Methods for synthesizing n-methylpiperazine diphenol amides and related compositions

Abstract

Methods for synthesizing N-methylpiperizinediphenol amide are provided. The methods include contacting a bisphenol acid with N-methylpiperizine to form a reaction mixture; and heating the reaction mixture to form a reaction product comprising N-methylpiperizinediphenol amide. Related compositions are also provided.

Description

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[0001] In general, the present invention relates to a method for synthesizing N-methylpiperazine diphenolamide. More specifically, the present invention relates to a method and related compositions for the one-step synthesis of N-methylpiperazine diphenolamide.

[0002] A typical method for synthesizing N-methylpiperazine diphenolamide involves a two-step reaction, which includes converting bisphenolic acid to a methyl bisphenolic acid ester, followed by the reaction of the ester with N-methylpiperazine. However, this method usually requires the addition of a solvent, making an additional solvent removal step necessary. Furthermore, this two-step method requires two separate steps to separate and purify the reaction products (methyl bisphenolic acid ester and N-methylpiperazine diphenolamide). Therefore, the typical two-step method may not provide the desired efficiency (yield) and may not be cost-effective.

[0003] Therefore, a cost-effective and efficient method for synthesizing N-methylpiperazine diphenolamide is needed. Furthermore, a one-step method for synthesizing N-methylpiperazine diphenolamide is also required. Invention Overview

[0004] Embodiments of the present invention are included to meet these and other needs. One embodiment is a method for synthesizing N-methylpiperazine diphenolamide. The method includes contacting bisphenolic acid with N-methylpiperazine to form a reaction mixture; and heating the reaction mixture to form a reaction product comprising N-methylpiperazine diphenolamide.

[0005] One embodiment is a method for synthesizing N-methylpiperazine diphenolamide. The method includes contacting bisphenolic acid with N-methylpiperazine under substantially solvent-free conditions to form a reaction mixture. The method further includes heating the reaction mixture at a temperature ranging from about 160°C to about 180°C for a duration ranging from about 16 hours to about 40 hours to form a reaction product comprising N-methylpiperazine diphenolamide.

[0006] One embodiment is a composition comprising N-methylpiperazine diphenolamide. The composition is formed by contacting bisphenolic acid with N-methylpiperazine to form a reaction mixture; and heating the reaction mixture to form a reaction product comprising N-methylpiperazine diphenolamide.

[0007] Detailed Explanation

[0008] The approximate language used throughout this specification and claims may be used to modify any quantitative expression that may vary within permissible limits without altering its essential function. Therefore, a value modified by one or more terms such as “about” and “substantially” is not limited to the specified precise value. In some cases, approximate language may correspond to the precision of the instrument used to measure the value. Unless otherwise indicated by context or language, scope limitations herein and throughout this specification and claims may be combined and / or interchanged, and such scope is defined to include all subscopes contained herein.

[0009] Unless the context clearly indicates otherwise, in the following description and claims, the singular forms “a” and “the” include the plural objects. Unless the context clearly indicates otherwise, the term “or” as used herein does not imply exclusivity and refers to the presence of at least one of the mentioned components and includes the possibility of combinations of the mentioned components.

[0010] A method for synthesizing N-methylpiperazine diphenolamide is provided. Specifically, a one-step method for synthesizing N-methylpiperazine diphenolamide is provided. As used herein, the term "one-step method" means the direct conversion of bisphenolic acid to N-methylpiperazine diphenolamide without additional intermediate steps to form an ester, as shown in Synthetic Scheme 1: .

[0011] This contrasts with the "two-step method" described in U.S. Patent No. 7,985,339, assigned to General Electric Company.

[0012] The method includes contacting bisphenol acid with N-methylpiperazine to form a reaction mixture. In some embodiments, the molar ratio of N-methylpiperazine to bisphenol acid is in the range of about 1.5 to about 5. In some embodiments, the molar ratio of N-methylpiperazine to bisphenol acid is in the range of about 3 to about 5. In some embodiments, the molar ratio of N-methylpiperazine to bisphenol acid is in the range of about 3 to about 4.

[0013] In some embodiments, bisphenolic acid is contacted with N-methylpiperazine under substantially solvent-free conditions. As used herein, the term "substantially solvent-free conditions" means that the amount of solvent added during the step of contacting bisphenolic acid with N-methylpiperazine is less than about 10% by weight of the total reaction mixture. In some embodiments, the reaction mixture is formed without adding any solvent to the mixture, and the reaction mixture may be completely solvent-free. In some embodiments, the reaction mixture may be in slurry form, formed by adding solid bisphenolic acid to a solution of N-methylpiperazine.

[0014] As previously suggested, in typical two-step methods, large amounts of solvent (e.g., methanol) are usually used during the step of converting bisphenolic acids to the corresponding esters, which requires additional solvent removal steps and can be costly. In contrast, according to some embodiments of the invention, the method eliminates the need for solvent addition and is therefore more cost-effective. Furthermore, the one-step method can be more efficient and provide higher yields when compared to two-step methods that require additional separation and purification steps.

[0015] The method further includes heating the reaction mixture to form a reaction product comprising N-methylpiperazine diphenolamide. In some embodiments, the method includes heating the reaction mixture at a temperature ranging from about 140°C to about 180°C for a duration ranging from about 8 hours to about 40 hours. In some embodiments, the method includes heating the reaction mixture at a temperature ranging from about 160°C to about 180°C for a duration ranging from about 16 hours to about 40 hours. In some embodiments, the reaction mixture may be heated gradually to the desired temperature over a period of time. In some embodiments, the reaction product may be in solution or slurry form.

[0016] The method further includes separating N-methylpiperazine diphenolamide from the reaction product. In some embodiments, N-methylpiperazine diphenolamide is separated from the reaction product by crystallization from a suitable solvent.

[0017] The reaction product may be substantially free of bisphenol A methyl ester. As used herein, the term "substantially free" means that the amount of bisphenol A methyl ester in the reaction product is less than 0.1% by weight. In some embodiments, the reaction product is completely free of bisphenol A methyl ester, that is, the amount of bisphenol A methyl ester in the reaction product is 0% by weight.

[0018] In some embodiments, the isolated N-methylpiperazine diphenol amide may have a purity greater than about 96%. In some embodiments, the isolated N-methylpiperazine diphenol amide may have a purity greater than about 98%. Furthermore, the yield of N-methylpiperazine diphenol amide relative to bisphenolic acid may be greater than about 80%. In some embodiments, the yield of N-methylpiperazine diphenol amide relative to bisphenolic acid may be greater than about 85%.

[0019] In some embodiments, a method for synthesizing N-methylpiperazine diphenolamide includes contacting bisphenolic acid with N-methylpiperazine under substantially solvent-free conditions to form a reaction mixture; and heating the reaction mixture at a temperature in the range of about 160°C to about 180°C for a duration in the range of about 16 hours to about 40 hours to form a reaction product comprising N-methylpiperazine diphenolamide.

[0020] Compositions comprising N-methylpiperazine diphenolamide are also provided. The compositions are formed by contacting bisphenolic acid with N-methylpiperazine to form a reaction mixture; and heating the reaction mixture to form a reaction product comprising N-methylpiperazine diphenolamide. As previously implied, in some embodiments, the compositions are substantially free of bisphenolic acid methyl esters. Furthermore, the N-methylpiperazine diphenolamide has a purity greater than about 98%. Example

[0021] Unless otherwise stated, chemicals are purchased from Aldrich and used as is.

[0022] Example 1: Preparation of N-methylpiperazine diphenolamide (N-MePip DP A) by a one-step method

[0023] 400 g (4.0 mol) of N-methylpiperazine was added to a 1.0 L three-necked flask equipped with a reflux condenser and a top-mounted mechanical stirrer. The resulting solution was stirred at room temperature under nitrogen. After 10 minutes, 286 g (1.00 mol) of bisphenol A as a solid was added to the solution to ensure no solid agglomeration and to obtain a homogeneous mixture. The resulting slurry was heated in an external oil bath at 160 °C. During heating, the slurry became a clear solution, which began to reprecipitate (ammonium salt formation) when the oil temperature approached 80 °C. As the oil temperature continued to rise to 110 °C, the reaction mixture became a thick paste, which gradually thinned and remelted when the oil bath temperature approached 160 °C. The temperature was maintained at 160 °C for 8 hours, during which time the reaction mixture became a clear, amber liquid. In addition, the inner tank temperature was increased from 125 °C to 136 °C during this time. After 8 hours, the oil temperature was gradually increased to 180°C and maintained at this temperature until all starting materials were consumed (approximately another 8-16 hours). Excess N-methylpiperazine was allowed to be distilled off during the reaction (approximately 15 grams of N-methylpiperazine was distilled off completely). It was confirmed that distillation of no more than 20 grams was acceptable, otherwise there was a risk of crystallization upon cooling. During the reaction, the tank temperature was increased from 125°C to 148°C.

[0024] After completion (as determined by HPLC), the mixture was cooled to approximately 110°C (internal temperature), and 1.0 L of water was slowly added to maintain the solution. Initially, for the first 100 mL of water added, water was added at a rate of 2.0 mL / min, during which time the amber solution became less viscous and further precipitation of a white solid began (internal temperature dropped to approximately 86°C). The remaining water was added over 1 hour (at a rate of 15 mL / min). After all the water had been added, the temperature was allowed to cool to room temperature, resulting in a slurry containing a white precipitate. The precipitate was obtained by filtration to obtain a grayish-white solid. The crude solid was dried under vacuum for 24 hours by gradually heating from 50°C to 80°C (95% separation yield, approximately 99% purity).

[0025] The resulting dried solid was dissolved in hot ethanol (1.0 L), and 500 mL of water was slowly added while maintaining the temperature at 80 °C. After all the water was added, the heating was removed, and the solution was allowed to cool to room temperature and stirred for another 12 hours. The recrystallized product was separated by filtration and dried under vacuum at 50 °C–80 °C for 24 hours. 312.8 g of a pure white solid with a purity greater than 99% was obtained in 85% yield, with a melting point of 196–197 °C.

[0026] Comparative Example 1: Preparation of N-methylpiperazine diphenolamide (N-MePip DPA) via a two-step method

[0027] N-methylpiperazine diphenolamide was also synthesized from the corresponding methyl esters using a two-step method, as described in U.S. Patent No. 7,985,339, assigned to General Electric Company. This two-step method yields a crude material with a separation yield of 80-85% by precipitation with an acetone-water mixture. Therefore, the overall crude yield from this two-step method is less than the crude yield from the one-step method described in Example 1.

[0028] The appended claims are intended to protect the invention with the breadth of scope already conceived, and the embodiments provided herein describe selected embodiments by illustrating all possible implementations in various forms. Therefore, the applicant intends that the appended claims are not limited to the selection of embodiments used to illustrate the features of the invention. The word “comprising” as used in the claims and its grammatical variations logically also include and encompass phrases of varying degrees and variations, such as, but not limited to, “consistently consisting of” and “consisting of”. Scopes have been provided where necessary; those scopes include all subscopes therein. It should be anticipated that variations within these scopes are self-evident to those skilled in the art, and that, without being disclosed to the public, such variations should be considered to be covered by the appended claims where possible. Advances in science and technology are also anticipated to enable equivalents and substitutes that are not currently conceivable due to linguistic imprecision, and these variations should also be considered to be covered by the appended claims where possible.

Claims

1. A method for synthesizing N-methylpiperazine diphenolamide, comprising: Bisphenolic acid is contacted with N-methylpiperazine under solvent-free conditions to form a reaction mixture; and the reaction mixture is heated at a temperature in the range of 140°C to 180°C for a duration in the range of 8 to 40 hours to form a reaction product comprising N-methylpiperazine diphenol amide, wherein the N-methylpiperazine diphenol amide has a purity greater than 98%, and wherein the molar ratio of N-methylpiperazine to bisphenolic acid is in the range of 3 to 4.

2. The method of claim 1, comprising heating the reaction mixture at a temperature in the range of 160°C to 180°C for a duration in the range of 16 hours to 24 hours.

3. The method of claim 1, further comprising separating N-methylpiperazine diphenolamide from the reaction product by crystallization.

4. The method of claim 1, wherein the reaction product is free of bisphenol A methyl ester.

5. The method of claim 1, wherein the yield of N-methylpiperazine diphenol amide relative to bisphenolic acid is greater than 80%.

6. A method for synthesizing N-methylpiperazine diphenolamide, comprising: Bisphenolic acid is contacted with N-methylpiperazine under solvent-free conditions to form a reaction mixture; and The reaction mixture is heated at a temperature ranging from 160°C to 180°C for a duration ranging from 16 hours to 24 hours to form a reaction product comprising N-methylpiperazine diphenol amide. The molar ratio of N-methylpiperazine to bisphenol A is in the range of 3-4.