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United States Patent (19) 11 4,347,379 Lai 45) Aug United States Patent (19) 11 4,347,379 Lai 45) Aug. 31, 1982 54 SYNTHESIS OF 57 ABSTRACT ALPHA-ALKOXYCARBOXYLIC ACDS Numerous alpha-carboxylic acids are prepared in a 75 Inventor; John T. Lai, Broadview Heights, liquid medium by the reaction of an organic compound Ohio having at least one reactive hydroxyl or thiol group, with a monoketone, and a haloform, in the presence of 73 Assignee: The B. F. Goodrich Company, Akron, a phase transfer catalyst and an alkali metal hydroxide. Ohio The term "alpha-alkoxycarboxylic acids' includes al pha-phenoxycarboxylic acids, alpha-thioalkoxycar (21) Appl. No.: 129,000 boxylic acids and alpha-thiophenoxycarboxylic acids. 22 Filed: Mar. 10, 1980 Specific substituents on the beta carbon atom of an 51 int. C. .............................................. C07C 51/00 alpha-alkoxycarboxylic (or "2-alkoxycarboxylic') acid 52 U.S. C. .................................... 562/495; 564/189; reaction product formed in this novel synthesis, are 564/201; 260/399; 564/202; 564/205; introduced by appropriate choice of the ketone reac 260/405.5; 564/209;564/210; 260/413; tant; alkoxy and phenoxy substituents on the alpha car 260/465 D; 260/465.4; 562/426; 562/431; bon atom of a 2-alkoxycarboxylic acid are introduced 562/468; 562/470,562/471; 562/472; 562/500; by appropriate choice of the organic compound having 562/504:562/505; 562/507; 562/508; 562/510; a hydroxyl or thiol group. De-alkoxylation of the 2 562/581; 562/586; 562/587; 562/588; 562/599; alkoxycarboxylic acid yields alpha-beta monoolefini 564/123; 564/161; 564/162; 564/171; 564/174; cally unsaturated carboxylic acids which are necessarily 564/175; 564/181; 564/188: 564/191 alpha substituted, and may also be beta-substituted. It is 58) Field of Search ............... 562/470,588, 471, 431, now possible to produce, simply and conveniently, 562/508, 512, 426, 472, 468, 505, 507,581,586, numerous substituted alpha-beta monolefinically unsat 587, 602,495, 500, 504,510,599; 260/399, 413, urated carboxylic acids with a variety of substituents on 465.4, 465 D, 405.5 the alpha carbon atom, and, optionally on the beta car bon atom of these substituted carboxylic acids. Esters 56) References Cited may also be conventionally derived from both the 2 U.S. PATENT DOCUMENTS alkoxycarboxylic acids, and the unsaturated carboxylic acids. 2,490, 109 12/1949 Weizmann .......................... 562/588 2,525,249 10/1950 Weizmann ... ... 562/588 During the phase transfer catalyzed synthesis of this 3,038,002 6/1962 Reeve.............. ... 562/470 invention, an intermediate acyl halide derivative is 3,368,943 2/1968 Gilbert et al. ... ... 562/588 formed prior to the formation of the 2-alkoxycarboxylic 3,992,432 11/1976 Napier et al. .................... 260/465.1 acid reaction product. The formation of the acyl halide 4,167,512 9/1979 Lai ................................ 260/239.3 B derivative allows the subsequent direct formation, in a modification of the same reaction, of 2-alkoxycarboxy OTHER PUBLICATIONS lic acid amides (or "2-alkoxycarbamides'), simply by Weizmann et al., J.A.C.S. 70, pp. 1153-1157, (1948). adding a primary or secondary amine to the reaction Starks, Chemtech, Feb. 1980, pp. 110-117, (1980). mass. By dealkoxylation of the 2-alkoxycarbamides, Weygand, Preparative Organic Chemistry, pp. 868-871, specific, necessarily alpha-substituted and optionally (1972). beta-substituted acrylamides are synthesized which pre Primary Examiner-Michael L. Shippen viously could be prepared, if at all, only with difficulty. Attorney, Agent, or Firm-Alfred D. Lobo: Nestor W. Shust 7 Claims, No Drawings 4,347,379 2 monoxide, phosgene and formic acid. It is the difficulty SYNTHESIS OF ALPHA-ALKOXYCARBOXYLC of preparing alpha-trichloromethyl alkanol which limits ACDS the applicability of the disclosed Weizmann et al reac tion to alpha-isobutyric acid. Yet the preparation of the BACKGROUND OF THE INVENTION s TCMA is critical because the disclosed reaction will not This invention is related to a novel synthesis of alpha proceed if acetone and chloroform are substituted for alkoxycarboxylic acids which, with known technology, the TCMA. It is the difficulty of making and using could otherwise only be made in the laboratory, usually TCMA which limits its use in the disclosed synthesis to with considerable difficulty. By the term "alpha-alkox the laboratory. ycarboxylic acids' I refer also to alpha-phenoxycar- O A phase transfer catalyzed reaction known as the boxylic acids, alpha-thioalkoxycarboxylic acids, and "ketoform reaction' is disclosed in my U.S. Pat. No. alpha-thiophenoxycarboxylic acids. This invention is 4,167,512, and illustrated in one particular example by more particularly related to the preparation of beta-sub the reaction of a N,N'-alkyl substituted ethylene di stituted alpha-alkoxycarboxylic acids from which can amine with acetone and chloroform; and, in another be derived a wide variety of (a) substituted acrylic acids example, with o-phenylene diamine reacted with cyclo which are both alpha and beta substituted, and (b) sub hexanone and chloroform. The reaction product in each stituted acrylamides which are both alpha and beta example is a 2-keto-1,4-diazacycloalkane. The patented substituted. The alpha-alkoxycarboxylic (or "2-alkoxycarboxy synthesis also proceeds by virtue of a phase transfer lic") acids and their esters have been highly regarded 20. catalyzed reaction mechanism in which an amine, a for their utility in perfumes and other cosmetics; paints, haloform and a ketone are separate reactants, but the coatings and impregnants; texties; and, in the paper patented synthesis does not envision the use, as yet industry. The acids and esters have also been used on a another reactant, of an organic compound having at laboratory scale, as a starting material for the prepara least one reactive hydroxyl or thiol group. tion of various acrylates some of which, if they were 25 SUMMARY OF THE INVENTION commercially available, could provide polymers with a wide range of physical and chemical properties not It has been discovered that an organic compound readily available in available acrylates and methacry having at least one reactive hydroxyl or thiol group, lates. As is well known, the physical and chemical prop such as alcohols and thioalcohols, phenols and thio erties of polymers of acrylic acid esters and methacrylic 30 phenols will react in a phase transfer catalyzed reaction acid esters depend to a large degree on the type of with a haloform, and a ketone, to yield alpha-alkoxycar alcohol from which the esters are prepared, and, the boxylic acids. More particularly, the alpha-alkoxycar length of the sidechain. Little is known about the prop boxylic acids may be produced with a wide variety of erties of acrylates with substituents on the beta carbon, substituents, both on the alpha and the beta carbon simply because making compounds with such substitu- 35 atoms, under controlled easily obtained conditions, ents was impractical. Still less is known about polymers usually without requiring heating of the reaction mix which may be formed from substituted acrylic acids ture. having substituents on both the alpha and beta carbon Accordingly, it is a general object of this invention to atOS. provide a simple and convenient synthesis of alpha Thus, despite the ability of acrylate and methacrylate 40 alkoxycarboxylic acids including alpha-phenoxycar esters to copolymerize with nearly all types of mono boxylic acids, and corresponding thioalkoxy carboxylic mers, which ability has resulted in extensive industrial acids, utilizing commercially available raw materials, use of the esters, the fact remains that, because of the unavailability of all but a few acrylate and methacrylate which react in the presence of a phase transfer catalyst, esters, only the few are presently in wide use. This is so 45 and provide excellent yields with a remarkable freedom despite the knowledge that some polymers which have from undesirable byproducts. more desirable properties for specific applications than It is also a general object of this invention to provide poly(methyl methacrylate) ("PMMA') or copolymers alpha-alkoxycarboxylic acids which may thereafter be of methyl methacrylate and other esters may even be de-alkoxylated to alpha-beta monoolefinically unsatu more economical than PMMA. It is undisputed that the 50 rated carboxylic acids which are necessarily alpha-sub bulk availability of only a few substituted acrylates has stituted and optionally, also beta-substituted, and which precluded the commercial exploitation of many novel acids would otherwise be impractical to synthesize. acrylate-containing polymers, particularly those acryl It is a specific object of this invention to provide a ates with substituents on both the alpha and beta carbon novel synthesis, wherein a preselected primary or sec atoms. 55 ondary alcohol or thioalcohol, phenol or thiophenol, is In an article titled "The Synthesis of alpha-Alkox reacted with a saturated acyclic or cyclic monoketone, yisobutyric Acids and Alkyl Methacrylates from and, a haloform, in the presence of (i) a phase transfer Acetonechloroform', by Ch. Weizmann, M. Sulz catalyst (ii) an organic solvent, and (iii) solid or aqueous bacher and E. Bergman, J.A.C.S. Vol 70, p. 1153-1157, alkali. The phase transfer catalyst is selected from the there is disclosed a preparation starting with alpha-tri- 60 group consisting of a tertiary or quaternary compound chloromethyl alkanol (referred to in the article as of an element selected
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