Title of Invention

"AN IMPROVED PROCESS FOR THE PREPARATION OF PYRIDINE/ SUBSTITUTED PYRIDINE DERIVATIVE"

Abstract

An improved process for the preparation of pyridine/substituted pyridine derivative which comprises heating acetaldehyde 25-29 wt%, formaldehyde IS18 wt%, water 27-3 wt%, ammonia 18-21 wt% and methanol 0-15 wt% to a temperature in the range of 300-400*' C, contacting the gaseous reactants so obtained with a zeolite based catalyst having silica to alumina ratio greater than 12 and containing 1 to 6% of mixture of oxides of metals of group II, III, IV or VIII of the periodic table at a temperature in the range of 350-500 C maintaining the contact time in the range of 0.5 to 5 seconds, collecting the resultant product and subjecting to extraction with an aprotic organic solvent by conventional methods such as herein described separating the organic layer by known methods to obtain pyridine/substituted pyridine derivative.

Full Text

This invention relates to an improved process for the preparation of pyridine/substituted pyridine derivative. This invention particularly relates to an improved process for the production of pyridine and 3-picoline by reacting acetaldehyde, formaldehyde and ammonia in the presence of a zeolite based catalyst. In recent years the demand of pyridine compounds has been steadily going up mainly because of increase in production of pharmaceuticals and agrochemicals. At present the total annual demand of pyridine and 3-picoline in the country is approximately around 3000 tonnes. Pyridine is the parent of a series of compounds that is important in medicinal, agricultural and industrial chemistry. Most of the pyridine derivatives are prepared by manipulation of pyridine and its homologues. i he main outlet for pyridine is in the production of antihistamines like Decapryn, pheniramin and chloropheniramine which are derivatives of 2-benzoylpyridine. Chlorothen, Hibernon, Methapyridine, pyribenzamine and Nilorgex which are based on 2-aminopyridine, stimulants like Ritaline, Meratrin; disinfectants and sterilizers. Pyridine is widely used in formulation of certain weed killers as Diquat and parquet and as herbicide (Reglone and Gramoxone) in agro-chemical industries. It is also used as waterproofing agent in textile industry as a surface active agent. 3-picoline is mainly used in pharmaceutical fields. It is used for the production of nicotinic acid and nicotinamide which are extensively used to combat vitamin-B deficiency. It is also used as an intermediate for the preparation of useful drugs such as antispasmodic. One of the commercial sources of pyridine bases is tar and liquor obtained by the carbonisation of coal. Crude base is only 1.9-3% in tar comprising very little amount of pyridine and picoline whose separation is very difficult. The beta picoline cut which consists of beta picoline and gamma picoline having almost same boiling points cannot be separated in pure form. However, these pyridine and picolines may not be suitable for pharmaceutical purpose due to high sulphur content in coal. The prior art processes (e.g. DSP's 3,272, 825; 3, 946,020; Japanese patents 76-63, 176; 69-32, 790; Great Britain patent 1,141,526; USP's 4,220,783 and 3,723,408; Ind.Eng.Chem. 47,789,1955) comprise the catalysts containing alumina, amorphous silica-alumina and also in .some cases crystalline aluminosilicate in acidic form, wherein the present investigation comprises the high silica zeolite in acidic form containing the oxides of group II, III, IV or VIII metals of the periodic table making the catalyst more active, selective and stable compared to the catalysts of the prior art. Secondly the reaction conditions specially the reaction temperature (350-450°C) is milder than the prior art processes. Thirdly the carbon deposition on catalyst surface during the reaction is comparatively very less and the catalyst can be regenerated calcining at lower temperature (500-550 C) within a short period (3-4 hrs. ) as compared to the prior art processes. The main object of the present investigation is to provide an improved process for the preparation of pyridine compounds which obviates the drawbacks of the hitherto known processes as detailed above. Another object of the present invention provides an improved process wherein an active, selective and stable catalyst is used for higher conversion to pyridine compounds. Accordingly, the present invention is to provides an improved process for the preparation of pyridine/substituted pyridine derivative which comprises heating acetaldehyde 25-29 wt%, formaldehyde 15-18 wt%, water 27-32 wt%, ammonia 18-21 wt% and methanol 0-15 wt% to a temperature in the range of 300-400°C, contacting the gaseous reactants so obtained with a zeolite based catalyst having silica to alumina ratio greater than 12 and containing 1 to 6% of mixture of oxides of metals of group II, III, IV or VIII of the periodic table at a temperature in the range of 350-500°C maintaining the contact time in the range of 0.5 to 5 seconds, collecting the resultant product and subjecting to extraction with an aprotic organic solvent by conventional methods such as herein described separating the organic layer by known methods to obtain pyridine/substituted pyridine derivative. The catalysts suitable for use in the process of this invention will generally have silica to alumina ratio in the range of 12-600. The catalysts having such low ;nount of aluminium are active ior the process of this invention as long as foregoing characteristics are met. Also suitabvle for use in the process of this invention will be the silica-poiyoaorph "silicalite" class of catalysts which have the properties required by this invention. The organic solvents used for extraction of the reaction products may be such as benzene, carbontetrachloride, carbondisulphide etc. Often the zeolites mentioned above will be prepared with or without organic cations. Zeolites prepared with organic cations will be inappropriate for use as such in this invesntion because they are catalytically inactive, presumably this is caused by the occupation of the intra crystalline free space by such cations. These catalysts can be activated by conventional heating to higher temperature in an inert atmosphere or vaccuum which results removal of such organic cations. Acidic form of zeolite are obtained by ion exchanging it with ammonium salt solution and then calcining the ammonium form of zeolite at higher temperature. The catalyst has been prepared by two methods (i) ion exchanging the ammonium form of zeolite by admixing with decomposable organic compound of the metal (ii) by impregnation method. Mixture of acetaldehyde and formaldehyde in the form of formalin (30-40% formaldehyde solution) are used as feed material. Fertilizer grade ammonia gas from ammonia gas cylinder is used. Acetaldehyde is obtained by the depolymerization of paraldehyde, a polymer of acetaldehyde. The vapours of acetaldehyde, aqueous formaldehyde solution and ammonia gas are activated in the preheating 2one of the reactor between 300-400°C and then finally heated over catalyst surface preferably at a temperature from 350-500 °C, a temperature from 400-500°C being particularly preferred. The invention may be carried out on a stainless steel fixed bed reactor. The catalyst is packed in the catalyst bed zone. The reactants are fed from top of the reactor by downward flow. Mixtures of acetaldehyde, formaldehyde (in the form of formalin) is kept in a glass/s.s well connected with a pumping out system. This is cooled by ice maintaining the temperature 3-5°C. Aldehyde mixture is fed in the reactor by precalibrated feeding pump namely prestaltic pump. Dry ammonia gas is fed to the reactor through a separate side tube of the reactor from ammonia gas cylinder measured by a precalibrated rotameter. Aldehyde vapour and ammonia gas are allowed to mix in the preheating zone. The reactor is mounted in a vertical tubular furnace having the temperature control and measuring devices. The temperature of the preheating zone is maintained between 300-400°C. The reaction is carried out in the temperature range of 400-500°C and contact time preferably between 1-5 seconds. The process of the present invention may also be carried out in a small glass/s.s. reactor using 15 ml/30 ml catalyst volume. The products are collected in two sets of condenser both cooled by ice. The outgoing gases are trapped first in saturated boric acid bubblers and then in a solution of 2,4-dinitrophenyl hydrazine to absorb unreacted ammonia and aldehydes respectively. The liquid product generally contains pyridine bases, water, unreacted ammonia, unreacted acetaldehyde and formaldehyde and some unidentified compounds. The liquid product is extracted with organic solvent such as bensene using 8% sodium chloride. The extraction is done to the extent of complete separation of organic part of the product from the aqueous part.Organic and aqueous layer both are analysed by gas chromatography. The organic layer may be also separated from aqueous layer by Dean and Start method of distillation. Individual pyridine compounds may be separated by fractional distillation of bensene extract containing organic layer. Further, the identity as well as the estimation of the individual bases namely pyridine, 2-picoline, 3-picoline, 4-picoline, lutidines and unreacted acetaldehyde, formaldehyde etc. may be confirmed by gas chromatography using Flame ionisation detector. In this investigation the gas chromatography column used was an s.s. 2M x 1/8" packed column containing polyethylene glycolsuccinate modified by Apiezon - L as stationary phase.The catalyst may be regenerated in a stream of air (60-90 ml/ gm cat/hr) heating at the temperature range 500-575 C for a period of 3-4 hrs. The product yield and ratio of pyridine to 3-picoline depends on the ratio of the feed materials as well as other reaction conditions.The maximum yield obtained during this investigation is 95 mole percent of total pyridine bases comprising 82.5% pyridine and 3-picoline. The weight ratio of pyridine to 3-picoline are generally in the range of 1.5 - 3.3 and mostly in the range of 1.5 - 2.5. The invention is illustrated by the examples given below which should not however, be construed to limit the scope of the present invention. Example 1 : 23 g(30 ml) catalyst I [ HZSM-5 (Si02:Al203 = 80) + ZnO] in the form of pellets (-6 + 14 BS mesh) was loaded in a tubular reactor (ID 18 mm) containing a thermowell of 7 mm (OD) and a free cross sectional area of 216 mm2 . The catalyst was purged under nitrogen gas at 450°C for 2 hrs. Ten experiments of two hours duration were performed at 450°C feeding the mixture of acetaldehyde and formaldehyde solution in water (31-37% formaldehyde) as well as ammonia gas separately into the reactor in the molar ratios of acetaldehyde : formaldehyde : water : ammonia (1:1:2.8:2.33). After each experiment, the catalyst was regenerated at 550°C in presence of air for 3 hrs. The average yield of pyridine bases obtained was 69.31 mole percent comprising 59.3 pyridine and 3- picoline. Example 2: The process of this invention was conducted in the same reactor as in example 1, loading 30 ml catalyst II [ HZSM-5 (SiO2:Al2O3 = 300) + ZnO ]. The feed materials - acetaldehyde, formaldehyde, water and ammonia gaas were fed into the reactor in molar ratios 1:1.5 : 4.2 : 3.92, maintaining the contact time at 1.2 secs and reaction temperature 475°C. ' Eight experiments of two hour's duration were made followed by regeneration in air at 550°C for 3 hrs. The experimental conditions and the results are shown below. (Table Removed) Example 3: Catalyst-III (15 ml) [ silicalite + ZnO) was loaded in the same reactor as in example I. The catalyst was activated at 450°C in a stream of nitrogen gas for 2 hrs. Then experiments were conducted by feeding the reactants in the molar ratio, acetaldehyde, formaldehyde - water - ammonia ( 1:0.5 - 1.5 : 2.5 - 4.2:1.26 5.21) preheated in the reactor between 300-400°C and finally the reaction takes place between 425 - 500°C. Fifteen runs were made using this catalyst in this reactor. The experiments were conducted for 2 hrs. and six hours followed by regeneration at 550°C for 3-4 hrs. in the presence of air. The experimental conditions and results are given below : (Table Removed) Example 4: In this invention the same catalyst was used as in example 3. The dimension of the fixed bed reactor was increased (I.D 21 mm and length 100 cm) and the volume of the catalyst was taken 100 ml (75 gm). The reaction conditions were maintained in the same fashion as in example 3. The catalyst bed height was 31 cm. In this reactor eight experimental runs were repeated under similar conditions. The percentage of yield obtained in this system was almost identical as it was obtained in the small reactor. (Table Removed) Example 5 23 g (30 ml) catalyst in the form of pellets (-6 + 14 BS mesh) was loaded in a tubulor reactor (ID 18 mm) containing a thermowell of 7 mm (OD) and a free cross sectional area of 216 mm2 . The catalyst was activated at 450°C in presence of air for 2 hrs. The experiments of two hour's duration were performed feeding the mixture of acetaldehyde and formaldehyde solution in water (31-37 % formaldehyde) as well as ammonia gas separately in the reactor in the molar ratios of acetaldehyde:formaldehyde:water:ammonia (1:1 : 2.8:2.33). Under these conditions the three catalysts including the commercial one were tested for their activities and the results are shown below: (Table Removed) This reveals the superiority of the catalyst investigated over commercial catalyst. Example 6 In this invention the catalyst III was modified (Catalyst-V) using 4% bentonite clay as binder. The reaction conditions and the results are shown below : (Table Removed) Example 7 Catalyst VI (15 ml) [ HZSM-5 (Si02 : A1203 = 400) + cobalt oxide + antimony oxide] was loaded in the same reactor as in example 2. The catalyst was activated at 450°C in a stream of air for two hrs. Eight experiments were conducted by feeding the reactants in the mole ratio 1:0.92:2.65:0.84:1.94 of acetaldehyde, formaldehyde, water, methanol and ammonia at reaction temperature 450°C. 88 mole% yield of total pyridine bases were obtained. (Table Removed) The main advantages of the improved process of the present invention are : (i) The catalyst is more active and selective towards the production of pyridine and 3-picoline resulting in high yields. (ii) The reaction products do not contain any 4-picoline (very negligible amount is present) as a result the isolation of the different reaction products in general and 3-picoline in particular is very easy. (iii) From purity point of view, the quality of pyridine and 3-picoline produced is acceptable for the preparation of pharmaceuticals. (iv) The carbon lay down on the catalyst surface is very low as compared to the art catalyst hitherto been employed in commercial practice. (v) It is possible to regenerate the catalyst at lower temperature (500-550°C) and in short period as compared to the commercial catalyst. We claim : 1. An improved process for the preparation of pyridine/substituted pyridine derivative which comprises heating acetaldehyde 25-29 wt%, formaldehyde 15-18 wt%, water 27-32 wt%, ammonia 18-21 wt% and methanol 0-15 wt% to a temperature in the range of 300-400°C, contacting the gaseous reactants so obtained with a zeolite based catalyst having silica to alumina ratio greater than 12 and containing 1 to 6% of mixture of oxides of metals of group II, III, iV or VIII of the periodic table at a temperature in the range of 350-500°C maintaining the contact time in the range of 0.5 to 5 seconds, collecting the resultant product and subjecting to extraction with an aprotic organic solvent by conventional methods such as herein described separating the organic layer by known methods to obtain pyridine/substituted pyhdine derivative. 2. An improved process as claimed in claim 1 wherein the zeolite based catalyst used has the ratio of SiO2 to AI2O3 in the range of 12 to 600. 3. An improved process as claimed in claims 1-2 wherein the aprotic organic solvent used for extraction of the mixed product is benzene, carbon tetrachloride, carbon disulphide. 4. An improved process for the preparation of pyridine/substituted pyridine derivative substantially as herein described with reference to the examples.

Documents:

684-del-1996-abstract.pdf

684-del-1996-claims.pdf

684-del-1996-complete specification (granted).pdf

684-del-1996-correspondence-others.pdf

684-del-1996-correspondence-po.pdf

684-del-1996-description (complete).pdf

684-del-1996-descripton (provisional).pdf

684-del-1996-form-1.pdf

684-del-1996-form-2.pdf

684-del-1996-form-3.pdf

684-del-1996-form-4.pdf

684-del-1996-form-6.pdf

684-del-1996-form-9.pdf