CA2070386A1

CA2070386A1 - Process for the preparation of fluorobenzenes and fluorotoluenes

Info

Publication number: CA2070386A1
Application number: CA 2070386
Authority: CA
Inventors: Heinz Litterer; Frank P. Sistig; Ernst I. Leupold
Original assignee: Individual
Current assignee: Hoechst AG
Priority date: 1989-10-27
Filing date: 1990-10-18
Publication date: 1991-04-28
Also published as: WO1991006523A1; DE3935861A1; JPH04506356A; EP0496752A1

Abstract

Process for the preparation of fluorobenzenes and fluoro-toluenes Abstract A process for the preparation of fluorobenzenes and fluorotoluenes of the formula (I), in which X is H or a methyl group, R1, R2 and R3 are, independently of each other, at least one of the radicals H, F, Cl and C1-C3-alkyl, at least one of these radicals being fluorine, and S1 and S2 are, independently of each other, H and/or radicals which reduce the electron density at the benzene nucleus, but preferably H, characterized in that benzal-dehydes of the formula (II) in which R1, R2, R3, S1 and S2 have the meaning given above, are reacted of a catalyst, activated by treatment with hydrogen, comprising at least one transition metal of subgroups VII to VIII of the Periodic-Table, at 150 to 600°C.

Description

2~386 Description Proces~ for the preparation of fluorQbenzenes and fluoro-toluenes The present invention relates to a process for the preparation of substituted or unsubstituted fluoro-benzenes and/or substituted or unsubstituted fluoro-toluenes from the corresponding fluorobenzaldehydes. The substituted or unsubstituted fluorobenzenes and fluoro-toluenes are important intermediates, for example in the preparation of pharmaceutical products.

Hitherto, fluorobenzenes have been prepared from the corresponding substituted or unsubstituted anilines by diazotization and subsequent replacement of the diazo group by fluorine. Thus the synthesis of fluorobenzene by diazotization of aniline hydrochloride, conversion of the resulting benzenediazonium chloride into the tetra-fluoroborate and subsequent heating has long been known (G. Balz and G. Schiemann, Ber. 60 [1927] 1186, 1188;
D.T. Flood, Org. Synth. Coll. Vol. II tl943~ 295).
1,3~Difluorobenzene could be obtained analogously by heating benzene-1,3-bisdiazonium tetrafluoroborate in a yield of 31~, relative to the m-phenylenediamine as the starting compound (G. Schiemann and R. Pillarsky, Ber. 62 [1929] 3035-3043, especially 3039). The diazotization of 3-fluoroaniline in anhydrous hydrogen fluoride in the presence of either ammonium fluoride or tertiary amines or dimethyl ~ulfoxide likewi e led to 1,3-difluoro-benzene. The yields were reported as 46 to 73%
(US-A 4,075,252 and US-A 4,096,196).

Similarly low yield~ (27 to 40%) were obtained by G. 9alz and R. Pillarsky (loc. cit.) for the prepara~ion of 1,4-difluor~benzene from p-phenylenediamine.

The thermal decomposition of the substituted benzene-diazonium hexafluorophosphates in place of the tetra-20703~
wo 91/06523 - 2 - PCT/EP90/01763 1uoroborates resulted in many cases in higher, but still not economically satisfactory, yields of the correspond-ing fluorobenzenes (K.G. Rutherford et al., J. Org. Chem.
26 [1961] 5149-5152).

Fluorinated toluenes are obtained analogouSly from the corresponding C-methyl-substituted anilines.

The decarbonylation of aromatic aldehydes on catalysts containing a metal of the platinum group was described by J. Smolik and M. Kraus (Collect. Czech. Chem. Commun. 37 [1972] 3042-3051).

It has also been proposed (DE Application No. 38 24 141.2) to prepare fluorobenzenes by catalytic decarbonylation on zeolite catalysts from the corresponding fluorobenzal-dehydes. The preparation of fluorotoluenes from fluoro-benzaldehyde~ is only possible by this process by start-ing from fluoromethylbenzaldehydes.

By means of the invention it is now possible to prepare fluorobenzenes or fluorotoluenes as desired from the fluorobenzaldehydes.

The present inven~ion relates to a process by which benzaldehydes of the formula (II) (see Patent Claim 1), in which R1, R2 and R3 are, independently of each other, hydrogen, $1uorine, chlorine and/or Cl-C3-alkyl, at least one of these radicals being fluorine, and S1 and s2 are, independently of each other, hydrogen and~or radicals which reduce the electron density at the aromatic nucleus, such as chlorine, but preferably hydrogen, are reacted at 150 to 600C on a catalyst, activated by treatment with hydrogen, comprising at least one trans-ition metal of subgroups VII to VIII of the PeriodicTable of Meyer/Mendeleev, to give compounds of the formula (I) (see Patent Claim 1), in which X is H or a methyl group and Rl, R2, R3, Sl and s2 have the meaning given above. If the reaction i~ carried out without a 207038~
WO 91/06523 - 3 - PCT/EPgO/01763 carrier gas or with a carrier gas which is inext, under the reaction conditions, to the compounds participating in the reaction, decarbonylation to the corresponding fluorobenzenes principally ensues, whereas, using hydro-S gen as the carrier gas, hydrogenation to the correQpond-ing fluorotoluenes principally takes place. The prepara-tion of fluorotoluenes from fluorobenzaldehydes requires the presence of hydrogen.

The catalysts suitable for the process according to the invention contain one or more elements of subgroups VII
to VIII, i.e. manganese, rhenium, iron, cobalt, nickel, ruthenium, rhodium, palladium, osmium, iridium or plat-inum, preferably platinum and/or cobalt and/or platinum and rhenium. They can be applied to the usual supports, such as Al2O3, silica gel or activated charcoal. The catalysts employed can be in principle also all conven-tional zeolites which have been doped by Lmpregnation, ion exchange or other conventional methods with an element of subgroups VII to ~III. The catalysts used according to the invention are employed advantageously in the form of moldings or extrudates. Fluidized-bed catalysts can also be used.

The process according to the invention is preferably carried out at temperatures from 180 to 440C. I~ can be carried out both in the liquid phase and, preferably, in the gas phase. In the gas-phase reaction, a carrier gas such as nitrogen or C02 or, especially when the prepara-tion of fluorotoluenes is envisaged, hydrogen can also be admixed.

The total pressure i~ generally between 0.1 and 100 bar, preferably between 1 and 20 bar. Particularly preferably, however, the pressure employed is atmospheric or the backpressure resulting from the transport of the gaseous starting materials through the for example fixed catalyst.

The weight hourly space velocity (unit weight of the starting material per hour and per unit weight of the catalyst - dimension: h~l ~ = WHSV = Weight aourly Space Velocity) is preferably between 0.1 and 10 h-1.

The gas mixture leaving the reaction zone can be worked up by conventional separation methods, for example by cooling using fractional condensation. Preferably, however, the desired reaction products are obtained in pure form by distillation.

In the following examples, U denotes conversion rate, SDFB the selecti~ity for 1,3-difluorobenzene and SDFT the selectivity for 2,4-difluorotoluene.

Examples 1 to 5~ A tube reactor having a diameter of 30 mm and a length of 600 mm was charged with 34 g (S0 ml) of a commercial catalyst containing approxLmately 0.5% by - weight of platinum and approximately 0.3% by weight of rhenium on aluminum oxide as support. Hydrogen ~25 l/h) and 2,4-difluorobenzaldehyde (14 ml/h) were passed over the heated catalyst bed. The reaction products were cooled and the condensed fractions were analyzed by gas chromatography. The following results were obtained:

Example T/C U/% SDFB SDFT
l 195 99 8 92 6) In the apparatus described in ~xample l, 50 ml of the catalyst mentioned there were treated for 3 hours at 350C with hydrogen and subsequently the trial from ~ID70386 Example 1 was repeated using an identical quantity of nitrogen instead of hydrogen at 440C. 1,3-Difluoro-benzene was formed virtually exclusively during this procedure at a conversion rate of 50% (SDFB = 99~) 7 to 9) If, in place of the catalyst used in Examples 1 to 6, a catalyst containing approxLmately 0.5% by weight of palladium on SiO2 as a support was used and the procedures of Examples 1 to 5 were otherwi~e followed, the following results were obtained:

Example T/C U/~ SD~ SDFT

10) A tube reactor having a diameter of 20 mm and a length of 600 mm was charged with a catalyst, which had been prepared ~y extruding 50~ by weight of finely-powdered cobalt and 50% by weight of ~-Al203 to form extrudates having a diameter of 2 mm, and the catalyst was treated for 3 hours at 300C with hydroqen. Using nitrogen (lS l/h) as the carriex gas, at 400C and a WHSV
of O.S h-l, 1,3-difluorobenzene was obtained with a 6elec-tivity of 99~ in addition to traces o~ 2,4-difluoro-toluene, at a conversion rate of the 2,4-difluorobenz-aldehyde of 45~.

11 to 14) Repetition of the trial described in Example 10 using hydrogen (15 l/h) as the carrier ga~ instead of nitrogen produced the following values:

3 O EXamP1e T/ C U/ 96 SDFB SDFT

12 316 2~ 10 88 14 4~0 28 23 68 WO 91/06523 - 6 - PCT/~ 907/~
15 to 17) The tube reactor described in Example 10 was charged with 20 ml of an extruded rhodium/zeolite cata-lyst containing 1% by weight of rhodium. This catalyst had been prepared from zeolite H-ZSM 5 (SiO2/Al2O3 = 90) by ion exchange with RhC13-xH20 (38% Rh), subsequent drying at 110C, calcining at 350C and subsequent treating for three hours with hydrogen at 350C. 2,4-Di-fluorobenzaldehyde was then passed through the reactor at 10 ml per hour in a hydrogen stream of 15 1. The follow-ing results were obtained:

Example TtC U/~ SD~SDFT
-18 to 20) If, in place of the catalyst used in Examples 15 to 17, a catalyst containing 2.5% by weight of rhodium on ~-Alz03 was used, and the procedures of Examples 15 to 17 were otherwise followed, the following results were obtained:

Example T/C U/% SDF~ SDF~

21) If, in place of the catalyst used in Examples 15 to 17, a catalyst containing 1~ by weight of platinum on a charcoal support was used, and the procedures of Examples 15 to 17 were otherwise followed, 1,3-difluorobenzene was selectively obtained in the reaction of 2,4-difluoro-benzaldehyde in a flow of nitrogen at 370C.

22 to 25) The tube reactor described in Example 10 was charged with 20 ml of a platinum/zeolite catalyst. This catalyst had been prepared from 100 g of zeolite H-ZSM 5 (SiO2/Al2O3 = 90) by impregnating with a solution of 1.65 ~ of tetraammine platinum(II) chloride in 300 ml of water, subsequent drying at 110C, calcining for four hours at 350C and subsequent treating for three hours with hydrogen at 350C. 2,4-Difluorobenzaldehyde was then S passed through the reactor at 10 ml per hour in a hydrogen stream of 15 l. The following results were obtained:

Example T/C V/% SDF~ SDFT
.

26) A tube reactor having a diameter of 50 mm and a lS length of 600 mm was charged with 20 ml of a granulated catalyst containing 5% by weight of rhodium on activated charcoal as support. 2,4-Difluorobenzaldehyde was passed through the reactor at 15 ml per hour in a nitrogen stream of 15 1 at 165C. 1,3-Difluorobenzene was obtained in a selectivity of 99% at a conversion rate of 40~.

27 to 29) In the tube reactor described in Example 1, 20 ml of the platinumtrhenium catalyst mentioned there were arranged. 2-Chloro-6-fluorobenzaldehyde was then passed through the reactor at 10 ml per hour in a hydro-25 gen stream of 15 l. The followin~ results were obtained:

Example T/C U/% S~ S~T
-S~ = selectivity for 1-chloro-3-fluorobenzene S~T = selectivity for 2-chloro-6-fluorotoluene 30) If, in a trial set-up as described in Example 1, a catalyst was used which contained approximately 5% by weight of nickel on an al~minum oxide support, at a temperature of 470C, a WHSV of 0.78 h~1 and a hydrogen carrier gas stream of 15 l/h, 1,3-difluorobenzene and 2,4-difluorotoluene were obtained in a weight ratio of S about 13:1 at almost complete conversion, but with markedly decreased selectivity.

Claims

Patent Claims:

1. Process for the preparation of fluorobenzenes and fluorotoluenes of the formula (I) (I) in which X is H or a methyl group, R1, R2 and R3 are, independently of each other, at least one of the radicals H, F, Cl and C1-C3-alkyl, at least one of these radicals being fluorine, and S1 and S2 are, independently of each other, H and/or radicals which reduce the electron density at the benzene nucleus, preferably H, characterized in that benzaldehydes of the formula (II) (II) in which R1, R2, R3, S1 and S2 have the meaning given above, are reacted on a catalyst, activated by treatment with hydrogen, comprising at least one transition metal of subgroups VII to VIII of the Periodic Table, at 150 to 600°C in the presence of hydrogen.

2. Process according to Claim 1, characterized in that the catalyst contains cobalt, platinum and/or plati-num/rhenium.

3. Process according to Claim 1 or 2, characterized in that the reaction is carried out in the gas phase.

4. Process according to one or more of Claims 1 to 3, characterized in that a temperature of 180 to 440°C
is employed.

5. Process according to Claim 3 or 4, characterized in that the total pressure employed is 0.1 to 100 bar, advantageously 1 to 20 bar, preferably atmospheric pressure, or the backpressure resulting from the transport of the gaseous starting materials through the catalyst system.