elevated temperature.

The products of formula (II) are thus obtained relatively pure in oily form.

The benzoyl phosphonic acid esters to be used as starting compounds in process 3) are defined by formula (in).

In this formula, R , R, R and η are preferably the radicals mentioned as being preferred for the compounds of the formula II.

Examples of the intermediates of the formula (III) which may be mentioned: 3-BrOm- ^ fluoro-benzoyl, 3-phenoxy-benzoyl, 4-fluoro-3-phenoxy-benzoyl, 3- (4-fluorophenoxy) benzoyl and 4-fluoro-3- (4-fluoro-phenoxy) -benzoyl-phosphonic acid dimethyl ester and diethyl ester, and 2-oxo-2- (3-phenoxybenzyl) -, 2-oxo-2- (4 fluoro-3-phenoxybenzoyl), 2-0xo-2- (3- (4-fluoro-phenoxy) -benzoyl) and 2-oxo-2- (4-fluoro-3- (4-fluoro-phenoxy) benzoyl) -

• -SiS-dimethyl-1H-dioxaphosphorinane.

he A 19 866

223374 _

Benzoylphosphonsäureester are partly the subject of a non-published patent application (Vergi P 2 916 224 / Le A 19 599). They are obtained by reacting phosphorous acid esters of the formula V.

(R ³ O) ₂ P-OR ⁴ (V)

in which

R has the abovementioned meaning and R 'represents methyl or ethyl,

with Benzoesäurehalogeniden of formula VI

R ¹ (VI)

R ² in which

1 2

R and R have the meanings given above and Hai for fluorine, chlorine or bromine, preferably

stands for chlorine,

at temperatures between 0 and 150 ° C, preferably between 20 and 100 "C.

In the formulas (V) and (VI), R ¹ , R ² and R ^{3 have} the same preferred meanings as in formula (II),

As examples of the phosphorous acid esters of the formula (V) are trimethyl phosphite, triethyl phosphite and 2-ethoxy-5,5-dimethyl-1,3,2-di'oxaphosphorinan mentioned.

.Le A 19 866

22337

Examples of the benzoic acid halides of the formula (TV) which may be mentioned are: 3-bromo-4-fluoro-benzoyl chloride, 3-phenoxy-benzoyl chloride, 4-fluoro-3-phenoxy-benzoyl chloride, 3- (4-fluoro-phenoxy) -benzoyl chloride and 4-fluoro-3- (4-fluoro-phenoxy) benzoyl chloride. These

Some compounds are known or can be prepared analogously to known processes.

Thus, 3-phenoxy benzoyl chloride is known from GB-PS 1 052 390.

The fluorine-substituted Phenoxybenzoesäurehalogenide not yet described in the literature obtained when, according to the following reaction scheme correspondingly substituted Brombenzoesäuren (or their alkali salts) with Alkaliphenolaten in the presence of a catalyst such. Copper oxide, and using "• 5 phenol as a diluent at temperatures between loo and 25o ° C, preferably between 15o and 2oo ° C converts (see the unpublished patent application P 2,915,738 / Le A 19 59o) and the phenoxybenzoic acids formed in this case with a halogenating agent, such as thionyl chloride, at temperatures between 2o and loo ° C: '

Hal-CO - </

Le A 19 866

223374. _u _

The benzaldehydes to be prepared by the process according to the invention can be used as intermediates for the preparation of pesticides (cf. DE-OS 2,621,433).

Le A 19 866

223 37

Example 1;

98 g (ο, 3 mol) of dimethyl α-hydroxyfluorophenoxybenzylphosphonate and 2,000 ml of toluene are added to a solution of 12 g (o, 3 mol) of sodium hydroxide in 2oo ml of water under a nitrogen atmosphere. The reaction mixture is stirred for about 3 hours, with the pH going back to about 9. The toluene phase is separated, dried, filtered and concentrated. The remaining product is purified by vacuum distillation. This gives 48 g (74% of theory) of 4-fluoro-3-phenoxy-benzaldehyde boiling at 86 ° C / o, ol mbar

 Elemental analysis: calc .: C 72.2% H 4.2% Found: C 71.3% H 4.2%

Example 2:

0 OH

A solution of 13o g (o, 4 mol) of dimethyl 4-fluoro-3-phenoxy-benzoylphosphonsäure in 2oo ml of methylene chloride is cooled to O ⁰ C, intensively stirred mixture of 4.8 g (o, 12 mol ) Sodium borohydride, 2oo ml of methylene chloride and 4oo ml of water added dropwise. The reaction mixture is stirred for 9o minutes at ^{0 0} C, then separates, the organic phase from and

Le A 19 866

223374

Extract the aqueous phase with 2oo ml of methylene chloride. The combined methylene chloride phases are dried, filtered and the solvent is carefully distilled off. This gives 12o g (92% of theory) ot -hydroxy-4-fluoro-3-phenoxy-benzyl-phosphonic acid dimethyl ester as a viscous oil

 Elemental analysis:

calc .: C 55.2% H 4.9% P 9.5% Found: C 55, o% H 4.9% P 9.4%

10 Example 3:

62 g of trimethyl phosphite are added dropwise at an internal temperature of 6o to 65 ⁰ C to 126 g (o, 5 mol) of 4-fluoro-3-phenoxybenzoyl chloride. The reaction mixture is stirred for one hour at 8o ° C and evacuated. This gives 158 g (97% of theory) of 4-fluoro-3-phenoxybenzoyl-phosphonic acid diraethylester as a viscous oil

 Elemental analysis:

Calc .: C 55.6% H 4.3% P 9.6% Found: C 55, o% H 4.3% P 9.7%

Le A 19 866

223374

Example 4:

A mixture of 31 g (0.1 mol) of dimethyl d-hydroxy-3-bromo-4-fluorobenzylphosphonate, 4 g (0.1 mol) of sodium hydroxide, 8o ml of water and 8o ml of ligroin is added during two hours Room temperature stirred. Then the organic phase is separated, dried and filtered. From the filtrate, the solvent is carefully distilled off under reduced pressure, whereupon the product gradually crystallizes. This gives 18 g (89% of theory) of 3-bromo-4-fluoro-benzaldehyde of melting point 32-33 ° C.

OH

Example 5; ()

A solution of .94 · g (o, 3 mol) of 3-bromo-4-fluoro-benzoylphosphonsäure dimethyl ester in loo ml of methylene chloride is cooled to O ⁰ C, stirred thoroughly mixture of 5 g Natriumtetrahydridoborat, 15o ml of methylene chloride and 3oo ml of water added dropwise. The reaction mixture is stirred for 9o minutes at ^{0 0} C, then separating the organic phase and extracted. the aqueous phase with 2oo ml of methylene chloride. The Ver-

Le A 19 866

223374

The combined methylene chloride phases are dried and filtered. From the filtrate, the solvent is carefully distilled off under reduced pressure. After rubbing with ligroin, the product crystallizes. This gives 75 g (8o% of theory) ° C-Hydroxy-3-bromo-4-fluoro-benzyl-phosphonic acid dimethyl ester of melting point 91-93 ⁰ C.

Example 6: (CH, O) ₂ P-C0-3-F

38 g of trimethyl phosphite are added at an internal temperature between 35 and 4o ° C to a solution of 72 g (o, 3 mol) of 3-bromo-4-fluoro-benzoyl chloride in loo ml of methylene chloride and the reaction mixture is stirred for three hours. Then, the solvent is carefully distilled off under reduced pressure. This gives 92 g (98% of theory) of dimethyl S-bromo-A-fluoro-benzoylphosphonate of boiling point 122 ° C / o, mbar.

Le A 19 866

Claims (1)

223374 Invention claim: Process for the preparation of substituted benzaldehydes of the formula I R ¹ (D in which R ^{1 is} hydrogen or halogen and R is halogen, or optionally halogen-substituted phenoxy, characterized in that Q ^ -hydroxy-benzylphosphonsäureester of formula II 0 OK R ¹ in which the two remainders R and R have the meanings given above, and R individually represents alkyl or phenyl or together represent alkanediyl (alkylene), with alkali or alkaline earth metal hydroxides in the presence of water and optionally further diluents at temperatures between 0 and 100 * C.