United States Patent (19) (11) 4,354,029 Kaiser et al. 45) Oct. 12, 1982 54) PREPARATION OF (56) References Cited 2-SUBSTITUTED-2-OXAZOLINES WITH ORGANIC ZINC SALT CATALYSTs U.S. PATENT DOCUMENTS 3,813,378, 5/1974 Whitte et al........................ 548/239 (75) Inventors: Mark E. Kaiser, Midland, Mich.; 3,917,631 11/1975 Arlt..................................... 548/239 David L. Larson, Cookeville, Tenn. 4,014,880, 3/1977, Dowd et al. ........................ 548/239 (73) Assignee: The Dow Chemical Company, 4,035,309 7/1977 Brois ................................... 548/239 Midland, Mich. FOREIGN PATENT DOCUMENTS (21) Appl. No.: 325,948 1483682 8/1977 United Kingdom . 22) Filed: Nov.30, 1981 Primary Examiner-Anton H. Sutto Related U.S. Application Data Attorney, Agent, or Firm-Charles J. Enright (6) Continuation of Ser. No. 966,696, Dec. 5, 1978, aban 57 ABSTRACT doned, which is a continuation-in-part of Ser. No. 2-Substituted-2-oxazolines are prepared by contacting 758,279, Jan. 10, 1977, abandoned, and Ser. No. N-(2-hydroxyalkyl)carboxamides with a small but cata 875,280, Feb. 6, 1978, abandoned. lytic amount of an organic zinc salt at an elevated tem (51) Int. Cl... CO7D 263/12 perature. (52) U.S.C. ........... (58). Field of Search......................................... 548/239. 8 Claims, No Drawings 4,354,029 1 2 . PREPARATION OF. SUMMARY OF THE INVENTION 2-SUBSTITUTED-2-OXAZOLNES WITH A new process for making 2-substituted-2-oxazolines ORGANICZNC SALT CATALYSTS has now been discovered. The new process comprises reacting by contacting in a liquid phase an N-(2-hydrox CROSS-REFERENCE TO RELATED yalkyl)carboxamide with a small but catalytic amount APPLICATIONS of an organic zinc salt. The temperature/pressure rela This application is a continuation of abandoned appli tionship is normally adjusted such that the oxazoline cation Ser. No. 966,696, filed Dec. 5, 1978, which is a and water codistill from the reaction mixture essentially continuation-in-part of abandoned application Ser. No. 0 as fast as they are formed. 758,279, filed Jan. 10, 1977, and copending application. DETAILED DESCRIPTION OF THE Ser. No. 875,280, filed Feb. 6, 1978, now abandoned. INVENTION BACKGROUND OF THE INVENTION The N-(3-hydroxyalkyl)carboxamides used in the 2-Substituted-2-oxazolines form a known class of 15 instant process are a known class of compounds which compounds having many members and many utilities. can be represented by the formula The chemistry of such oxazolines has been summarized, for example, by Wiley et al., Chemical Reviews, Vol. O 44, 447 (1949), by Seeliger et al., Angew. Chem. Inter national Edition, Vol. 5, No. 10, 875 (1966), and by 20 R-C-NH-CRR2-CRR-OH Frump, Chemical Reviews, Vol. 71, No. 5,483 (1971). wherein R is a hydrocarbon or an inertly-substituted Patents on monomeric oxazolines have been classified hydrocarbon group and R1-R4 are hydrogen or inert by the U.S. Patent and Trademark Office under organic radicals. By "inert" is meant inert in the instant 260/307F. - ... One of the prior art, processes for preparing 2-sub 25 process. Such carboxamides are typically prepared by stituted-2-oxazolines is the cyclodehydration of N-(p3 reacting a carboxylic acid (RC(OOH) or a lower alkyl hydroxyalkyl)carboxamides. This cyclodehydration ester of the carboxylic acid with an ethanolamine of the occurs in vapor. phase over alumina (U.S. Pat. No. iformula 3,562,263 and Frump vide supra, page 485) and in liquid phase over certain salts of manganese, cobalt, rare earth 30 NH2-CRR2-CR3R-OH (II) metals, molybdenum and tungsten (U.S. Pat. Nos. wherein. R1-R4 have the aforesaid meaning. The car 3,681,329 and 3,681,333). The latter two patents indicate boxylic acid/amine salt which is formed initially in that the cyclodehydration reaction is brought about by these reactions can be used in the instant process in heating the hydroxyamide and catalyst together in a place of the carboxamide. When such carboxylic acid distillation apparatus from which the oxazoline product 35 /amine salts are used, the carboxamide is generated in distills from the reaction mixture as it is formed along situ. In formulas I and II, R3 and R4 are each preferably with the by-product water. hydrogen and R1 and R2 are hydrogen, lower alkyl In another process, Ghera et al., J. Chem. Soc., Chem. (C1-C6), hydroxymethyl or alkanoyloxymethyl (al Commun, No. 11,639 (1972) teach that 2-substituted-2- kyl-C(O)-O-CH2-) groups of up to about 17 car oxazolines are prepared by heating N-(2-hydroxyalkyl)- bon atoms. More preferably, R1-R4 are each hydrogen. carboxamides in the presence of solid zinc acetate. Ex These preferences are based upon the commercial avail perimentally, the authors heated the carboxamide reac ability of the ethanolamines. Rin formula I is preferably tant with a ten-fold excess of powdered anhydrous zinc alkyl of from 1 to about 17 carbon atoms or phenyl and acetate in a glass tube under a constant flow of nitrogen is more preferably methyl, ethyl or phenyl and is most and atmospheric pressure. This resulted in a formation 45 preferably methyl or ethyl. Examples of suitable N-(3- of a 1:1 complex of oxazoline with zinc acetate which hydroxyalkyl)carboxamides include compounds of for was isolated. The complexes were subsequently decom mula I having the following values for R and R1-R4: TABLE I R R R2 R3 R4 H H H H C4H9 H H H C2H5 C2H5 H H H H H H CH2OH CH2OH. H. H CH2O(O)C-C17H35 H H H C6H5 H C6H5 H CH3 H H H CH3 CH3 H H CH3 H CH3 H H ; H . H H H H H H C6H5 H CH3 H H H CH3 CH3 CH3(CH2)CH-CH(CH2). H H H H cyclohexyl H H H. H and other like compounds. posed in a separate step into oxazolines by treatment The catalysts in the instant cyclodehydration reaction with water or filtration through a Florisil column. are organic zinc salts which are soluble in the carbox 4,354,029 3 4. amide reactant or liquid reaction medium. The term pure N-(3-hydroxyethyl)propionamide (290 g; 2.35 "soluble' is not meant to imply that the zinc salt is mole) was pumped in at approximately 0.9 g/min to the soluble or miscible in all proportions with the carbox system. As the propionamide was added to the reaction amide or liquid reaction medium but instead has at least mixture, a water-white distillate was collected overhead a minimum solubility (e.g., about 100 parts per million through the distillation apparatus at a head temperature or more) at reaction temperature. Such zinc salts are of 40° C.-45° C. After the addition of the propionamide used in the process in small but catalytic amounts. Nor was complete, the pot was heated to 220 C. to drive off mally, the zinc salts are charged in amounts of from the last amounts of 2-ethyl-2-oxazoline. The overhead about 0.005 to about 0.4 mole of zinc. salt per mole of distillate temperature. reached a maximum of 41 C. carboxamide reactant but more or less of the zinc salts 10 during this post-heating step. A total of 294.8g of wa can be used, if desired. Carboxylic acid salts of zinc ter-white distillate was thus obtained overhead leaving having the formula (RCOO-)22n++ wherein R is a 21.7 g of a tan, wet paste remaining in the pot. Analysis C1-C20 aliphatic or alicyclic radical or an inertly-sub of the distillate overheads by gas chromatography using stituted C1-C20 aliphatic or alicyclic carboxylic acid an internal standard and also a Karl Fischer water titra radical may be used as catalysts in the invention. Suit 15 able carboxylic acid zinc salts include, for example, zinc tion showed the material to be 2-ethyl-2-oxazoline, acetate, zinc formate, zinc propionate, zinc stearate, water and very minor amounts of unreacted propiona zinc neodecanoate, and the like. Zinc acetate is the mide and 2-methyl-2-oxazoline. The impurities in the current preferred catalyst. propionamide reactant were: water (approximately 1 The instant cyclodehydration reaction may be con percent); monoethanolamine (approximately 2-3 per ducted neat or in solution with a suitable inert solvent. cent); and the amidoester of propionic acid and mono By “inert' is meant inert in the process. Suitable such ethanolamine (approximately 1 percent). inert solvents include, for example, chlorinated hydro The oxazoline was produced in 96.2 percent yield, carbon solvents, aromatic hydrocarbons, cycloaliphatic based on the pure N-(3-hydroxyethyl)propionamide hydrocarbons, aliphatic hydrocarbons, and the like. We 25 charged to the system. The amount of water produced prefer, however, to conduct the reaction neat (i.e., that according to analysis was 93.0 percent of theory. The is without any solvent added). 2-ethyl-2-oxazoline can be easily separated from the The reaction temperature must, obviously, be suffi mixture by selective extraction using diethylbenzene cient to promote the cyclodehydration reaction and is followed by distillation. normally selected in the range of from about 140 C. to 30 about 280 C. Preferred reaction rates have been ob EXAMPLE 2 served at temperatures of from about 160 C. to about In another experiment, 2-ethyl-2-oxazoline was pre 250 C. The instant cyclodehydration reaction is also pared in 82 percent yield by warming a propionic acid preferably conducted under reduced pressure. This /ethanolamine salt in the presence of approximately 2 facilitates product recovery in that frequently a reaction mole percent zinc acetate dihydrate at a temperature of temperature may be chosen which is above the boiling 35 200 C./50 mm Hg.