Preparation of .alpha.-methyl-substituted ketones

.alpha.-Methyl-substituted ketones are prepared by reacting the corresponding unsubstituted ketones, which must possess two or more geminal hydrogen atoms in the .alpha.-position, with methanol in the gas phase at from 350.degree. to 500.degree. C. and under from 1 to 20 bar in the presence of a metal oxide.

The present invention relates to a novel process for the preparation of 
.alpha.-methyl-substituted ketones by reacting the corresponding 
unsubstituted ketones with methanol in the gas phase in the presence of a 
metal oxide. 
It is known that higher ketones can be synthesized from the corresponding 
lower homologs. In the case of chain extension by one carbon atom 
(methylation), the ketone used as the starting material can be subjected 
to an aldol reaction with formaldehyde, water eliminated from the adduct 
formed, and the resulting .alpha.,.beta.-unsaturated ketone subjected to a 
hydrogenation reaction at the C--C double bond. 
In another possible procedure, for example, the particular ketone to be 
reacted is converted to its enolate, which is methylated with a 
methylating reagent such as methyl halide or dimethyl sulfate (cf. 
Houben-Weyl Methoden der organischen Chemie, 4th edition, Volume 7/2b, 
page 1385 et seq.). 
The disadvantages of the stated proceses are the use of bases, some of 
which furthermore are very expensive, and the use of highly toxic 
substances (eg. dimethyl sulfate). Moreover, the vast majority of these 
processes are multi-stage processes in which the desired products are 
often formed only in poor yields and with poor selectivity. 
J. Chem. Soc. Chem. Commun. 1984, 39, discloses the reaction of acetone 
with methanol in the gas phase over a supported iron catalyst whose 
carrier consists of magnesium oxide. In this process, methanol acts as a 
vinylating agent, ie. the principal product of the reactions described 
therein is methyl vinyl ketone. The by-products formed include methyl 
ethyl ketone and undefined saturated and unsaturated ketones of 5 carbon 
atoms, as well as fairly large amounts of isopropanol, which has 
presumably been formed as a result of the transfer of hydrogen from 
methanol to acetone. 
According to the above publication, other ketones which possess hydrogen 
atoms in the .alpha.-position would also be expected to react with 
methanol to give the corresponding vinyl ketones. 
In contrast, we have found that, surprisingly, methanol does not act as a 
vinylating agent, and -methyl-substituted ketones of the general formula 
##STR1## 
where R.sup.1 is unsubstituted or substituted aryl or hetaryl or a 
tert.-alkyl radical, and R.sup.2 is hydrogen or straight-chain or branched 
alkyl of 1 to 12 carbon atoms, or R.sup.1 and R.sup.2 together form an 
unsubstituted or substituted alkylene group --(CH.sub.2).sub.n --, where n 
is an integer from 3 to 13, are advantageously obtained, if the 
corresponding unsubstituted ketone, which must possess two or more geminal 
hydrogen atoms in the .alpha.-position, is reacted with methanol in the 
gas phase at from 350.degree. to 500.degree. C. and under from 1 to 20 bar 
in the presence of a metal oxide selected from the group consisting of the 
oxides of the metals cerium, chromium, iron, magnesium and manganese. 
The reaction products are .alpha.-methyl-substituted ketones of the above 
general formula in which R.sup.1 is an unsubstituted or substituted aryl 
or hetaryl radical or tert.-alkyl, and R.sup.2 is hydrogen or 
straight-chain or branched alkyl of 1 to 12 carbon atoms, or R.sup.1 and 
R.sup.2 together form an unsubstituted or substituted alkylene group 
--(CH.sub.2).sub.n --, where n is an integer from 3 to 13. 
Examples of aryl radicals are phenyl and naphthyl, an examples of hetaryl 
radicals are pyridyl, pyrimidyl, pyrrolyl, furyl and thienyl. These 
radicals may be substituted or unsubstituted, suitable substituents being 
lower alkyl radicals, such as methyl, ethyl, isopropyl or butyl. 
Examples of tert.-alkyl radicals are tert.-butyl, tert.-pentyl and 
1,1-dimethylbutyl. 
R.sup.1 is preferably a phenyl or pyridyl radical which is unsubstituted or 
substituted by a lower alkyl group, or is preferably tert.-alkyl. 
R.sup.2 is, for example, hydrogen, methyl, ethyl, propyl, isopropyl, butyl, 
sec.-butyl or tert.-butyl. 
Where R.sup.1 and R.sup.2 together form an alkylene radical 
--(CH.sub.2).sub.n --, n is a integer from 3 to 13, preferably 3, 5, 6 or 
10. The alkylene radical may be unsubstituted or monosubstituted, 
disubstituted or polysubstituted, suitable substituents being lower alkyl 
radicals, eg. C.sub.1 -C.sub.6 -alkyl, such as methyl, ethyl, isopropyl or 
butyl. 
A special type of substitution of the alkylene radical consists in 
bridging, for example with formation of a bicyclic system. 
Particular examples of alkylene radicals --(CH.sub.2).sub.n -- are 
propylene, pentylene, hexylene and decylene. 
The starting materials used are the corresponding unsubstituted ketones, 
which must possess two or more geminal (ie. bonded to the same carbon 
atom) hydrogen atoms in the .alpha.-position. 
Where two geminal hydrogen atoms are present in the .alpha.-position, a 
methyl group is incorporated at this position in the process according to 
the invention (in the formula, R.sup.2 is alkyl). Further methylation is 
not observed. 
Where the ketones used as starting materials possess three geminal hydrogen 
atoms in the .alpha.-position (methyl ketones), it is possible for either 
one methyl group (R.sup.2 is H in the formula) or two methyl groups 
(R.sub.2 is methyl in the formula) to be selectively incorporated at this 
position. 
Usually, the monomethyl product is first selectively obtained in this case. 
By a suitable choice of reaction conditions, for example a longer 
residence time in the reactor or a higher reaction temperature, it is also 
possible to obtain the dimethyl product directly. 
In the case of cyclic starting ketones, the methylation can take place in 
the .alpha.- and .alpha.,.alpha.'-positions. 
##STR2## 
Cyclopentanone, cycloheptanone, cyclooctanone and cyclododecanone can be 
methylated or bismethylated, with good selectivities, in the .alpha.- and 
.alpha.,.alpha.'-positions, respectively. The ratio of the two products 
can be varied by changing the temperature and residence time. By recycling 
the monomethyl derivative, the selectivity can be shifted completely to 
the .alpha.,.alpha.'-dimethylcycloalkanone. A high selectivity with 
respect to the monomethyl derivative can be achieved by low conversion of 
the starting material (see below). The most important by-products are 
.alpha.,.beta.-unsaturated ketones and cycloalkanols presumably formed as 
a result of hydrogen transfer from the methanol to the ketone. This also 
explains the low selectivity when cyclohexanone is used; aromatization 
results in phenol, o-cresol and 2,6-dimethylphenol. .alpha.- and 
.beta.-tetralone likewise tend to undergo aromatization. In contrast, 
geminally disubstituted cyclohexanone can be methylated in good yields: 
##STR3## 
When the ketones containing a six-membered ring are not geminally 
disubstituted, there is a tendency to aromatization. 
If a bicyclic starting ketone is methylated, a mixture of endo- and 
exo-.alpha.-methylcamphor in a molar ratio of 3:1 is obtained, as shown in 
the equation below: 
##STR4## 
The cycloalkanols are preferably reacted with an excess of methanol in the 
presence of water at 400.degree.-480.degree. C., in particular 
400.degree.-450.degree. C., preferably over a magnesium oxide catalyst. 
The process according to the invention is carried out in the presence of a 
catalyst, ie. a metal oxide selected from the group consisting of the 
oxides of the metals cerium, chromium, iron, magnesium and manganese. 
Examples are cerium(IV) oxide, chromium(III) oxide, iron(III) oxide, 
magnesium oxide and manganese(II) oxide, magnesium oxide being preferably 
used. 
The preparation of these metal oxides is known, the products being 
commercially available. As is usual in catalyst technology, they are 
advantageously employed in the molded state, for example in the form of 
tablets, extrudates, pills, spheres or rings. 
The novel process is carried out in the gas phase at from 350.degree. to 
500.degree. C., preferably from 400.degree. to 450.degree. C., and under 
from 1 to 20 bar, preferably under atmospheric pressure. 
The molar ratio of the two reactants, ie. the ketone and methanol, is from 
1:1 to 1:10, preferably from 1:2 to 1:4. 
In some cases, it is advantageous to effect the reaction in the presence of 
water, the latter preferably being added in an amount such that the molar 
ratio of water to ketone is from 1:1 to 5:1. 
The novel process is advantageously carried out as follows: a mixture of 
the reactants in the stated molar ratio, in the presence or absence of 
water, is first fed continuously to an evaporator, where complete 
vaporization is effected. In this procedure, the resulting gas mixture is 
brought to a temperature which is similar to the reaction temperature 
required in the reactor. Advantageously, however, a somewhat higher 
temperature is chosen in the evaporator in order to compensate for any 
heat losses which may occur on the way to the reactor. 
The gas mixture then enters the reactor, which has been heated to the 
required reaction temperature. A tube reactor which contains the catalyst 
is advantageously used as the reactor. 
The space velocity chosen is typically, for example, from 250 to 450 ml 
(based on the state of liquid aggregation) of liquid reaction mixture per 
liter of catalyst per hour , but is not restricted to this range. 
The residence time in the reactor is about 6-5 sec. In the case of double 
methylation (see above), it is advisable to to maintain a residence time 
of about 6-20 sec. 
The gaseous reaction mixture leaving the reactor is then condensed, after 
which it can be purified by fractional distillation. 
The advantage of the novel process is the controlled course of the 
reaction, ie. by-products, such as the toxic vinyl ketones and their 
polymers or the alcohols formed by hydrog n transfer from methanol to the 
ketone, are produced in only small amounts. 
Moreover, the excess amount of methanol used is substantially smaller than 
that usually employed in the prior art. 
Finally, the conversion of the ketone used is very high (from 65 to 100%), 
while at the same time the desired products are formed with high 
selectivity. This is surprising since the known process (loc. cit.) gives 
only poor selectivities at low conversion (not more than 37.2%), and the 
selectivities usually decrease further as the conversion increases. 
The methylated ketones obtained by the novel process are useful 
intermediates for the synthesis of crop protection agents. Some of them 
are also important as scents.

The examples which follow illustrate the invention. 
EXAMPLE 1 
120 ml/hour (corresponding to 92.5 g/hour) of a mixture of 100 g of 
2,2-dimethylbutan-3-one, 128 g of methanol and 18 g of water were 
vaporized continuously, and the vapor passed over 400 ml of magnesium 
oxide in tablet form. The resulting gaseous reaction product was 
condensed, and analyzed by gas chromatography. When methanol and water had 
been stripped off, the following results were obtained (in % by weight): 
______________________________________ 
Reaction temperature 
410.degree. C. 
425.degree. C. 
______________________________________ 
2,2-dimethylpentan-3-one 
61.5 62.0 
2,2,4-trimethylpentan-3-one 
3.9 4.1 
2,2-dimethylbutan-3-one 
24.8 20.9 
______________________________________ 
EXAMPLE 2 
120 ml/hour (corresponding to 103 g/hour) of a mixture of 134 g of 
propiophenone, 128 g of methanol and 18 g of water were vaporized 
continuously, and the vapor passed over 400 ml of magnesium oxide in 
tablet form. The resulting gaseous reaction mixture was condensed, and 
analyzed by gas chromatography. When methanol and water had been stripped 
off, the following results were obtained (in % by weight): 
______________________________________ 
Reaction temperature 
420.degree. C. 
460.degree. C. 
______________________________________ 
1-phenyl-2-methylpropan-1-one 
46.6 64.7 
propiophenone 34.1 15.8 
______________________________________ 
EXAMPLE 3 
120 ml/hour (corresponding to 101 g/hour) of a mixture of 121 g of 
3-acetylpyridine, 320 g of methanol and 36 g of water were vaporized 
continuously, and the vapor passed over 400 ml of magnesium oxide in 
tablet form. The resulting gaseous reaction mixture was condensed, and 
analyzed by gas chromatography. When methanol and water had been stripped 
off, the following results were obtained (in % by weight): 
______________________________________ 
Reaction temperature 
400.degree. C. 
420.degree. C. 
______________________________________ 
1-pyrid-3-ylpropan-1-one 
-- -- 
1-pyrid-3-yl-2-methylpropan-1-one 
67.2 48.0 
1-pyrid-3-yl-2-methylpropan-1-ol 
19.3 26.5 
3-acetylpyridine -- -- 
______________________________________ 
EXAMPLES 4 TO 8 
In Examples 4 to 8, cyclic ketones were employed. The particular 
cycloalkanone, together with an excess of methanol and in the presence of 
water, was passed over the MgO catalyst with various residence times. The 
temperature was from 400.degree. to 450.degree. C. Conversions and 
selectivities are summarized in the Table below. 
TABLE 1 
______________________________________ 
.alpha.-alkylation of cycloalkanones 
Ring size 
Conversion 
Selectivity [%] 
(n + 2) [%] Monomethyl Dimethyl 
.SIGMA. 
______________________________________ 
5 82 40 36 76 
6 93 21 25 46 
7 88 24 48 72 
8 80 46 30 76 
12 94 46 33 79 
______________________________________ 
##STR5## 
EXAMPLE 9 
2-Methylcyclopentanone is an intermediate for an aroma. In the methylation 
of the cyclopentanone, the reaction temperature, the residence time and 
the molar ratio of the reactants were varied in order to investigate the 
effect of these parameters on conversion and selectivity. The results are 
summarized in Table 2 below. 
TABLE 2 
______________________________________ 
Variation of the process parameters in the preparation 
of 2-methylcyclopentanone 
Tem- Selectivities [%] 
pera- Resi- Molar ratio Con- 
ture dence time 
CH.sub.3 OH:cyclo- 
version 
.alpha.- 
.alpha.,.alpha.'- 
[.degree.C.] 
[sec] pentanone [%] Methyl 
Dimethyl 
______________________________________ 
400 4 15:1 70 20 15 
400 2 15:1 55 25 11 
420 2 15:1 75 16 19 
400 5 5:1 54 32 9 
420 5 5:1 69 24 12 
420 6 2:1 41 47 8 
420 7 1:1 27 60 4 
440 7 1:1 36 61 6 
460 7 1:1 46 59 6 
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