The present invention provides a process for the preparation of alkylpyridines. In particular, the present invention provides an improved process for the preparation of alkylpyridines by reacting pyridine with an alkylating agent in the presence of a heterogenous catalyst. The process of the present invention has high selectivity and conversion rate and uses less amount of catalyst along with minimum effluents.
BACKGROUND OF INVENTION:
Alkylpyridines, in particular, methylpyridines and their derivatives are industrially valuable compounds. They are used as raw materials in fine chemicals, bulk drugs, insecticides, fungicides and herbicides. Increasing demands for the production of methylpyridines and their derivatives exceeds that traditionally obtained from coal tar distillation. Attempts have therefore been made to develop synthetic processes for these chemicals commercially.
Yakugaku Zasshi (1981), 101(1), 20-4 discloses liquid phase methylation of pyrazine and pyridine with nickel catalyst. In this process for 5g of pyridine lg of catalyst is being used. No selectivity/process conditions are mentioned in the document. High amount of catalyst make this process unattractive.
Molecules 2015, 20, 15797-15806 discloses continuous flow synthesis of 2- methyl pyridines via alpha methylation of pyridine using raney nickel and 1-propanol as solvent for substrate dissolution and reaction also. The process is disclosed on HPLC column for isolating small quantities of product. Use of 1-propanol as solvent on commercial scale and smaller scale makes this commercially unattractive.
Japanese patent no. JP5424878 describes the process for methylation of a nitrogen containing heterocyclic 6-membered ring compound. In this patent pyridine reacts

with methanol in the presence of raney nickel catalyst in an autoclave at 250° C for 5 hrs to obtain alpha picoline in yield of 72.3%. In this process for 5g of pyridine lg of catalyst and 15ml of methanol is being used. No selectivity/process conditions are mentioned in the document. High amount of catalyst and methanol make this process unattractive.
J. Org. Chem. 1966, 31, 6, 2008-2009 discloses methylation of pyridine using nickel catalyst M-0104T or M1404T in vapour phase at 295°C to give 57% 2-Picoline and 24% 2,6-Lutidine. In this method methanol (15 times) is used with respect to pyridine which makes this process commercially unattractive.
In research article JACS, 1964, 86, 5355-5356 lg of pyridine with 2 g of W-5 Raney nickel in 20 ml of n-decyl alcohol was refluxed for 12 hours. The amount of catalyst used is double of raw material and use of n-decyl alcohol makes this process commercially highly unattractive.
Synthetic Communications, 2008, 38, 3672-3682, 2008 discloses procedure for the alpha methylation of pyridines. It describes the conversion of pyridine to alkyl pyridine at higher pressure 150 bar and prolonged reaction time 212 hrs. with laborious liquid-liquid extraction process, offering environmentally unfriendly reaction.
Nippon Kagaku Kaishi (1980), (4), 551-6 nickel substituted Y type zeolite (MY) catalyst was used for alkylation of pyridine. Ratio of methanol: pyridine is 8:1.
Zeolites and related microporous materials 1994, 84, 1959-1964 discloses the methylation of pyridine over zeolites such as H-Y, Na-Y, HZSM-5, Mordenite, ZSM-22, MgAlPO-11 and Zeolite Beta. In this for one mole of pyridine 8 moles of methanol is used. Maximum selectivity obtained with MgAlPO-11 is 64%. Higher quantity of solvent and lower selectivity makes this process commercially unfeasible.

Green Chem. 2002, 4, 558-561 discloses the methylation of pyridine to methyl pyridine over the catalyst Mn2Fe204 at 673K with selectivity of 79.5% and 17.5% of 3-methyl pyridine. Preparation of catalyst involves a long process and expensive one. Selectivity is also low.
US patent no. 4658032 assigned to M/s Koei chemicals reveals a process for alkylation of 3,5-lutidine to 2,3,5-collidine using methanol at 190-240° C at 45-60 kg/cm2 pressure. This patent nowhere discusses the alkylation of pyridine.
Indian patent IN222262 discloses a process for preparing 2,4-lutidine, 2,5-lutidine and 2,3,5-collidine. This patent uses raney nickel catalyst for alkylation of beta picoline, gamma picoline and 3,5-lutidine using methanol at temperature 200- 260° C and pressure 30-60 kg/cm2. This patent nowhere discusses the alkylation of pyridine.
The synthetic methods of alkylated pyridine (Picoline) disclosed in above patent/patent applications suffer from one or more of the following shortcomings:
a) Poor selectivity
b) Lower conversion
c) High amount of catalyst w.r.t. pyridine
d) Higher amount of alkylating agent w.r.t. reactant
e) Higher temperature
f) Less information on separation of side products
g) Recyclability of catalyst
In light of the drawbacks of foregoing processes, and increasing demand for producing alkylpyridines, there is a need to develop an alternate commercially and economically viable process for large scale manufacture of alkylpyridines from pyridine. In addition, the process should involve side products which are commercially important so that they can be sold to reduce the manufacturing cost.

In order to obviate the limitations of the prior art, the present invention provides an improved process to produce alkylpyridines from pyridine.
OBJECT OF THE INVENTION:
It is an object of the present invention to provide an improved process for the preparation of alkylpyridines of formula (I),
(I)
wherein Ri represents substituted or unsubstituted C1-C6 alkyl group.
It is another object of the present invention to provide an improved process for the preparation of alkylpyridine of formula (I), with simultaneous generation of N-alkylpiperidine of formula (II).

01) wherein Ri represents substituted or unsubstituted C1-C6 alkyl group
It is another object of the present invention to provide an improved process for the preparation of alkylpyridine of formula (I), wherein the process has high selectivity and conversion rate.
It is another object of the present invention to provide an improved process for the preparation of alkylpyridine of formula (I), wherein the process utilizes less amount of catalyst.

It is another object of the present invention to provide an improved process for the preparation of alkylpyridine of formula (I), wherein the process utilizes less amount of alkylating agent.
It is another object of the present invention to provide an improved process for the preparation of alkylpyridine of formula (I), wherein the catalyst can be recycled.
SUMMARY OF THE INVENTION:
Accordingly the present invention provides a process for the preparation of alkyl pyridines of the formula (I)

where Ri represents substituted or unsubstituted C1-C6 alkyl group, said process comprising reacting pyridine with an alkylating agent in the presence of a heterogenous catalyst wherein the side product, N-alkylpiperidine of formula (II) is formed in an amount less than 15% .
In one embodiment, the selectivity of the reaction is more than 80%.
DETAILED DESCRIPTION OF INVENTION:
It will nevertheless be understood that no limitation of the scope of the invention is thereby intended by way of embodiments and examples. Such alterations and further modifications in the present invention, and such further applications of the principles of the invention as would normally occur to those skilled in the art are to be construed as being within the scope of the present invention.

It will be understood by those skilled in the art that the summary of the invention provided herein is exemplary and explanatory of the invention are not intended to be restrictive thereof. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention belongs. The composition, methods, and examples provided herein are only illustrative and not intended to be limiting.
The terms "comprises", "comprising", or any other variations thereof, are intended to cover a non-exclusive inclusion, such that a process or method that comprises a list of steps does not include only those steps but may include other steps not expressly listed or inherent to such a process or method. Similarly, one or more steps of method or components preceded by "comprises... a" does not, without more constraints, preclude the existence of other, steps or components. Appearances of the phrase "in a preferred embodiment", "in an embodiment", "in another embodiment" and similar language throughout this specification may, but not necessarily do, all refer to the same embodiment.
Alkylpyridines, in particular, methylpyridines and their derivatives are industrially valuable compounds. Ongoing research provides improved process for the preparation of these Alkylpyridines. The improvement can be with respect to yield, purity, better selectivity, eco-friendly process, and better industrial cycles.
From industrial perspective, it is important that the process yields 100% desired product. However it is not practically possible and side products are always formed. Process parameters such as catalyst, reaction time, isolation technique, etc. need to be changed to achieve desired results. It is also desired that side products formed also have commercial significance so that the overall process is eco-friendly and all the side products/solvents etc. are either re-used or commercially exploited.
The inventor of the present invention has found that alkylation of pyridine with alkylating agent using heterogenous catalyst can be optimized to obtain maximum

selectivity of the desired product. If the reaction is proceeded for a longer time, then side products start becoming more due to the presence of hydrogen in the reaction mass and selectivity is reduced. Also N-alkylpiperidines of formula (II) are formed as side products.


^

Catalyst
Alkylkating agent

N
Ri
(II) (Minor)

Accordingly, the present invention provides an improved process for the preparation of alkylpyridine of formula (I),
^
wherein Ri represents substituted or unsubstituted C1-C6 alkyl group, said process comprising treating pyridine with an alkylating agent in the presence of a heterogenous catalyst.
In one embodiment, the present invention provides a process for the preparation of alkyl pyridines of the formula (I)
N (I)
where Ri represents substituted or unsubstituted C1-C6 alkyl group, said process
comprising reacting pyridine with an alkylating agent in the presence of a
heterogenous catalyst wherein the side product, N-alkylpiperidine of formula (II) is
formed in an amount less than 15% .

The alkylating agent that can be used in the present invention are selected from methanol, ethanol, propanol isopropanol and n-butanol. It can also act as solvent medium for the reaction and this reduces the effluent generation of the reaction. The amount of alkylating agent varies from 0.5-5 times of pyridine.
The catalyst that can be used in the present invention are transition metal based catalyst selected from nickel, palladium, platinum, Raney nickel and mixture thereof. It can be unsupported or supported on carrier such alumina, silica, aluminosilicate, activated carbon, zeolites, and mixtures thereof. The amount of catalyst varies from 0.01-25% of pyridine.
As per the process of the present invention, pyridine and catalyst are fed in an autoclave and the reaction is carried out by feeding alkylating agent at the temperature ranging from 150-300° C and pressure 15-75 kg/cm2. The feeding rate of alkylating agent is done at a flow rate of l-20ml/min, preferably 5-10ml/min and more preferably 2-10ml/min. This is important since it also plays a role in selective conversion and leftover unreacted pyridine. The reaction can be carried out in fixed bed reactor or fluidized bed reactor or loop reactor.
As per the process of the present invention, pyridine and alkylating agent can also be fed in an autoclave followed feeding of catalyst at the temperature ranging from 150-300° C and pressure 15-75 kg/cm2.
Pyridine, catalyst and alkylating agent can also be taken together in an autoclave. Reaction mass is heated to 150-300° C and pressure 15-75 kg/cm2.
The reaction is monitored for completion and is optimized to run for a specific time under specific conversion. The reaction time varies between 3-20 hours. After completion of reaction, the autoclave is cooled, reaction product taken out and catalyst is separated. Reaction product is subjected to fractional distillation.

Next recycle batch is taken in an autoclave using same used catalyst along with top up of 10-15% of fresh catalyst.
The process of the present invention is advantageous over the prior art due to higher selectivity of picolines and the utilization of inexpensive and commercially available alkylating agent and catalyst.
Additionally, the process provides the easily separation of commercially important side products from picoline by simple isolation methods. The process is cost effective, involves minimum consumption of pyridine as raw material, solvents and minimum generation of effluents. In addition, the process of the present invention involves reduction in batch cycle time thereby increasing the plant capacity, production and associated profits immensely.
Advantages of the Invention: The present invention provides one or more of the following advantages:
> Selectivity of product formation is very high thereby making the process commercially attractive and feasible.
> Amount of catalyst required is for the alkylation is reduced as compared to prior art.
> Amount of alkylating agent which is used as a solvent also is reduced thereby increasing the batch size and reducing production cost.
> Alkylating agent used is very cheap and commercially available.
> Major side products are unreacted pyridine and N-Methyl Piperidine with a very small amount of 2,6-Lutidine. The side products such as N-methyl pyrrolidine (NMP), 2,6-Lutidine are separated easily and commercially useful.
> Unreacted pyridine is used in next cycle
> Catalyst can be reused several times.

EXAMPLES:
The present invention is not limited to the above embodiments, and the technical solutions of the foregoing embodiments of the present invention can be cross-combined with each other to form a new technical solution. In addition, any technical solution formed by equivalent replacement falls within the protection scope claimed by the present invention. The present invention is specifically explained below with the help of following examples as cited below
EXAMPLE-1 : Preparation of alpha picoline (continuous feeding of methanol)
Pyridine and catalyst were taken in an autoclave and stirred at 850-875 rpm. Autoclave was purged with nitrogen (initial pressure of 4-6 kg/cm2) and heated to 250°C. Methanol was pumped at rate of 3-8 ml/minute in the autoclave using high pressure dosing pump. After the completion of reaction, autoclave cooled to 30-35°C and reaction mass discharged. The product mass analysed by GC (Alpha picoline: 53 %; N-Methyl Piperidine: 12.5%; Unconverted pyridine-15%); Selectivity-84%.
Isolation of Products: The produced reaction mass was subjected to atmospheric fractional distillation using 3.0meter long with one-inch diameter glass column packed with SS wire mesh. Alpha picoline having 99.79 % GC purity was isolated. NMP with 95-99% purity. Methanol having purity of 99.7-99.9% isolated which can be recycled at reaction stage
EXAMPLE-2
Pyridine was taken along with above used catalyst with 4.5 gm of fresh raney nickel in an autoclave and stirring started at 850-875 rpm. Autoclave purged with nitrogen and an initial pressure of 4-6 kg/cm2 maintained. Inside heating increased up to 225-

230°C and pressure increased to 20-25 kg/cm2. Methanol pumped in the autoclave at rate of 3-8 ml / minute using high pressure dosing pump and 55-60 kg/ cm2 pressure obtained. After the completion of reaction, autoclave cooled to 30 -350 C and reaction mass discharged. The product mass analysed by GC, 52 % alpha picoline ; 13% NMP ; 1.0 % 2,6-lutidine 16% unconverted pyridine. 86 % selectivity.
EXAMPLES 3-11: Catalyst Recyclability
Further reaction was carried out up to 10th recycle of used catalyst with top up of 10-15%) fresh catalyst. The conditions and results are summarized in table-2 below. The equipment and procedure was similar to Example-3.
Table-2: Methylation of Pyridine with recycle of used catalyst

Example Reaction Temp. °C Mole ratio Methanol/ pyridine Selectivity
N-Methyl
Piperidine
(NMP) 2,6-Lutidine Alpha picoline
3 225 -230 1.32:1 13.0 1.58 84.6
4 225 -230 1.32:1 12.1 1.62 85.7
5 225 -230 1.32:1 13.4 1.31 84.6
6 225 -230 1.32:1 12.3 1.40 86.0
7 225 -230 1.32:1 12.5 1.67 85.2
8 225 -230 1.32:1 11.8 1.49 85.8
9 225 -230 1.32:1 13.9 1.74 84.0
10 225 -230 1.32:1 13.3 1.86 84.1
11 225 -230 1.32:1 14.2 1.53 83.9

We claim:

1) A process for the preparation of alkyl pyridines of the formula (I)

where Ri represents substituted or unsubstituted C1-C6 alkyl group, said process comprising reacting pyridine with an alkylating agent in the presence of a heterogenous catalyst wherein the side product, N-alkylpiperidine of formula (II) is formed in an amount less than 15% .
2) The process as claimed in claim 1, where the selectivity of the reaction is more than 80%.
3) The process as claimed in claim 1, wherein alkylating agent is selected from methanol, ethanol, propanol isopropanol and n-butanol.
4) The process as claimed in claim 1, wherein heterogenous catalyst is selected from transition metal based catalyst selected from nickel, raney nickel, palladium, platinum and mixture thereof.
5) The process as claimed in claim 1, wherein the alkylating agent is added at a rate of 2-10 ml/minute.
6) The process as claimed in claim 1, wherein the reaction is carried out at a pressure in the range of 20-60 Kg/cm2.
7) The process as claimed in claim 1, wherein the compound of formula (I) is 2-methylpyridine.

8) The process as claimed in claim 1, wherein the N-alkylpiperidine is N-methylpiperidine.
9) The process as claimed in claim 1, where the said reaction is performed in fixed bed reactor or fluidized bed reactor or loop reactor.
10) The process as claimed in claim 1, where the said reaction is performed in batch
or continuous mode.