Title of Invention

"GREEN CATALYTIC PROCESS FOR ASPIRIN SYNTHESIS USING FLY ASH AS HETEROGENEOUS SOLID ACID CATALYST"

Abstract

This invention relates to a catalytic process for the preparation of acetyl salicylic acid, Aspirin using nano-crystalline activated fly ash solid acid catalyst having crystallite size in the range of 13-28 nm,BET surface area in the range of 80-120m2g-1" pore volume 0.08-0.2 cm3g-1" pore size 35-60 A° comprising of Chemical activation of raw fly ash with sulfuric acid (with different fly ash/sulfuric acid ratio) at boiling temperature; Ageing the slurry at 110°C for 5 days under stirring afterwards refluxing the slurry at 110°C for 4h,Washing the slurry with water and drying at 110°C for 24 h followed by calcinations at temperature 600°C for 4 h, reacting salicylic acid with acetic anhydride in presence of fly ash catalyst in a solvent free medium, maintaining the substrate to catalyst ratio 5-20 weight percent; maintaining the temperature of the reaction in the range of 90 to 120° at atmospheric pressure for a period selected from 30 to 120 min; separating the product aspirin (acetyl salicylic acid) from the reaction mixture by known filtration techniques; washing the catalyst with acetone to remove adhering materials and drying the catalyst at 110°C followed by air calcinations at 450°C for a period between 2-4h.

Full Text

Green Catalytic process for aspirin synthesis using fly ash as heterogeneous solid acid catalyst. Field of invention This invention relates to the development of a new process for the synthesis of aspirin from solid acid catalyst prepared from flyash. Background of the invention Existing process of the synthesis of acetyl salicylic acid is an acid catalyzed esterification reaction by the acetylation of the salicylic acid with acetic anhydride using conventional liquid acids, namely, cone. Fb 864 or cone. HaPC^ at the temperature of 80-90°C. The reaction mixture is cooled in ice bath followed by addition of chilled water in the reaction mixture to hydrolyze unreacted acetic anhydride to acetic acid. The reaction mixture is kept for crystallization of acetyl salicylic acid. The crystals are separated by vacuum filtration and recrystallized by toluene as solvent. These processes have the drawbacks in terms of using corrosive, hazardous mineral acids, which involve post reaction work-up for the disposal of spent acid. The drawback of the synthesis is the use of water-soluble homogeneous acids, which cannot be recovered, and results in acid waste effluent and results in low yield. Furthermore, gummy polymeric byproduct formed during the synthesis needs to be removed and the crude product is also required to be purified by the treatment with saturated sodium bicarbonate leading to increase in unit-operation to obtain the final product. Toluene is also not a good solvent used for re-crystallization as it releases volatile organic vapors into the atmosphere. The existing process for the synthesis of acetyl salicylic acid is beset with serious drawbacks. For example, the use of hazardous mineral acids is not safe from handling point of view, as these are corrosive and irritant; difficult to separate after the reaction and therefore encounters the problem of spent acid disposal. Furthermore, to recover and crystallize the crude aspirin product from the reaction mixture is also a time consuming tedious process during re-crystallization of acetyl salicylic acid from water, usually in trace amount but sometimes it is also formed in large quantity, and needs to be removed by filtering the hot aqueous solution and thus making crystallization process tedious and results into acetyl salicylic acid crystals of low purity. Therefore, methodology to develop a solid acid from fly ash a novel method for the utilization of solid waste fly ash and to synthesize acetyl salicylic acid from fly ash catalyst to overcome the above mentioned disadvantages. The prepared catalyst is an eco-friendly and safer catalyst with high yield of acetyl salicylic acid crystals of high purity. Activated fly ash catalyst is proved to be the best solution for the above-mentioned problems. To overcome the difficulties of homogeneous mineral acid, few strong solid acids viz sulfated zirconia; sulfated titania, zeolites, acidified clays etc. Can be used. But inventor's catalysts is quite cost effective as fly is an abundant waste of power plants; inventors have converted this waste into an effective solid acid. i Objects of the Invention The main object of this invention is to develop a new process for the synthesis of aspirin. Other object is to utilize waste flyash in aspirin synthesis through a green route. Another object of the invention is to synthesize nano-crystalline solid acid catalyst from raw fly ash with higher silica content, generated from thermal power plant. Another object of the present invention is to synthesize solid acid catalyst by chemical activation followed by drying at drying at 110°C and calcinations at higher temperature. Yet another object of the present invention is to synthesize nano-crystalline activated fly ash from raw fly ash by activation technique to increase silica content and BET surface area of the activated fly ash. Still another object of the present invention is to synthesize aspirin usin nano-crystalline activated fly ash as solid acid catalyst. Yet another object of the present invention is one pot synthesis of aspirin in a single step, solvent free environment at atmospheric pressure and moderate temperature. STATEMENT OF INVENTION According to this invention there is provided a catalytic process for the preparationof acetyl salicylic acid, Aspirin using nano-crystalline activated flyash solid acid catalyst having: - (i)crystallite size in the range of 13-28 nm (ii)BET surface area in the range of 80- 120m2g-1. (iii)pore volume 0.08-0.2 cm3g-1 (iv)pore size 35-60 A° comprising of :- (i) Chemical activation of raw fly ash with sulfuric acid (with different fly ash/sulfuric acid ratio) at boiling temperature; (ii) Ageing the slurry at 110°C for 5 days under stirring afterwards refluxing the slurry at 110°C for 4h. (iii) Washing the slurry with water and drying at 110°C for 24 h followed by calcination at temperature 600°C for 4 h. (iv) reacting salicylic acid with acetic anhydride in presence of fly ash catalyst in a solvent free medium, maintaining the substrate to catalyst ratio 5-20 weight percent; (v) maintaining the temperature of the reaction in the range of 90 to 120° at atmospheric pressure for a period selected from 30 to 120 min; (vi) separating the product aspirin (acetyl salicylic acid) from the reaction mixture by known filtration techniques; (vii) washing the catalyst with acetone to remove adhering materials and (viii) drying the catalyst at 110°C followed by air calcination at 450°C for a period between 2-4h. Detailed description of Invention The present invention provides a novel method for the synthesis of an eco-friendly green solid acid catalyst from solid waste fly ash and the use of the activated fly ash catalyst in solvent free green synthesis of acetyl salicylic acid by O-acetylation of salicylic acid with acetic anhydride to replace the conventional homogenous liquid cid catalysts viz sulfuric acid and phosphoric acid. Nano-crystalline activated fly ash was prepared by activation fly ash collected from Kota super Thermal Power Station. The fly ash was characterized to determine its chemical composition, activity and reactivity. It was activated both chemically and thermally for making a catalyst. Chemical activation was done by acid leaching of fly ash, which was carried out in a stirred reactor taking Fly ash and concentrated H4SO4 acid in different ratios ranging from 3:1 to 1:2 designated as FA-1, FA-2, FA-3 and FA-4. The mixture was heated at 110°C and aged for 5 days maintaining the temperature. After ageing the dark pulp obtained was further refluxed at boiling temperature 110°C for 4h and then washed with distilled water and dried at 110°C for 24h followed by calcinations at 600°C for 4 hours in flow air. Structural characterization of all above prepared catalysts was done by FT-IR Spectroscopy and X-ray powder diffraction techniques. The crystallite size was determined from XRD data. BET surface area was measured by N2 adsorption-desorption isothem study at 77.4 K. The bulk sulfur content in the activated fly ash samples were measured by elemental analysis. The prepared samples had crystallite size ranging from 28-12 am as determined from X-ray diffraction. Sulfur loaded on the catalysts as measured by elemental analysis were in the range of 0.5-1.0 wt%, silica content of the samples ranges from 71-86% and BET surface area was in the range of 80-120 m2/g. The characteristics of nano-crystalline fly ash prepared with varied parameters along are summarized in Table 1. The synthesis of acetyl salicylic acid was carried out using nano-crystalline activated fly ash as catalyst in liquid phase in a 50 ml round bottom flak equipped with magnetic stirrer at one atmosphere. The optimization of reaction parameters for the synthesis of the acetyl salicylic acid was carried out with nano-crystalline fly ash catalyst (FA-4). In a typical procedure, the salicylic acid and acetic anhydride were heated in a 50ml round bottom flask at the temperature ranging from 90 to 120°C for 30 to 120 minutes. The synthesis of the acetyl salicylic acid was carried out with molar ratio of salicylic acid to acetic anhydride 1:4. The synthesis of the acetyl salicylic acid was carried out with varied salicylic acid to fly ash catalyst weight ratio ranging from 5 to 20 under similar reaction condition and at atmospheric pressure. Table 1. Characterization of activated fly ash used for the synthesis of acetyl salicylic acid. (Table Removed) FA; fly ash The synthesis of acetyl salicylic acid was carried out from 1 to 10 g scale of salicylic acid under the similar reaction conditions resulting similar yield of acetyl salicylic with no side products. Separation of acetyl salicylic acid from the reaction mixture was done by adding chilled water to hydrolyze unreacted acetic anhydride to acetic acid and to crystallize acetyl salicylic acid crystals from the reaction mixture at atmospheric temperature and pressure followed by filtration and re-crystallization using ethanol-water system. The product (crude and re-crystallized) obtained was of high purity as confirmed by melting point (133-135°C), FT-IR, andNMR Spectroscopy. The recovered nano-crystalline fly ash catalyst, after filtration from reaction mixture, was thermally regenerated at 450°C for 2-4 h in air. The regenerated catalyst was used for further reaction cycles up to tow cycles without loss of activity and resulting similar yield as fresh catalyst and the product obtained was of high purity as before, as confirmed by melting point, FT-IR, and NMR Spectroscopy. Acetylsalicylic acid (Aspirin): White solid, mp 133-135 °C, (lit. mp 135°C); FTIR (KBr) v = 1754, 1690 cm'1; 'H NMR, 8H (200MHZ, CDCI3); 2.36 (s, 3H), 7.15 (d, 1H), 7.38 (t,l H),7.63(t, 1H), 8.13(d, 1H). The yield of the acetyl salicylic acid was calculated as: The investigated esterification is a Bronsted acid catalyzed reaction; the mechanistic path of the reaction involves involves the generation of acyl carbonium ion electrophile from acetic anhydride in presence of an acid catalyst, which attacks on phenolic oxygen of salicylic acid to form acetyl salicylic acid. Nano-crystalline size of the catalyst provides large fraction of active species on the surface thus enhancing the catalytic activity of the catalyst. The drug with high selectivity and yield in accordance with the invention can be synthesized in a solvent free environment using easily separable catalyst. Interestingly the catalyst can be regenerated for further use. The hitherto known process does not divulge nor teach how solid acid catalyst can be used for the synthesis of acetyl salicylic acid at atmospheric pressure. It is reported for the first time in the present invention how the a solid waste raw fly ash can be converted into an efficient solid acid catalyst by activation technique which enhance the silica surface hydroxyl group and BET surface area to great extent thus increasing the catalytic activity of the catalyst. The -catalytic conversion of salicylic acid to acetyl salicylic acid can be achieved in presence of this solid acid catalyst generated from fly ash, in solvent free environment. The inventive steps adopted in the present invention are (i) conversion of fly ash into solid acid catalyst by activation method decreases the cost of catalyst and makes the process more cost effective; (ii) the catalytic conversion take place in solvent free environment. This dispenses the need of the use of any solvent; (ii) soild acid catalyst can be easily recovered and reused. It alleviates the problem of separating homogeneous catalyst from the reaction product; (iii) the catalytic conversion is achieved in benign condition liquid acid catalyst; (iv) the process does not involve any post reaction workup for the disposal of corrosive and hazardous spent acid; (v) catalyst is developed from fly ash which is a solid waste this process finds an effective and novel use of fly ash; (vi) the process is cost effective lowering the cost of catalyst as well as product upto reasonable extent. The main advantages of this process of this process over conventional process include: 1. The present process employs use of fly ash ( a solid waste) in the synthesis of solid acid catalysts by activation technique. 2. The activated fly ash catalyst prepared from fly ash is ecofriendly and cost effective. 3. An introduction o new class of solid acid catalyst from waste is a novel use of fly ash thus reducing the solid waste which is of great environmental concern. 4. Catalyst being solid in nature can be easily separated from the liquid reaction mixture by means of filtration or centrifugation 5. The present process employs activated fly ash as solid acid catalyst, which is environment friendly, safe in handling and do not generate any waste or by product. 6. The reaction process is a single step process without use of any solvent. 7. Furthermore, this process is carried at moderate conditions of pressure and temperature. 8. Catalysts being highly crystalline and thermally stable can be regenerated by thermal treatment and can be re-used. 9. Activated fly as as solid acid catalysts are easy in transforming, handling etc. in comparison to conventional catalysts like HaSC^, CtbCOOH, and BF3.OEt2. EXAMPLE- 1 The characterized fly ash from Kota Super Thermal Power Station, was activated both chemically followed by thermal treatment. Chemical activation was done by concentrated sulfuric acid, which wash carried out in a stirred reactor taking Fly ash and concentrated H2SO4 acid in different ratio ranging from 3:1 to 1:2 designated as FA-1, FA-2, FA-3 and FA-4 respectively. The mixtures were heated at 110 °C and aged for 5 days maintaining the temperature. After ageing the dark pulp obtained was further refluxed at boiling temperature 1 10 °C for 4h and then samples were washed with distilled water and dried at 1 10 °C for 24h followed by calcinations at 600 °C for 4 hours in flow air. EXAMPLE- 2 0.0072 moles of salicylic acid and 0.029 moles acetic anhydride (molar ratio= 1:4) were taken in a 50 ml round bottom flask immersed in oil bath maintained at 120 °C. Nano-crystalline fly ash catalyst (FA-1, FA-2, FA-3, FA-4), activated at 450 °C in static air with salicylic acid to catalyst weight ratio 10:1, were added and the mixtures were heated at 120 °C for 30 minutes. The reaction mixtures were filtered to separate the catalyst. The acetyl salicylic acid was crystallized from the reaction mixture. The crude yield of acetyl salicylic acid obtained with catalysts FA-1, FA-2, FA-3, FA-4 were 75, 79, 87, 97 % respectively. Crude acetylsalicylic acid obtained was further re-crystallized with ethanol-water to obtain pure crystals of acetyl salicylic acid and was characterized by melting point, FT-IR, and NMR spectroscopy. EXAMPLE-3 0.0072 moles of salicylic acid and 0.029 moles acetic anhydride (molar ratio=l:4) were taken in a 50 ml round bottom flask. Nano=crystalline fly ash catalyst (FA-4), activated at 450°C in static air with salicylic acid to catalyst weight ratio 10:1, was added and the mixtures were heated at 90 °C for 30, 60 and 120 minutes. The reaction mixtures were filtered to separate the catalyst. The acetyl salicylic acid was crystallized from the reaction mixture. The crude yields of acetyl salicylic acid obtained at 30, 60 and 120 minutes were 68, 76 and 77 % respectively. Crude acetylsalicylic acid obtained was further re-crystallized with ethanol-water to obtain pure crystals of acetyl salicylic acid and was characterized by melting point, FT-IR, and NMR spectroscopy. EXAMPLE-4 0.0072 moles of salicylic acid and 0.029 moles acetic anhydride (molar ratio=l:4) were taken in a 50 ml round bottom flask. Nano-crystalline fly ash catalyst (FA-4), activated at 450 °C in static air with salicylic acid to catalyst weight ratio 10:1, was added and the mixtures were heated at 100 °C for 30, 60 and 120 minutes. The reaction mixtures were filtered to separate the catalyst. The acetyl salicylic acid was crystallized from the reaction mixture. The crude yields of acetyl salicylic acid obtained at 30, 60 and 120 minutes were 78, 82 and 81 % respectively. Crude acetylsalicylic acid obtained was further re-crystallized with ethanol-water to obtained was further re-crystallized with ethanol-water to obtain pure crystals of acetyl salicylic acid and was characterized by melting point, FT-IR, and NMR spectroscopy. EXAMPLE-5 0.0072 moles of salicylic acid and 0.029 moles acetic anhydride (molar ratio = 1:4) were taken in a 50 ml round bottom flask. Nano-crystalline fly ash catalyst (FA-4), activated at 450 °C in static air with salicylic acid to catalyst weight ratio 10:1, was added and the mixtures were heated at 120 °C for 30, 60 and 120 minutes. The reaction mixtures were filtered to separate the catalyst. The acetyl salicylic acid was crystallized from the reaction mixture. The crude yields of acetyl salicylic acid obtained at 30, 60 and 120 minutes were 97, 96 and 94 % respectively. Crude acetylsalicylic acid obtained was further re-crystallized with ethanol- water to obtain pure crystals of acetyl salicylic acid and was characterized by melting point, FT-IR, NMR spectroscopy EXAMPLE-6 0.0072 moles of salicylic acid and 0.029 moles acetic anhydride (molar ratio = 1:4) were taken in a 50 ml round bottom flask. Nano-crystalline fly ash catalyst (FA-4), activated at 450°C in static air with different salicylic acid to catalyst weight ratio 20:1, 10:1 and 5:1 were added and the mixtures were heated at 120°C for 30 minutes. The reaction mixtures were filtered to separate the catalyst. The acetyl salicylic acid was crystallized from te reaction mixture. The crude yields of acetyl salicylic acid with different substrate to catalyst weight ratio 20:1, 10:1 and 5:1 was 87, 97 and 97%. Crude acetylsalicylic acid obtained was further re-crystallized with ethanol-water to obtain pure crystals of acetyl salicylic acid and was characterized by melting point, FT-IR, and NMR spectroscopy EXAMPLE-7 The recovered FA-4 catalyst, after filtration from the reaction in example 5, was thermally regenerated at 450°C for 2 h in static air. The reaction on the regenerated catalyst was carried out under similar reaction conditions i.e. by taking 0.0072 moles of salicylic acid and 0.0029 moles acetic anhydride (molar ratio of 1:4), in a 50 ml round bottom flask equipped with magnetic stirrer. Regenerated FA-4 catalyst was added in th reaction mixture with salicylic acid to catalyst weight ratio 10:1 and the mixture was heated at 120°C for 30 minutes. The reaction mixture was filtered to separate the catalyst. The acetyl salicylic acid was crystallized from the reaction mixture. The catalyst was recovered and used after regeneration for further three reaction cycles. The crude yield of acetyl salicylic acid was in range of 89-97%. It is to be noted that the present invention is susceptible to modifications, adaptations and changes by those skilled in the art. Such variant embodiments employing the concepts and features of this invention are intended to be within the scope of the present invention, which is further set forth under the following claims:- We claim; 1. A catalytic process for the preparation of acetyl salicylic acid, Aspirin using nano-crystalline activated fly ash solid acid catalyst having: -(i) crystallite size in the range of 13-28 nm (ii) BET surface area in the range of 80-120m2g-1-(iii) pore volume 0.08-0.2 cm3g-1 (iv) pore size 35-60 A° comprising of :- (i) Chemical activation of raw fly ash with sulfuric acid (with different fly ash/sulfuric acid ratio) at boiling temperature; (ii) Ageing the slurry at 110°C for 5 days under stirring afterwards refluxing the slurry at 110°C for 4h. (iii) Washing the slurry with water and drying at 110°C for 24 h followed by calcination at temperature 600°C for 4 h. (iv) reacting salicylic acid with acetic anhydride in presence of fly ash catalyst in a solvent free medium, maintaining the substrate to catalyst ratio 5-20 weight percent; (v) maintaining the temperature of the reaction in the range of 90 to 120° at atmospheric pressure for a period selected from 30 to 120 min; (vi) separating the product aspirin (acetyl salicylic acid) from the reaction mixture by known filtration techniques; (vii) washing the catalyst with acetone to remove adhering materials and (viii) drying the catalyst at 110°C followed by air calcination at 450°C for a period between 2-4h. 2. A catalytic process as claimed in claim 1, wherein the esterificationof salicylic acid with acetic anhydride is carried out in a single step without the use of any solvent. 3. A catalytic process as claimed in claim 1, wherein the nano- crystalline activated fly ash catalyst having sulfur content in the range of 0.5 to 1.0 weight percent after calcination at 600°C. 4. A catalytic process as claimed in claim 1, wherein silica content of nano crystalline activated fly ash catalyst is in the range 71-86% after chemical and thermal activation. 5. A catalytic process as claimed in claim 1, wherein the esterification is carried out at temperature maintained between 90 to 120°C atatmospheric pressure, without generating any hazardous by product. 6. A catalytic process as claimed in claim 1, wherein the catalyst is separated from the reaction mixture regenerated by washing with acetone and heating in air at 450°C for a period in the range 2-4h. 7. A catalytic process as claimed in claim 1, wherein the crude acetyl salicylic acid is crystallized from the reaction mixture and recrystalized with ethanol water mixture to obtain pure crystals. 8. A catalytic process as claimed in claim 1, wherein the catalyst can be easily separated and regenerated for reuse.

Documents:

1980-del-2007-Abstract-(04-02-2013).pdf

1980-del-2007-abstract.pdf

1980-del-2007-Claims-(04-02-2013).pdf

1980-del-2007-claims.pdf

1980-del-2007-Correspondence Others-(22-04-2013).pdf

1980-del-2007-correspondence others-(28-04-2008).pdf

1980-del-2007-Correspondence-Others-(04-02-2013).pdf

1980-DEL-2007-Correspondence-Others.pdf

1980-del-2007-description (complete).pdf

1980-del-2007-drawings.pdf

1980-del-2007-form-1.pdf

1980-del-2007-form-18-(28-04-2008).pdf

1980-del-2007-form-2.pdf

1980-del-2007-gpa.pdf

1980-del-2007-Petition-137-(04-02-2013).pdf