Title of Invention

A PROCESS OF PREPARATION OF A CONDENSATION PRODUCT

Abstract

The present invention provides a process of preparation of a condensation product, such as herein described, which comprises : (a) preparing a sodium C 4- C8 alkoxide by treating a stirred dispersion of sodium metal in a solvent in the manner such as herein described, optionally under an inert atmosphere with a less than stoichiometric amount of C4 - C8 alkanol at a temperature of——100°C to 140°C to form a mixture comprising a first phase and a second phase, wherein the first phase comprises a solution of the sodium C4 - C8 alkoxide in the solvent and the second phase comprises the sodium metal, separating in the manner such as herein described, the first phase to obtain the product sodium C4 - C8 alkoxide as the solution, and optionally continuously recycling the remaining mixture; and (b) subjecting one or more condensable organic compounds, such as 4- chloro -3', 4'-dimethoxy benzophenone and acetyl morpholine, to base-catalysed condensation in the presence of a catalyst, sodium C4-C8 alkoxide prepared according to step (a).

Full Text

-2- The present invention relates to a process for the preparation of condensation product using sodium C4 - C8 alkoxide This application is divided out of Indian Patent Application No. 1001/CAL/96 (hereinafter referred to as the "parent application"). Sodium C4-C8alkoxides are important, versatile chemicals useful in a wide variety of synthetic reactions and manufacturing procedures wherein a strong organic base is desired. Although the formation of a sodium C4-C8alkoxide by the reaction of sodium metal and a C4-C8 alkanol is well-known, in actual practice, the reaction on a large scale may be hazardous and costly. In many processes, the addition of a catalyst is required or energy intensive reaction conditions, such as high temperature (>160°C) and high pressure, are required. -3- According to the parent application there is provided a process for the manufacture of sodium C4 - C8 alkoxide-which comprises treating a stirred dispersion of sodium metal in a solvent, in the manner such as herein described, optionally under an inert atmosphere with a less than stoichiometric amount of C4 - C8 alkanol at a temperature of about 100°C to 140°C to form a mixture comprising a first phase and a second phase, wherein the first phase comprises a solution of the sodium C4 - C8 alkoxide in the solvent and the second phase comprises the sodium metal, separating, in the manner such as herein described, the first phase to obtain the product sodium C4 - C8 alkoxide as the solution, and optionally continuously recycling the remaining mixture. The invention of the parent application provides a safe, efficient and essentially quantitative process for the manufacture of sodium C4-C8alkoxide which comprises treating a stirred dispersion of sodium metal in a solvent optionally under an inert atmosphere with a less than stoichiometric amount of a C4-C8alkanol at a temperature of 110°-14 0°C to form a two phase mixture and separating the top phase to obtain the product sodium C4 -C8alkoxide as a solvent solution, optionally continuously recycling the remaining phase mixture. The sodium C4-C8alkoxide solution, thus obtained, may be used as a manufacturing intermediate and directly integrated into an existing manufacturing process stream or, alternatively, the solution may be cooled and filtered to give a pure crystalline sodium C4-C8alkoxide product suitable for storage and shipping. The production and handling of sodium C4-C8alkoxides are frequently costly and hazardous, particularly sodium tertiary-alkoxides, such as sodium t-butoxide. Even so such strong organic bases are commonly used in synthetic reactions and manufacturing processes. -4- It has now been found that sodium C4-C8alkoxide may be prepared safely and effectively on a large manufacturing scale with essentially quantitative conversion of the C4-C8 alkanol and optionally the continuous recycle of the unreacted sodium metal. Accordingly, sodium metal is dispersed in a solvent, preferably an aromatic hydrocarbon or mixture thereof having a boiling point greater than 100°C, optionally under an inert atmosphere, at about 100° to 140°C, preferably about 120° to 130°C. A less than stoichiometric amount of a C4-C8alkanol, preferably about 0.1 to 0.9 molar equivalents, more preferably about 0.4 to 0.6 molar equivalents, alone or in combination with a solvent, preferably an aromatic hydrocarbon or mixture thereof, is added to the heated dispersion with rapid stirring to form a two phase reaction mixture. Said reaction mixture is held without stirring at about 10 0° to 140°C, preferably at about 120° to 130°C, until the phase separation is complete. The top phase is removed by decantation to give a solvent solution of the product sodium C4-C8alkoxide. Optionally, the remaining phase mixture may be cooled to room temperature, treated with additional sodium metal and solvent, heated to about 10 0° to 140°, preferably 120° to 130°C, optionally under an inert atmosphere with rapid stirring to form a dispersion and treated with a less than stoichiometric amount of a C4-C8 alkanol as described hereinabove to produce a sol-vent solution of the product sodium C4-C8alkoxide and a phase mixture containing unreacted sodium metal. Said solvent solution of sodium C4-C8alkoxide may be removed by decantation and said phase mixture containing unreacted sodium may be continuously recycled in the above manner. The inventive process is illustrated in Flow Diagram I -5- wherein x and y are molar equivalents of Na and C4-C8 alcohol, respectively, and y Since y is always less than x, i.e. less than a stoichiometric amount, the starting C4-C8alkanol is essentially quantitatively converted to the product sodium C4-C8alkoxide. Further, since the unreacted sodium is continuously recycled, the inventive process is essentially waste free and, therefore, highly environmentally desirable. Moreover, the inventive process allows for relatively mild reaction conditions, atmospheric pressure, lower reaction temperatures and shorter reaction times which result in high throughput and high productivity without the loss of safety or the burden of hazardous or toxic waste. Among solvents suitable for use in the process of the invention are aromatic hydrocarbons or mixtures thereof having a boiling point greater than about 100°C, such as xylene, toluene, xylidene, cumene or the like, either alone or in combination. All C4-C8alkanols are suitable for use in the process of the invention, particularly branched alkanols such as t-butanol or t-amyl alcohol, more particularly t-butanol . -6- Although the inventive process of the parent application may be carried out in the presence of air, the introduction of an inert atmosphere such as nitrogen, helium, argon or the like, preferably nitrogeni greatly enhances the safe handling of the hydrogen gas which is produced during the reaction. In one embodiment of the invention according to the parent application, the product sodium C4-C8 alkoxide solvent solution may be integrated directly into an existing manufacturing process stream, such that a continuous production of a solvent solution of a strong organic base is supplied to a manufcturing scale reaction such as a base condensation or Knoevenagel reaction. In another embodiment of the invention according to the parent application, the product sodium C4-C8 alkoxide solvent solution may be cooled and filtered to give an essentially pure crystalline sodium C4-C8 alkoxide product suitable for storage and shipping and as a resource for a high quality, reagent grade, organic base. For a more clear understanding of the aforesaid invention, specific examples are set forth below. These examples are merely illustrative and are not to be understood as limiting the scope and underlying principles of the invention in any way. Indeed, various modifications of the invention, in addition to those shown and described herein, will become apparent to those skilled in the art. Such modifications are also intended to fall within the scope of the appended claims. -7- EXAMPLE 1 Continuous Production Of Sodium t-Butoxide As A 17% wt/wt Solution A mixture of sodium metal (87.6 g, 3.81 mole) in 752g of CYCLOSOL®53, a solvent consisting of a mixture of aromatic hydrocarbons manufactured by Shell Oil Company, Houston, Texas, in a 1. 5L double wall reactor with four baffles and a double 4-bladed skew propeller is blanketed with nitrogen and heated to 125°C. - At 125°-13O°C, the mixture is stirred rapidly to disperse the molten sodium metal and 5g of a 1:1 mixture of t-butanol and CYCLOSOL®53 (2.5g, 0.03 mole t-butanol) is added to initiate the reaction. The remaining t-butanol is added over a 3 hour period as a 1:1 mixture with CYLCOSOL®53 (277.3g, 1.87 mole t-butanol) at 13O°C. The resultant mixture is held at 13O°C with no stirring for 0.25 hours to separate the phases. A portion of the top phase (670.9g) is separated by decantation to give a 17% wt/wt solution of sodium t-butoxide in CYCLOSOL®53 . The remaining phase mixture consisting of a sodium t-butoxide solution in CYCLOSOL®53 (415.7g) and molten sodium metal (44g, 1.91 mole) is cooled to room temperature. This cooled phase mixture is treated with a second mixture of fresh sodium metal (26.3g, 1.14 mole) and 452g of CYCLOSOL®53, blanketed with nitrogen and heated to 125°C. At 125-130°C, the reaction mixture is stirred rapidly to disperse the molten sodium metal. The heated, stirred reaction mixture is treated with 169.6g of a 1:1 mixture of t-butanol and CYCLOSOL®53 (1.14 mole t-butanol) over a 1.5 hour period at 125°-130°C. The resultant two phase mixture is held with no stirring at 13O°C for 0.25 hours. A 640.2g portion of the top phase is separated by decantation to give a 17% wt/wt -8- solution of sodium t-butoxide f 1 .13 mole sodium t -but oxide) in CYCLOSOL®53. The remaining phase mixture of 411.7g of a solution of sodium t-butoxide in CYCLOSOL 53 and 44g of molten sodium (1.91 mole) is cooled to room temperature. The above procedure is then repeated to give a continuous production of sodium t-butoxide as a 17% wt/wt solution in CYCLOSOL®53. EXAMPLE 2 Continuous Production Of Sodium t-Butoxide As A Solid A mixture of sodium metal (77.3kg, 3.36 kmole) in 668kg of CYCLOSOL®53 in a reactor fitted with baffles and a propeller is blanketed with nitrogen and heated to 120°-13 0°C. The heated mixture is rapidly stirred to finely disperse the molten sodium metal and a 1:1 mixture of t-butanol and CYCLOSOL®53 (3.9kg, 0.026 kmole of t-butanol) is added to initiate reaction. The remaining t-butanol is added as a 1:1 mixture with CYCLOSOL®53 (245.1kg, 1.65 kmole of t-butanol) at 13 0°C over a 1.5 hour period. The resultant two phase reaction mixture is held at 130°C with no stirring for about 1 hour. A portion of the top phase (570kg) is removed and cooled to about 20°C. The resultant white crystalline precipitate is filtered. The filtercake is washed with about 10L of isohexane and dried at 30°C/400mBar to give the title product as a white solid, 96kg (1.0 kmole), 99-100% purity. The mother liquor and isohexane washings containing sodium t-butoxide (0.65 kmole) in CYCLOSOL®53 are combined, recycled to the original reactor containing the remaining reaction phase mixture and heated to 135°C to remove the isohexane. The resultant remaining reaction phase mixture is then included in a subsequent 1.0 kmolar reaction process as described hereinabove. -9- The present invention provides a process of preparation of a condensation product, such as herein described, which comprises : (a) preparing a sodium C4 - C8 alkoxide by treating a stirred dispersion of sodium metal in a solvent in the manner such as herein described, optionally under an inert atmosphere with a less than stoichiometric amount of C4 - C8 alkanol at a temperature of 100°C to 140°C to form a mixture comprising a first phase and a second phase, wherein the first phase comprises a solution of the sodium C4 - C8 alkoxide in the solvent and the second phase comprises the sodium metal, separating in the manner such as herein described, the first phase to obtain the product sodium C4 - C8 alkoxide as the solution, and optionally continuously recycling the remaining mixture; and (b) subjecting one or more condensable organic compounds, such as 4- chloro -3', 4'-dimethoxy benzophenone and acetyl morpholine, to base-catalysed condensation in the presence of a catalyst, sodium C4-C8 alkoxide prepared according to step (a). Condensation reactions for this purpose include, for example, the Michael reaction, Cannizzaro reaction and aldol condensations and condensation products may be Michael, Cannizzaro or aldol condensation product. One example is the process disclosed in EP 0 329 256 B, -10-WE CLAIM. 1. A process of preparation of a condensation product, such as herein described, which comprises : -(a) preparing a sodium C4 - C8 alkoxide by treating a stirred dispersion of sodium metal in a solvent in the manner such as herein described, optionally under an inert atmosphere with a less than stoichiometric amount of C4 - C8 alkanol at a temperature of 100°C to 140°C to form a mixture comprising a first phase and a second phase, wherein the first phase comprises a solution of the sodium C4 - C8 alkoxide in the solvent and the second phase comprises the sodium metal, separating in the manner such as herein described, the first phase to obtain the product sodium C4 - C8 alkoxide as the solution, and optionally continuously recycling the remaining mixture; and -(b) subjecting one or more condensable organic compounds, such as 4- chloro -3', 4'-dimethoxy benzophenone and acetyl morpholine, to base-catalysed condensation in the presence of a catalyst, sodium C4-C8 alkoxide prepared according to step (a). 2. A process as claimed in claim 1, wherein the solvent used in step (a) is an aromatic hydrocarbon or a mixture of aromatic hydrocarbons. 3. A process as claimed in claim 1 or 2, wherein the process of step (a) is carried out under inert atmosphere. 4. A process as claimed in claim 3, wherein the inert atmosphere is nitrogen. 5. A process as claimed in any of claims 1 to 4, wherein the amount of C4 - C8 alkanol used in step (a) is about 0.10 to 0.90 molar equivalents. 6. A process as claimed in claim 5, wherein the amount of C4 - C8 alkanol used in step (a) is about 0.4 to 0.6 molar. -11- 7. A process as claimed in any one of claims 1 to 6, wherein the remaining phase mixture in step (a) is continuously recycled. 8. A process as claimed in any one of claims 1 to 7, wherein the temperature adopted in step (a) is ——120° to 130° C. 9. A process as claimed in any one of claims 1 to 8, wherein the C4 - C8 alkanol used in step (a) is a tertiary C4 - C8 alkanol. 10. A process as claimed in claim 9, wherein the tertiary C4 - C8 alkanol is t-butanol or t-amyl alcohol. 11. A process as claimed in claim 10, wherein the tertiary C4 - C8 alkanol is t-butanol. 12. A process as claimed in claim 6 wherein the C4 - C8 alkanol is t- butanol and the temperature is 120° - 130° C. 13. A process as claimed in any one of claims 1 to 12, wherein the first phase of the mixture formed in step (a) is cooled after separation and filtered to yield the sodium C4 - C8 alkoxide as a solid. 14. A process for the preparation of a condensation product, substantially as herein described, particularly with reference to any of the foregoing examples. The present invention provides a process of preparation of a condensation product, such as herein described, which comprises : (a) preparing a sodium C 4- C8 alkoxide by treating a stirred dispersion of sodium metal in a solvent in the manner such as herein described, optionally under an inert atmosphere with a less than stoichiometric amount of C4 - C8 alkanol at a temperature of——100°C to 140°C to form a mixture comprising a first phase and a second phase, wherein the first phase comprises a solution of the sodium C4 - C8 alkoxide in the solvent and the second phase comprises the sodium metal, separating in the manner such as herein described, the first phase to obtain the product sodium C4 - C8 alkoxide as the solution, and optionally continuously recycling the remaining mixture; and (b) subjecting one or more condensable organic compounds, such as 4- chloro -3', 4'-dimethoxy benzophenone and acetyl morpholine, to base-catalysed condensation in the presence of a catalyst, sodium C4-C8 alkoxide prepared according to step (a).

Documents:

00640-cal-2002 abstract.pdf

00640-cal-2002 assignment.pdf

00640-cal-2002 claims.pdf

00640-cal-2002 correspondence.pdf

00640-cal-2002 description (complete).pdf

00640-cal-2002 form-1.pdf

00640-cal-2002 form-18.pdf

00640-cal-2002 form-2.pdf

00640-cal-2002 form-3.pdf

00640-cal-2002 letters patent.pdf

00640-cal-2002 p.a.pdf

00640-cal-2002 priority document.pdf

00640-cal-2002 reply f.e.r.pdf

640-CAL-2002-CORRESPONDENCE_1.1.pdf

640-CAL-2002-FORM 27_.pdf

640-CAL-2002-FORM-27-1.1.pdf

640-CAL-2002-FORM-27.pdf