Preparation of .alpha.-methylsubstituted carbonyl compounds

A process for the preparation of .alpha.-methylsubstituted ketones by reacting the corresponding non-methylsubstituted ketones with formaldehyde under hydrogenating conditions. The reaction proceeds easily and with good yields if a catalyst containing metallic palladium deposited on a zirconium, hafnium, titanium or tin phosphate is used. The products are valuable intermediates for the preparation of dyes, crop protection agents or drugs.

The present invention relates to a process for the preparation of 
.alpha.-methylsubstituted ketones by reacting the corresponding 
non-methylsubstituted ketones with formaldehyde under hydrogenating 
conditions. 
The introduction of methyl groups in the .alpha.-position to a carbonyl 
group is known per se. For example, Houben-Weyl, Methoden der organischen 
Chemie, Volume VII, 2b, page 1385 et seq. describes the alkylation of 
carbonyl compounds by reaction with alkyl halides, preferably with the 
bromides or iodides. Disadvantages of this method are that alkyl halides, 
which are relatively expensive, are used as starting compounds and that 
alkaline substances which can often only be employed in combination with 
expensive solvents, such as an alkali metal amide in liquid NH.sub.3, are 
used, mostly in stoichiometric amounts. 
A further conventional method is to carry out an aldol condensation of the 
carbonyl compound with formaldehyde, dehydrate the aldol adduct formed and 
then hydrogenate the resulting .alpha.,.beta.-unsaturated carbonyl 
compound to give the desired end product. It is true that the formaldehyde 
used is a cheap starting material but the reaction must be carried out in 
two or three separate steps, in different apparatuses. 
A single-step alkylation, wherein a ketone is reacted with methanol over a 
copper or silver catalyst to give the corresponding 
.alpha.-methylsubstituted ketone is described in German Patent 2,257,675. 
Disadvantages of this process are that dialkylated and/or polyalkylated 
compounds are also formed, and that in some cases the yields are rather 
poor. For example, when reacting methyl ethyl ketone with methanol, the 
product contains not only methyl isopropyl ketone but also similar amounts 
of ethyl isopropyl ketone and diethyl ketone. Furthermore, even a certain 
proportion of diisopropyl ketone is formed. 
Further, German Published Application DAS No. 1,922,755 discloses the 
self-condensation of ketones to give novel ketones having twice the number 
of carbon atoms, for example the preparation of methyl isobutyl ketone 
from acetone. The catalyst used is a Zr, Hf, Ti or Sn phosphate, 
additionally containing small amounts of palladium. 
We have found, surprisingly, that these catalysts are also useful in the 
reaction of carbonyl compounds with formaldehyde. This was unexpected 
since it had to be assumed that on using these catalysts a 
self-condensation of the particular carbonyl compound would occur 
preferentially. Instead, we have found that when a mixed condensation, 
i.e. a condensation of a carbonyl compound with formaldehyde, is carried 
out over such a catalyst, the self-condensation occurs to only a 
negligible extent even if a large excess of the carbonyl compound is 
employed. 
Accordingly, the invention relates to a process for the preparation of a 
carbonyl compound of the general formula I 
##STR1## 
where R.sup.1 and R.sup.2 are straight-chain or branched alkyl of 1 to 8, 
preferably 1 to 4, carbon atoms or are aryl or aralkyl, R.sup.1 may also 
be H and R.sup.1 and R.sup.2 together with the carbon atoms between them 
may also be members of an alicyclic ring, wherein a ketone of the general 
formula II 
##STR2## 
is reacted with formaldehyde at 50.degree.-230.degree. C. in the presence 
of hydrogen and of a catalyst in which the active constituents are 
(a) a phosphate of one or more of the metals zirconium, titanium, hafnium 
and tin or a mixture of such phosphates and 
(b) metallic palladium deposited on this phosphate (or phosphate mixture). 
The ketones of the formula II required as starting compounds are 
conventional commercial compounds. Examples include acetone, methyl ethyl 
ketone, diethyl ketone, cyclohexanone, acetophenone and 
4-phenyl-butan-2-one. 
The catalysts used in the novel process are disclosed in German Published 
Application DAS No. 1,922,755. They essentially consist of a phosphate of 
zirconium, hafnium, titanium or tin and additionally contain metallic 
palladium. There are no limits on the molar ration PO.sub.4.sup.3- : 
metal, but for reasons of economy metal phosphates in which the said ratio 
is from 3:1 to 1:3 are generally employed. Catalysts in which the molar 
ratio PO.sub.4.sup.3- : metal is from 0.6:1 to 1.7:1 are particularly 
advantageous. The amount of metallic palladium is not critical and is 
essentially decided by economic considerations. It is generally from 0.1 
to 5.3% by weight, especially from 0.2 to 3.0% by weight, based on metal 
phosphate. The catalysts are prepared in a conventional manner as 
described in great detail in the above German Published Application, to 
which reference may be made. The catalyst may be employed as powder or as 
beads, pellets, tablets or granules. 
The formaldehyde introduced into the reaction may be in a variety of forms. 
For example, it is possible to use paraformaldehyde dissolved or suspended 
in the carbonyl compound to be converted, or to employ commercial 
formaldehyde solutions, eg. a 30-40% strength solution of formaldehyde in 
water or in a lower alcohol. 
The molar ratio of the carbonyl compound to be converted, of the formula 
II, to formaldehyde is not critical. Particularly good results are 
obtained if the carbonyl compound is used in excess. The molar ratio 
employed can vary from 1:1 to 20:1; preferably the molar ratio is from 1:1 
to 15:1. An even higher excess in general offers no advantages and is 
therefore ruled out on economic grounds. It is noteworthy however that 
even with a higher excess of the carbonyl compound, self-condensation only 
occurs to a slight degree. 
The novel process may be carried out continuously or batchwise. For 
continuous industrial operation, it is technologically advantageous to use 
a fixed catalyst bed in a reaction column and to pass the mixture together 
with hydrogen over the bed. For batchwise operation, it is advantageous to 
use the catalyst in suspension. 
In principle the process may be carried out even at atmospheric pressure 
but in order to increase the reaction rate it is advantageous to operate 
under super-atmospheric pressure, especially where low-boiling carbonyl 
compounds are employed. Usually, the hydrogen pressure is up to 100 bar; 
even higher pressures in general offer no advantages and are therefore 
uneconomical. Economically the most advantageous results are achieved at 
pressures of from 1 to 50 bar. 
The reaction temperature used is advantageously from 50.degree. to 
230.degree. C., preferably from 70.degree. to 210.degree. C. Below 
50.degree. C., the reaction rate drops substantially whilst above 
230.degree. C. there is a loss of yield due to continuing aldol 
condensations. 
Where the carbonyl compound to be reacted is liquid, it is not necessary to 
use a solvent. Solid carbonyl compounds may be dissolved in any liquids 
which are inert under the reaction conditions, for example in paraffins, 
e.g. pentane, hexane and octane, cycloparaffins, e.g. cyclohexane, 
aromatics, eg. benzene and toluene, alcohols, e.g. methanol, ethanol and 
isopropanol, or esters, e.g. methyl acetate and ethyl acetate. 
Using the novel process, .alpha.-methylsubstituted carbonyl compounds, 
which are mostly valuable intermediates for the preparation of dyes, crop 
protection agents or drugs, may be prepared in a technically simple and 
advantageous manner.

EXAMPLE 1 
A catalyst which has been prepared as described in German Published 
Application DAS 1,922,755 (compare Table 1) by precipitating an aqueous 
solution of appropriate amounts of ZrOCl.sub.2.8H.sub.2 O, PdCl.sub.2 and 
H.sub.3 PO.sub.4 by means of aqueous ammonia, followed by a reduction 
treatment, and which consists of zirconium phosphate with an added 0.5% by 
weight of metallic palladium was introduced, in the form of pills of 
diameter 3 mm, into a tubular reactor having a capacity of 1.8 liters and 
an internal diameter of 4.5 cm. 2.5 liters per hour of a mixture which 
consisted of 87.8% of methyl ethyl ketone and 12.2% of aqueous (30% 
strength by weight) formaldehyde solution were passed, at 180.degree. C., 
through this tubular reactor, which was under a hydrogen pressure of 30 
bar. 
The reaction product obtained under these conditions was collected and 
subjected to fractional distillation; the fractions obtained were analyzed 
by gas chromatography. This indicated the following composition 
(neglecting the water employed and formed): 
______________________________________ 
unconverted 
##STR3## 85.6% by weight 
##STR4## 9.7% by weight 
##STR5## 0.8% by weight 
##STR6## 1.0% by weight 
##STR7## 0.1% by weight 
______________________________________ 
This corresponds to a yield of methyl isopropyl ketone of 82.9%, based on 
formaldehyde employed. If the methyl isopropenyl ketone (the intermediate 
in the formation of methyl isopropyl ketone) is included, the yield is 
89.7%. It is noteworthy that the proportion of 2,3-dimethylhexan-2-one 
formed, this being the self-condensation product of methyl ethyl ketone, 
is virtually negligible. 
EXAMPLE 2 
1.0 liter per hour of a mixture which consists of 82.5% of methyl ethyl 
ketone and 17.5% of an aqueous 30% strength formaldehyde solution was 
reacted at 170.degree. C., under 30 bar H.sub.2 pressure, in the 
apparatus, and over the catalyst, described in Example 1. The yield of 
methyl isopropyl ketone obtained was 77.7%, based on formaldehyde 
employed. If the methyl isopropenyl ketone obtained is included as a 
useful product, the yield is 84.1%. The proportion of 
2,3-dimethyl-hexan-2-one formed under the conditions described was 0.2%. 
EXAMPLE 3 
0.4 liter per hour of a mixture of 68.4% of methyl ethyl ketone and 31.6% 
of an aqueous 30% strength formaldehyde solution was reacted, under 30 bar 
H.sub.2 pressure, in the apparatus, and over the catalyst, described in 
Example 1. At a reaction temperature of 190.degree. C., the yield of 
methyl isopropyl ketone was 78.9% based on formaldehyde employed. If the 
methyl isopropenyl ketone is included, the yield is 83.2%. Once again, the 
proportion of 2,3-dimethyl-hexan-2-one formed was low, namely 0.1%. 
EXAMPLE 4 
1.0 liter per hour of a mixture of acetone and aqueous 30% strength 
formaldehyde solution (the molar ratio of acetone to formaldehyde being 
8:1) was reacted at 160.degree. C. under 40 bar H.sub.2 pressure in the 
reactor described in Example 1, over a catalyst consisting of titanium 
phosphate plus 0.5% of Pd. Methyl ethyl ketone was obtained in a yield of 
73.3% based on formaldehyde employed. The proportion of methyl isobutyl 
ketone formed, this being the dimerization product of acetone, was 0.8%. 
EXAMPLE 5 
0.5 liter per hour of a mixture of acetophenone and a 30% strength solution 
of formaldehyde in isobutanol (the molar ratio of acetophenone to 
formaldehyde being 8:1) was reacted at 180.degree. C., under 30 bar 
H.sub.2 pressure, in the apparatus, and over the catalyst, described in 
Example 1. The yield of propiophenone obtained was 52.8%, based on 
formaldehyde employed. 
EXAMPLE 6 
0.5 liter per hour of a mixture of cyclohexanone and a 30% strength 
solution of formaldehyde and isobutanol (the molar ratio of cyclohexanone 
to formaldehyde being 6:1) was reacted, at 180.degree. C. under a hydrogen 
pressure of 30 bar, in the apparatus, and over the catalyst, described in 
Example 1. The desired product 2-methylcyclohexanone was obtained in 45.3% 
yield, based on formaldehyde employed.