Process for producing 1,3-oxazolidine derivatives

Abstract: A process produces 1,3-oxazolidine derivatives by reacting an imine derivative of the following formula (1): with an epoxy compound of the following formula (2): to yield an oxazolidine derivative of the following formula (3): A compound of Group 3 elements of the Periodic Table of Elements, or other metallic compounds can be used as a catalyst. In the formulae, R 1 , R 2 , R 4 , R 5 , R 6 , and R 7 are each, independently, a hydrogen atom, a hydrocarbon group, or a heterocyclic group, and R 3 is a hydrogen atom, a hydrocarbon group, a heterocyclic group, a hydroxyl group, a substituted oxy group, or an amino group which may have a substituent, where a combination of R 1 and R 2 , R 4 and R 5 , R 6 and R 7 , or R 4 and R 6 may be combined to form a ring with the adjacent carbon atom or carbon-carbon bond. The process can easily yield 1,3-oxazolidine derivatives from readily available materials.

Description: The present invention relates to a process for poducing 1,3-oxazolidine derivatives, which are useful as, for example, pharmaceuticals, agrochemicals, and other fine chemicals or intermediates thereof. As examples of production processes for 1,3-oxazolidine derivatives, a process of reacting a β-aminoalcohol derivative with an aldehyde, and a process of reacting an ethyleneimine derivative with an aldehyde are known. These processes, however, require β-aminoalcohol derivatives or ethyleneimine derivatives as materials which may not be significantly available, and therefore are not always satisfactory for general purpose use and are insufficient in yields. Processes for the preparation of 1,3-oxazolidine derivatives comprising reacting an imine derivative with an epoxy compound in the presence of a metallic compound catalyst (SnCl 4 ) are known from the following publications: CHEMICAL ABSTRACTS, vol. 76, no. 9, February 28, 1972, Columbus, Ohio, US; abstract no. 46128v, HAYASHI S. et al., "Reactions of epoxides. II. Synthesis of oxazolidines by the reaction of epoxide with Schiff bases", page 371; XP002137260 & CHEM. PHARM. BULL., vol. 19, no. 11, 1971, pages 2404-9; ODA R. et al., "New addition reactions. II. Addition of aliphatic epoxides to Schiff bases", BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, vol. 35, no. 7, July 1962, pages 1216-8, XP002137257; and BULATOVA O.F. et al., "Synthesis of substituted 5-chloromethyl-1,3-oxazolidines", RUSSIAN JOURNAL OF ORGANIC CHEMISTRY, vol. 30, no. 1, June 10, 1994, pages 58-61, XP002137258. It is an object of the present invention to provide a process capable of easily obtaining 1,3-oxazolidine derivatives from readily available materials. It is another object of the invention to provide a process for producing 1,3-oxazolidine derivatives, which process is satisfactory for general purpose use. A further object of the invention is to provide a process for obtaining 1,3-oxazolidine derivatives in good yields. After intensive investigations to achieve the above objects, the present inventors found that a reaction between an imine derivative and an epoxy compound in the presence of a specific catalyst can efficiently yield a corresponding 1,3-oxazolidine derivative. The invention has been accomplished on the basis of the above findings. Specifically, the invention provides, in an aspect, a process for producing 1,3-oxazolidine derivatives, said process comprising: reacting an imine derivative of the following formula (1): wherein R 1 and R 2 are each, identical to or different from each other, a hydrogen atom; an aliphatic hydrocarbon group selected from C 1-10 alkyl groups, C 2-10 alkenyl groups and C 2-10 alkynyl groups, an alicyclic hydrocarbon group selected from 3 to 12-membered cycloalkyl groups and 3 to 12-membered cycloalkenyl groups, a C 6-10 aromatic hydrocarbon group, or a group formed from these groups combined together; or a heterocyclic group selected from 5-membered rings, 6-membered rings and condensed rings each containing a hetero atom selected from oxygen, sulfur and nitrogen; R 3 is a hydrogen atom; an aliphatic hydrocarbon group selected from C 1-10 alkyl groups, C 2-10 alkenyl groups and C 2-10 alkynyl groups, an alicyclic hydrocarbon group selected from 3 to 12-membered cycloalkyl groups and 3 to 12-membered cycloalkenyl groups, a C 6-10 aromatic hydrocarbon group, or a group formed from these groups combined together, a heterocyclic group selected from 5-membered rings, 6-membered rings and condensed rings each containing a hetero atom selected from oxygen, sulfur and nitrogen, a hydroxyl group; a substituted oxy group, said oxy group being selected from C 1-10 alkoxy groups, aryloxy groups and aralkyloxy groups; an amino group, a mono- or di-C 1-6 alkylamino group or a cyclic amino group; where R 1 and R 2 may be combined to form a ring with the adjacent carbon atom, said ring being selected from 3 to 20-membered non-aromatic carbocyclic rings and non-aromatic heterocyclic rings; with an epoxy compound of the following formula (2): wherein R 4 , R 5 , R 6 , and R 7 are each, identical to or different from one another, a hydrogen atom; an aliphatic hydrocarbon group selected from C 1-10 alkyl groups, C 2-10 alkenyl groups and C 2-10 alkynyl groups, an alicyclic hydrocarbon group selected from 3 to 12-membered cycloalkyl groups and 3 to 12-membered cycloalkenyl groups, a C 6-10 aromatic hydrocarbon group, or a group formed from these groups combined together; or a heterocyclic group selected from 5-membered rings, 6-membered rings and condensed rings each containing a hetero atom selected from oxygen, sulfur and nitrogen; where each combination of R 4 and R 5 , R 6 and R 7 , or R 4 and R 6 may be combined to form a ring with the adjacent carbon atom or the adjacent carbon-carbon bond, said ring being selected from 3 to 20-membered non-aromatic carbocyclic rings and non-aromatic heterocyclic rings; to yield an oxazolidine derivative of the following formula (3): wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 have the same meanings as defined above; and wherein the reaction is performed in the presence of a metallic compound catalyst comprising a compound of Group 3 or 4 element of the Periodic Table of Elements. According to a preferred embodiment of the invention said metallic compound catalyst is a compound of a Group 3 element of the Periodic Table of Elements. The term "imine derivative" as used herein means and includes not only imine compounds in a narrow meaning but also oximes, oxime ethers, hydrazone derivatives, and other various compounds each having a C=N bond. The aliphatic hydrocarbon groups represented by R 1 , R 2 and R 3 in formula (1) include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-bucyl, pentyl, hexyl, decyl, and other alkyl groups each having 1 to 10 (preferably 1 to 6, and more preferably 1 to 4) carbon atoms; vinyl, allyl, 1-butenyl, and other alkenyl groups each having 2 to 10 (preferably 2 to 6, and more preferably 2 to 4) carbon atoms; ethynyl, propynyl, and other alkynyl groups each having 2 to 10 (preferably 2 to 6, and more preferably 2 to 4) carbon atoms. The alicyclic hydrocarbon groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl, and other cycloalkyl groups each having 3 to 12 (preferably 3 to 8, and more preferably 5 or 6) members; cyclopentenyl, cyclohexenyl, and other cycloalkenyl groups each having 3 to 12 (preferably 3 to 8, and more preferably 5 or 6) members. Examples of the aromatic hydrocarbon groups are phenyl and naphthyl groups. Hydrocarbon groups formed from an aliphatic hydrocarbon group and an alicyclic hydrocarbon group combined together include, but are not limited to, cyclopentylmethyl, cyclohexylmethyl, 2-cyclohexylethyl, and other C 3 -C 12 cycloalkyl-C 1 -C 4 alkyl groups, and other cycloalkyl-alkyl groups. Examples of hydrocarbon groups formed from an aliphatic hydrocarbon group and an aromatic hydrocarbon group combined together are C 7 -C 14 aralkyl groups, and other aralkyl groups; and a phenyl group substituted with one to four C 1 -C 4 alkyl groups, and other alkylsubstituted aryl groups. Preferred hydrocarbon groups include C 1 -C 10 alkyl groups, C 2 -C 10 alkenyl groups, C 2 -C 10 alkynyl groups, C 6 -C 10 aromatic hydrocarbon groups, C 3 -C 12 cycloalkyl-C 1 -C 4 alkyl groups, and C 7 -C 14 aralkyl groups. The hydrocarbon groups may have a variety of substituents, such as a halogen atom, an oxo group, a hydroxyl group, substituted oxy groups (e.g., alkoxy groups, aryloxy groups, aralkyloxy groups, and acyloxy groups), a carboxyl group, substituted oxycarbonyl groups, substituted or unsubstituted carbamoyl groups, a cyano group, a nitro group, substituted or unsubstituted amino groups, and heterocyclic groups. Heterocyclic rings to constitute the heterocyclic group in R 1 , R 2 , and R 3 include aromatic heterocyclic rings and non-aromatic heterocyclic rings. Such heterocyclic rings include heterocyclic rings each having an oxygen atom as a hetero atom, heterocyclic rings each having a sulfur atom as a hetero atom, and heterocyclic rings each having a nitrogen atom as a hetero atom. Examples of the oxygen-containing heterocyclic rings are furan, tetrahydrofuran, oxazole, isoxazole, and other 5-membered rings; 4-oxo-4H-pyran, tetrahydropyran, morpholine, and other 6-membered rings; and benzofuran, isobenzofuran, 4-oxo-4H-chromene, chroman, isochroman, and other condensed rings. The sulfur-containing heterocyclic rings include, but are not limited to, thiophene, thiazole, isothiazole, thiadiazole, and other 5-membered rings; 4-oxo-4H-thiopyran, and other 6-membered rings; and benzothiophene and other condensed rings. Examples of the nitrogen-containing heterocyclic rings include pyrrole, pyrrolidine, pyrazole, imidazole, triazole, and other 5-membered rings; pyridine, pyridazine, pyrimidine, pyrazine, piperidine, piperazine, and other 6-membered rings; and indole, indoline, quinoline, acridine, naphthyridine, quinazoline, purine, and other condensed rings. The heterocyclic rings may each have a substituent. Such substituents include, for example, those as exemplified in the description of the hydrocarbon groups, alkyl groups (e.g., methyl, ethyl, and other C 1 -C 4 alkyl groups), cycloalkyl groups, and aryl groups (e.g., phenyl and naphthyl groups). As rings formed by R 1 and R 2 combined together with the adjacent carbon atom, there may be mentioned cyclobutane, cyclopentane, cyclohexane, cyclohexene, cyclooctane, cyclododecane, and other non-aromatic carbocyclic rings (cycloalkane rings and cycloalkene rings) and non-aromatic heterocyclic rings each having 3 to 20 (preferably 3 to 15, and more preferably 5 to 12) members. These rings may have any of the aforementioned substituents, and to these rings, another ring (a non-aromatic or aromatic ring) may be condensed. The substituted oxy groups in R 3 include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutyloxy, and other C 1 -C 10 alkoxy groups (preferably, C 1 -C 6 alkoxy groups); phenoxy group, and other aryloxy groups; and benzyloxy, 2-phenylethyloxy, and other aralkyloxy groups. Examples of the amino group which may have a substituent in R 3 include amino group; methylamino, dimethylamino, ethylamino, diethylamino, propylamino and other mono- or di-C 1 -C 6 alkylamino groups ; and 1-pyrrolidinyl, piperidino, morpholino, and other cyclic amino groups. Preferred examples of R 1 and R 2 include a hydrogen atom, C 1 -C 10 alkyl groups, C 2 -C 10 alkenyl groups, C 2 -C 10 alkynyl groups, C 6 -C 10 aromatic hydrocarbon groups, C 3 -C 12 cycloalkyl-C 1 -C 4 alkyl groups, and C 7 -C 14 aralkyl groups. Alternately, R 1 and R 2 may be preferably combined with the adjacent carbon atom to form a non-aromatic carbocyclic ring having 3 to 15 members. Preferred examples of R 3 are C 1 -C 10 alkyl groups, C 2 -C 10 alkenyl groups, C 2 -C 10 alkynyl groups, C 6 -C 10 aromatic hydrocarbon groups, C 3 -C 12 cycloalkyl-C 1 -C 4 alkyl groups, and C 7 -C 14 aralkyl groups. The imine derivatives of the formula (1) may be either ketimines in which both R 1 and R 2 are not hydrogen atoms, or aldimines in which at least one of R 1 and R 2 is a hydrogen atom. Typical examples of the imine derivatives of the formula (1) include N-ethylidenemethylamine, N-ethylidenebenzylamine, N-ethylidenecyclohexylamine, N-ethylideneaniline, N-isopropylidenebutylamine, N-isopropylidenebenzylamine, N-isopropylidenecyclohexylamine, N-isopropylideneaniline, N-butylidenebutylamine, N-(1-methylbutylidene)butylamine, N-(1-etylpropylidene)butylamine, N-cyclohexylidenebutylamine, N-cyclohexylidenebenzylamine, and N-benzylideneethylamine. The imine derivatives of the formula (1) can be obtained by the dehydration condensation of corresponding carbonyl compounds (R 1 R 2 C=O) with corresponding amines (R 3 NH 2 ), where necessary in the presence of an acid. [Epoxy Compound] In the formula (2), the hydrocarbon groups and the heterocyclic groups in R 4 , R 5 , R 6 , and R 7 respectively include those exemplified as the hydrocarbon groups and heterocyclic groups in the substituents R 1 and R 2 . These hydrocarbon groups and heterocyclic groups may have any of the aforementioned substituents. Preferred hydrocarbon groups include C 1 -C 10 alkyl groups, C 2 -C 10 alkenyl groups, C 2 -C 10 alkynyl groups, C 6 -C 10 aromatic hydrocarbon groups, C 3 -C 12 cycloalkyl-C 1 -C 4 alkyl groups, and C 7 -C 14 aralkyl groups, of which C 1 -C 6 alkyl groups, C 2 -C 6 alkenyl groups, C 2 -C 6 alkynyl groups and phenyl group are typically preferred. The rings formed by a combination of R 4 and R 5 , R 6 and R 7 , or R 4 and R 6 together with the adjacent carbon atom or carbon-carbon bond include cyclopropane, cyclobutane, cyclopentane, cyclopentene, cyclohexane, cyclohexene, cyclooctane, cyclododecane, and other non-aromatic carbocyclic rings (cycloalkane rings and cycloalkene rings) and non-aromatic heterocyclic rings each having 3 to 20 members. Each of these rings may have any of the aforementioned substituents, and may have another ring (a non-aromatic or aromatic ring) condensed thereto. Preferred substituents R 4 , R 5 , R 6 , and R 7 include a hydrogen atom and the groups exemplified as the preferred hydrocarbon groups. Typical examples of the epoxy compounds of the formula (2) include, but are not limited to, ethylene oxide, propylene oxide, 1,2-epoxybutane, 1,2-epoxypentane, 1,2-epoxyhexane, 1,2-epoxy-2-methylpropane, 1,2-epoxy-2-methylbutane, 2,3-epoxy-2-methylbutane, 2,3-epoxy-2,3-dimethylbutane, styrene oxide, and α-methylstyrene oxide. The epoxy compounds of the formula (2) can be obtained by, for example, reacting corresponding olefins (R 4 R 5 C=CR 6 R 7 ) with peracids. [Reaction] The reaction in the invented process is conducted in the presence of compounds of Group 3 or 4 elements of the Periodic Table of Elements, especially compounds of Group 3 elements of the Periodic Table of Elements. The valency of the metal element in the metallic compound is not particularly limited, and is from 0 to 4, and typically from 2 to 4 in many cases. Such metallic compounds include, but are not limited to, hydroxides, oxides (including complex oxides), halides (fluorides, chlorides, bromides, and iodides), salts of oxo acids (e.g., nitrates, sulfates, phosphates, borates, and carbonates), oxo acids, isopolyacids or their salts, heteropolyacids or their salts, and other inorganic compounds; salts of organic acids (e.g., salts of, hydrocyanic acid; acetic acid, trichloroacetic acid, trifluoroacetic acid, propionic acid, naphthenic acid, stearic acid, maleic acid, tartaric acid, and other carboxylic acids; methanesulfonic acid, trifluoromethanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, and other sulfonic acids), complexes, and other organic compounds. Such ligands to constitute the complexes include OH (hydroxo), alkoxy (e.g., methoxy, ethoxy, propoxy, and butoxy), acyl (e.g., acetyl, and propionyl), alkoxycarbonyl (e.g., methoxycarbonyl, and ethoxycarbonyl), acetylacetonato, cyclopentadienyl group, C 1 -C 4 alkylsubstituted dicyclopentadienyl groups (e.g., pentamethyldicyclopentadienyl), C 1 -C 4 alkyl groups (e.g., methyl and ethyl groups), halogen atoms (e.g., chlorine, and bromine atoms), CO, CN, oxygen atom, H 2 O (aquo), phosphines (triphenylphosphine, and other triarylphosphines), and other phosphorus compounds, NH 3 (amine), NO, NO 2 (nitro), NO 3 (nitrato), ethylenediamine, diethylenetriamine, pyridine, phenanthroline, and other nitrogen-containing compounds, tetrahydrofuran, and other oxygen-containing compounds. The compounds of Group 3 and Group 4 elements of the Periodic Table of Elements will now be described in further detail. The Group 3 elements of the Periodic Table of Elements include rare earth elements [e.g., scandium, yttrium, and lanthanoids elements (lanthanum, cerium, praseodymium, neodymium, promethium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, and lutetium)], and actinoids elements (e.g., actinium) Preferred Group 3 elements of the Periodic Table of Elements are rare earth elements, and are typically lanthanoids elements, of which samarium is specifically preferred. The Group 4 elements of the Periodic Table of Elements include titanium, zirconium, and hafnium. By taking samarium compounds as example, concrete examples of the compounds of Group 3 elements of Periodic Table of Elements include samarium(II) hydroxide, samarium(III) hydroxide, samarium(II) oxide, samarium(III) oxide, samarium(II) iodide, samarium(III) iodide, samarium(II) bromide, samarium(III) bromide, samarium(II) chloride, samarium(III) chloride, samarium(II) nitrate, samarium(II) sulfate, samarium(II) phosphate, samarium(II) carbonate, and other inorganic compounds; samarium(II) acetate, samarium(III) acetate, samarium(II) trichloroacetate, samarium(III) trichloroacetate, samarium(II) trifluoroacetate, samarium(III) trifluoroacetate, samarium (II) trifluoromethanesulfonate, samarium(III) trifluoromethanesulfonate, acetylacetonatosamarium(II), acetylacetonatosamarium(III), chlorobis (η-cyclopentadienyl) samarium(III), chlorobis(η-pentamethylcyclopentadienyl)samarium(III)-tetrahydrofur an, dichlorobis(η-penradienyl) samarium (III)-tetrahydrofuran, lithium tetra(allyl) samarium (III), tetra (t-buryl) lithiumsamarium (III)-tecrahydrofuran, tris(η-cyclopentadienyl)samarium(III), bis(η-pentamethylcyclopentadienyl) samarium (II)-tetrahydrofura n, hydridobis(η-pentamethylcyclopentadienyl)samarium(III) and alkylsamarium(II) iodide. As compounds of the other Group 3 elements of the Periodic Table of Elements, those corresponding to the samarium compounds can be mentioned. By taking zirconium compounds as example, practical examples of the compounds of Group 4 elements of the Periodic Table of Elements include zirconium(IV) hydroxide, zirconium(IV) oxide, zirconium(IV) iodide, zirconyl(IV) iodide, zirconium(IV) bromide, zirconyl(IV) bromide, zirconium(IV) chloride, zirconyl(IV) chloride, zirconium(IV) nitrate, zirconyl(IV) nitrate, zirconium(IV) sulfate, zirconyl(IV) sulfate, zirconium(IV) phosphate, zirconyl(IV) phosphate, zirconium(IV) carbonate, zirconyl(IV) carbonate, and other inorganic compounds; and zirconium(IV) oxalate, acetylacetonatozirconium(IV), chlorobis(η-cyclopentadienyl)methylzirconium(IV), trichloro(η-cyclopentadienyl)zirconium( IV), trichloro (η-pentamethylcyclopentadienyl)zirconium(IV), bis(η-pentamethylcyclopentadienyl)diiodozirconium(IV), and other organic compounds. As compounds of the other Group 4 elements of the Periodic Table of Elements, those corresponding to the zirconium compounds can be mentioned. The catalyst can be used either in a homogenous system or in a heterogenous system. The catalyst may be used as being supported by a carrier. As the carrier, activated carbon, silica, alumina, silica-alumina, zeolite, or other porous carriers are used in many cases. The ratio of the catalytic component to the carrier is, for example, 0.1 to 50 parts by weight, and preferably 0.5 to 30 parts by weight relative to 100 parts by weight of the carrier. Each of the above catalysts can be used alone or in combination. The amount of the catalyst can be selected within a wide range, and is, for example, from 0.00001 to 1 mole, preferably from 0.001 to 0.5 mole, and more preferably from 0.01 to 0.25 mole relative to 1 mole of the compound of the formula (1). The reaction between the imine derivative of the formula (1) and the epoxy compound of the formula (2) is performed in the presence of, or in the absence of, a solvent. Such solvents include, but are not limited to, hexane, octane, and other aliphatic hydrocarbons; cyclohexane and other alicyclic hydrocarbons; benzene, toluene, and other aromatic hydrocarbons; chloroform, dichloromethane, dichloroethane, carbon tetrachloride, chlorobenzene, trifluoromethylbenzene, and other halogenated hydrocarbons; acetone, ethyl methyl ketone, cyclohexanone, and other ketones; diethyl ether, diisopropyl ether, dimethoxyethane, tetrahydrofuran (THF), dioxane, and other ethers; ethyl acetate, butyl acetate, and other esters; acetoniirile, propiononitrile, benzonitrile, and other nitriles; dimethylformamide (DMF), dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, and other non-protic polar solvents; and mixtures of these solvents. Preferred solvents are ethers and non-protic polar solvents, for example. The proportion of the imine derivative of the formula (1) to the epoxy compound of the formula (2) can be selected within an appropriate range according production costs and reactivity, and either one of the two reactants can be used in an excessive amount relative to the other. For example, the epoxy compound can be used in an amount of 1.1 to 3 moles relative to 1 mole of the imine compound. The reaction temperature can be selected within an appropriate range according to, for example, the species of the reactants, and falls in the range from -20°C to +200°C, preferably from 0°C to 150°C, more preferably from 0°C to 100°C, and typically from 10°C to 60°C. The reaction time may be selected within an appropriate range of, for example, from 10 minutes to 48 hours. The reaction may be performed in a batch system, a semi-batch system or a continuous system. The reaction between the imine derivative of the formula (1) and the epoxy compound of the formula (2) yields a corresponding adduct, i.e. a 1,3-oxazolidine derivative of the formula (3). The nitrogen atom of the imine derivative may be generally bonded to one carbon atom that exhibits a less steric hindrance of the two carbon atoms constituting the epoxy group of the epoxy compound. After the completion of the reaction, reaction products can be easily separated and purified in a conventional manner. Such conventional manners include, for example, filtration, concentration, distillation, extraction, crystallization, recrystallization, column chromatography and other separation and purification means, or any combination of these means. According to the invention, 1,3-oxazolidine derivatives can be easily and efficiently obtained from readily available materials. In addition, a wide variety of 1, 3-oxazolidine derivatives can be obtained in good yields and the invented process is satisfactory for general purpose use. The present invention will now be illustrated in more detail with reference to the examples below. EXAMPLE 1 A mixture of 1 mmol of N-isopropylidenebenzylamine, 2 mmol of 1,2-epoxy-2-methylpropane, 0.05 mmol of samarium (II) iodide (SmI 2 ) , and 1 ml of tetrahydrofuran was stirred at room temperature for 5 hours. The isolation of products in a reaction mixture by column chromatography revealed that 3-benzyl-2,2, 5, 5-tetramethyl-1,3-oxazolidine was formed in yield of 98%. EXAMPLE 2 (Comparative Example) The procedure of Example 1 was repeated, except that samarium(II) iodide (SmI 2 ) was not used, to yield 3-benzyl-2,2,5,5-tetramethyl-1,3-oxazolidine in yield of 20%. EXAMPLE 3 A mixture of 1 mmol of N-isopropylidenebutylamine, 2 mmol of 1,2-epoxy-2-methylpropane, 0.05 mmol of samarium(II) iodide (SmI 2 ), and 1 ml of tetrahydrofuran was stirred at room temperature for 5 hours. The isolation of products in a reaction mixture by column chromatography revealed that 3-butyl-2,2,5,5-tetramethyl-1,3-oxazolidine was formed in yield of 92%. EXMPLE 4 A mixture of 1 mmol of N-(2-ethylpropylidene)butylamine, 2 mmol of 1,2-epoxy-2-methylpropane, 0.05 mmol of samarium(II) iodide (SmI 2 ), and 1 ml of tetrahydrofuran was stirred at room temperature for 5 hours. The isolation of products in a reaction mixture by column chromatography revealed that 3-butyl-2,2-diethyl-5,5-dimethyl-1,3-oxazolidine was formed in yield of 90%. EXAMPLE 5 A mixture of 1 mmol of N-cyclohexylidenebutylamine, 2 mmol of 1,2-epoxy-2-methylpropane, 0.05 mmol of samarium (II) iodide (SmI 2 ) , and 1 ml of tetrahydrofuran was stirred at room temperature for 5 hours. Produces in the reaction mixture was isolated through column chromatography to yield 4-aza-4-butyl-2,2-dimethyl-1-oxaspiro[4.5] decane of the following formula in yield of 85%. EXAMPLE 6 A mixture of 1 mmol of N- (1-methylbutylidene)butylamine, 2 mmol of 1,2-epoxy-2-methylpropane, 0.05 mmol of samarium (II) iodide (SmI 2 ), and 1 ml of tetrahydrofuran was stirred at room temperature for 5 hours. Column chromatographic isolation of products in a reaction mixture revealed that 3-butyl-2,5,5-trimethyl-2-propyl-1,3-oxazolidine was formed in yield of 59%. EXAMPLE 7 A mixture of 1 mmol of N-butylidenebutylamine, 2 mmol of 1,2-epoxy-2-methylpropane, 0.05 mmol of Cp - 2 Sm (THF) 2 , and 1 ml of tetrahydrofuran was stirred at room temperature for 5 hours. Products in a reaction mixture were isolated through column chromatography to yield 3-butyl-5,5-dimethyl-2-propyl-1,3-oxazolidine in yield of 53%.

Claims: A process for producing 1,3-oxazolidine derivatives, said process comprising: reacting an imine derivative of the following formula (1): wherein R 1 and R 2 are each, identical to or different from each other, a hydrogen atom; an aliphatic hydrocarbon group selected from C 1-10 alkyl groups, C 2-10 alkenyl groups and C 2-10 alkynyl groups, an alicyclic hydrocarbon group selected from 3 to 12-membered cycloalkyl groups and 3 to 12-membered cycloalkenyl groups, a C 6-10 aromatic hydrocarbon group, or a group formed from these groups combined together; or a heterocyclic group selected from 5-membered rings, 6-membered rings and condensed rings each containing a hetero atom selected from oxygen, sulfur and nitrogen; R 3 is a hydrogen atom; an aliphatic hydrocarbon group selected from C 1-10 alkyl groups, C 2-10 alkenyl groups and C 2-10 alkynyl groups, an alicyclic hydrocarbon group selected from 3 to 12-membered cycloalkyl groups and 3 to 12-membered cycloalkenyl groups, a C 6-10 aromatic hydrocarbon group, or a group formed from these groups combined together, a heterocyclic group selected from 5-membered rings, 6-membered rings and condensed rings each containing a hetero atom selected from oxygen, sulfur and nitrogen; a hydroxyl group; a substituted oxy group, said oxy group being selected from C 1-10 alkoxy groups, aryloxy groups and aralkyloxy groups; an amino group, a mono- or di-C 1-6 alkylamino group or a cyclic amino group; where R 1 and R 2 may be combined to form a ring with the adjacent carbon atom, said ring being selected from 3 to 20-membered non-aromatic carbocydic rings and non-aromatic heterocyclic rings; with an epoxy compound of the following formula (2): wherein R 4 , R 5 , R 6 and R 7 are each, identical to or different from one another, a hydrogen atom, an aliphatic hydrocarbon group selected from C 1-10 alkyl groups, C 2-10 alkenyl groups and C 2-10 alkynyl groups, an alicyclic hydrocarbon group selected from 3 to 12-membered cycloalkyl groups and 3 to 12-membered cycloalkenyl groups, a C 6-10 aromatic hydrocarbon group, or a group formed from these groups combined together; or heterocyclic group selected from 5-membered rings, 6-membered rings and condensed rings each containing a hetero atom selected from oxygen, sulfur and nitrogen; where each combination of R 4 and R 5 , R 6 and R 7 , or R 4 and R 6 may be combined to form a ring with the adjacent carbon atom or the adjacent carbon-carbon bond, said ring being selected from 3 to 20-membered non-aromatic carbocyclic rings and non-aromatic heterocyclic rings; to yield an oxazolidine derivative of the following formula (3): wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 have the same meanings as defined above; and wherein the reaction is performed in the presence of a metallic compound catalyst comprising a compound of Group 3 or 4 element of the Periodic Table of Elements. The process according to claim 1, wherein said metallic compound catalyst is a compound of a Group 3 element of the Periodic Table of Elements.

Inventors: ISHII YASUTAKA, NAKANO TATSUYA, ISHII, YASUTAKA, NAKANO, TATSUYA
Applicants: DAICEL CHEM, DAICEL CHEMICAL INDUSTRIES, LTD.
Application year: 2000
Main classification: C07D263
IPC codes: C07B61, C07D263, B01J27