The present invention concerns a process for the production of 3-nnethyl-pyridine (3-
picoline) from formaldehyde, paracetaldehyde, ammonia and acetic acid.
3-picoline is a colourless, flammable liquid which is used as a solvent, for the
production of medicaments and insecticides as well as for the synthesis of nicotinic
acid and nicotine amide.
Several synthetic routes for the production of 3-picoline are known in the art, which
are generally based on an addltion/cyclization reaction of aldehyde/keten mixtures
with an ammonia compound. Said reactions can run in the gas phase or in the liquid
phase as well as using a catalyst.
The process according to the present invention is based on the publication of
Grayson, J. and Dinkel, R., "An improved Liquid-Phase Synthesis of Simply
Alkylpyridines", Helvetica Chimica Acta, Vol. 67 (1984), p. 2100-2110.
The authors of this publication describe in table 2, p. 2108 inter alia the synthesis of
3-picoline from acetaldehyde an formaldehyde, whereby different ammonia sources
are compared with regard to 3-picolin yield as well as to the presence of diverse,
unwanted side products.
In particular, it is shown that the use of ammonia acetate results in a yield of 44%,
whereby 3-ethylpyridin as the main side product is present in an amount of 18%.
Thus, the technical problem to be solved is to improve the process of Grayson and
Dinkel with regard to 3-picolin yield, reduction of 3-ethylpyridine amount as main side
product as well as an increase in the space/time yield.
Said problem is surprisingly solved by the process according to the present invention
for the synthesis of 3-methyl-pyridine from formaldehyde, paracetaldehyde, ammonia
and acetic acid, whereby said compounds are reacted and said process comprises
the following parameters:
a) a reaction temperature of 260-300°C;
b) a molar ratio of formaldehyde and paracetaldehyde of 0.7-1-4 Mol/Mol:
c) an ammonia concentration of 10-20 weight-%
d) an acetic acid concentration of 4-20 weight-%
e) a paracetaldehyde concentration of 0.4-1.6 Mol/kg
f) a retention time of 10-30 minutes in case of a continuous reaction and 10-90
minutes in case of a discontinuous reaction; and
g) a reaction pressure of 30-130 bar
It may be preferred that the reaction takes place in a reactor. More preferably, said
reactor is a system with a high efficiency of mixing like stirring devices as well as
continuous flow-through stirrer vessels and discontinuous stirrer vessels. Most
preferably, said reactor is a loop-reactor or jet-loop-reactor.
Loop- and jet-loop-reactors according to the invention are characterized by the fact
that the respective reactants are brought to reaction with the catalyst-solution in a
continuous manner. One major advantage of jet-loop-reactors compared to stirrer
vessels for the production of 3-picoline is the more intensive and faster mixing of
fluids when operating under a high circulation stream, resulting in an increased
passage of heat and material. Preferably, the process according to the invention is
operated in a loop reactor with stream zones. Another advantage of stream-powered
loop reactors is a finer dispersion of the added phases and thus a bigger specific
interphase.
Furthermore, it may be preferred that side products are removed in the process of recycling
the catalyst. Generally, all technical means known in the art can be employed,
like e.g. extraction and rectification. Especially preferred is distillation.
The process according to the invention contemplates the addition of ammonia and
formaldehyde both in molecular form as well as in form of their addition product
hexamethylene-tetratimne (Urotropine).
3>
The process according to the invention is distinguished from the prior art according to
Dinkel et al. inter alia by combining a higher selectivity with regard to the formation of
3-methylpyridine with an increased space/time yield. This results in a major technical
advantage, since normally an increased space/time yield results in a decrease in
selectivity.
The process according to the present invention is further explained by the following,
non-limiting example.
Example 1
The reaction takes place continuously in a 100 Litre reactor with a very high degree
of mixing. Pumps are used to add the catalyst solution (a mixture of water, ammonia
and acetic acid) and the educts (paracetaldehyde and formalin).
261 kg/h of catalyst solution (75 weight-% water, 15 weight-% ammonia and 10
weight-% acetic acid) are brought into the reactor via high-pressure pumps.
Simultaneously, 13 kg/h paracetaldehyde and 26.8 kg/h formalin solution (37.4
weight-%) are added continuously via high-pressure pumps. The reactor temperature
is kept at 278°C and the reactor pressure at 100 bar. A retention time of 20 minutes
results in a crude solution containing 10.02 kg/h 3-picolin and 0.37 kg/h 3-
ethylpyridine. Under these condition, a 3-picolin yield of 64.6% (based on
formaldehyde) and a 3-ethylpyridine yield of 3.5% (based on acetaldehyde) is
achieved. All pyridine bases were analyzed via gas chromatography.

We Claim:
1.) A process for the synthesis of 3-methyl-pyridine from formaldehyde,
paracetaldehyde, ammonia and acetic acid, whereby said compounds are
reacted and said process comprises the following parameters:
a) a reaction temperature of 260-300°C;
b) a molar ratio of formaldehyde and paracetaldehyde of 0.7-1-4
Mol/Mol:
c) an ammonia concentration of 10-20 weight-%
d) an acetic acid concentration of 4-20 weight-%
e) a paracetaldehyde concentration of 0.4-1.6 Mol/kg
f) a retention time of 10-30 minutes in case of a continuous reaction and
10-90 minutes in case of a discontinuous reaction; and
g) a reaction pressure of 30-130 bar
2.) A process according to claim 1, whereby said process takes place in a
reactor system with a high efficiency of mixing
3.) Process according to claim 2, whereby said reactor system is a continuous
or discontinuous flow-through stirrer vessel.
4.) Process according to claim 2, whereby said reactor system is a loop-reactor.
5.) Process according to at least one of claims 1-4, whereby side products are
removed in the process of re-cycling the catalyst.
6.) Process according to claim 5, whereby said side products are removed via
rectification or extraction.
7.) Process according to at least one of claims 1-6, whereby the space/time
yield of 3-methylpyridine is more than 50 kg/m^^h, preferably more than 80
kg/m^*h and most preferably more than 100 kg/m^*h.
8.) Process according to at least one of claims 1-7, whereby the 3-
methylpyridine yield is at least 64% (based on formaldehyde) and the 3-
ethylpyridine yield is at most 4% (based on paracetaldehyd).
Dated this the 17^*" day of January, 2012