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GB1560711A - Isoxazoles and manufacture thereof - Google Patents

Isoxazoles and manufacture thereof Download PDF

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Publication number
GB1560711A
GB1560711A GB45888/76A GB4588876A GB1560711A GB 1560711 A GB1560711 A GB 1560711A GB 45888/76 A GB45888/76 A GB 45888/76A GB 4588876 A GB4588876 A GB 4588876A GB 1560711 A GB1560711 A GB 1560711A
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general formula
compounds
carbon atoms
branched
alkyl
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BASF SE
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BASF SE
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D261/00Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/08Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/547Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6527Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07F9/653Five-membered rings

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Description

(54) NEW ISOXAZOLES AND MANUFACTURE THEREOF (71) We, BASF AKTIENGESELLSCHAFT, a German Joint Stock Com pany of 6700 Ludwigshafen, Federal Republic of Germany, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: The present invention provides new compounds of the general formula
wherein R1 denotes linear or branched, unsubstituted or halogen-, alkoxy- or alkylthiosubstituted C1 to C10 alkl, R2 denotes linear or branched C, to C, alkyl or, provided that R1 contains 4 or more carbon atoms and/or a halogen oxygen or sulfur atom, hydrogen, and X denotes halogen. Isoxazoles of the general formula I are valuable intermediates for the production of biologically active compounds.
The present invention further provides a process for the manufacture of the new isoxazoles of the general formula I by reaction of nitrile oxides of the general formula II with acetylene compounds of the general formula III, Rt, R2 and X having the meanings given above.
It is surprising that nitrile oxides of the general formula II do not react with acetylene compounds of the general formula III to give isoxazoles of the general formula IX, but that, in a regiospecific reaction, isoxazoles of the general formula I according to the invention are formed:
because it is known from Grundmann (Houben-Weyl, Methoden der organischen Chemie, 10/3, p. 860, Georg Thieme-Verlag, Stuttgart, 4th ed., 1965) that in reactions of nitrile oxides with acetylene compounds nitrile oxides of the general formula VI add on to acetylene compounds of the general formula VII in such a manner that the centres of the opposing partial charges face each other. The chemical bond between these centres then results in isoxazole derivatives of the general formula VIII:
Since the following partial charge distributions (C. K. Ingold, Structure and Mechanism in Organic Chemistry, Cornell University Press, Ithaca, New York, 1953, p. 149) are present as a result of the negative induction effect of halogen atoms in the acetylene compounds of the general formula III:
the nitrile oxides of the general formula II would have been expected to add on to the acetylene compounds of the general formula III in accordance with Grundmann' 5 scheme to give isoxazoles of the general formula IX:
The nitrile oxides of the general formula II required as starting compounds may be easily prepared by generally known processes (Houben-Weyl, Methoden der organischen Chemie, 10/3, p. 837, George Thieme-Verlag, Stuttgart, 4th ed., 1965; J. Org. Chem., 28, 1150, 1963), for instance by reaction of aliphatic nitro compounds of the general formula IV with water-eliminating agents or by dehydrohalogenation of hydroxamic halides, especially chlorides, of the general formula V.
Aliphatic nitro compounds may be prepared by the processes described in Houben Weyl, Methoden der organischen Chemie, 10/1, pp. 1461, George Thierne-Verlag, Stuttgart, 4th ed., 1971, and hydroxamic halides by the processes described in Houben Weyl, Methoden der organischen Chemie, 10/4, pp. 98-128, George Thieme-Verlag, Stuttgart, 4th ed.
The nitrile oxides of the general formula II and the acetylene compounds of the general formula III may be reacted in equimolar amounts; alternatively, either of the two reactants may be used in excess.
It is, however, not necessary to isolate the nitrile oxides of the general formula II before the reaction of the invention; indeed it is advantageous to produce the nitrile oxides of the general formula II in the presence of the acetylene compounds of the general formula III. The reactive nitrile oxides then react in situ with the acetylene compounds to give isoxazoles of the general formula I according to the invention.
A suitable solvent in which the reaction proceeds is an excess of the acetylene compound of the general formula m. Examples of other suitable solvents are aromatic compounds, such as benzene, toluene, xylene and halogenated aromatic compounds; ketones, such as acetone, methyl ethyl ketone and diisopropyl ketone; ethers, such as dioxane, diethyl ether and tetrahydrofuran; and chlorinated hydrocarbons, such as dichloroethane, chloroform and methylene chloride.
It is advantageous to carry out the reaction at atmospheric pressure and temperatures of from 200 to + 1500 C; temperatures of from 0 to 100"C are preferred.
To bind hydrogen halide formed in the reaction it is expedient to add a base, e.g., a tertiary amine.
Individual examples of radicals R' are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl and the branched isomers of these alkyl radicals. The same applies to radicals R2 with 1 to 6 carbon atoms. Examples of ether and thioether groups R1 are methoxypropyl, ethoxypropyl, methoxymethyl, ethoxymethyl, methoxyethyl, ethoxyethyl and the corresponding thioethers.
Fluorine, chlorine, bromine and iodine are suitable as halogen in radicals R1 and as X. An example of a halogen-substituted radical R1 is trifluoromethyl.
The structure of the starting compounds corresponds to the substituents in the compounds of the invention.
Individual compounds according to the invention are as follows: R1 R2 X ClI3 CH3 Br i-C3H, CH, Cl i-C3H7 C2H5 Cl CH,OCH,- H C1 i-C,H,--SS-CH, CH3 Br CiCH2- H Br F,C H Br
The following examples illustrate the process for the manufacture of these compounds of the invention. The structure of the isoxazoles obtained may be established with the aid of 'H-NMR spectroscopy and 13C-NMR spectroscopy.
Parts by weight bear the same relation to parts by volume as kilograms to liters.
EXAMPLE 1
149 parts by weight of propargyl chloride, 476 parts by weight of phenyl iso cyanate and 210 parts by weight of 2-methoxynitroethane are dissolved in 1,500 parts by volume of toluene; at 15 to 20"C, 1 part by volume of triethylamine is then added to activate the phenyl isocyanate. The temperature is kept for 3 hours at 150 to 300C, 1 part by volume of uiethylamine being added per hour. Subsequently, the mixture is stirred for 1 hour at 70"C, and then cooled. The precipitate is suction filtered and the residue washed with 1,000 parts by volume of toluene. The combined filtrates are concentrated and the residue is distilled under an oil pump vacuum. 5-chloromethyl3-methoxymethyl-isoxazole distils over.
EXAMPLE 2
93.5 parts by weight of acetohydroximoyl chloride (Ber. dtsch. chem. Ges., 40, 1677, 1907) and 90 parts by weight of isobutynyl chloride are stirred into 1,500 ml of benzene; at 15" to 20"C, 105 parts by weight of triethylamine is then added drop wise. The mixture is then stirred for 1 hour at 20 to 25"C and for 1 hour at 70 C.
After cooling, the mixture is filtered and the filtrate concentrated. The distillate which remains is distilled under an oil pump vacuum. There is obtained 133 parts by weight (92% of theory) of 3-(1-chloroethyl)-5-methyl isoxazole having a boiling point of 48" to 50"C/0.05 mm Hg; nod25: 1.4740.
C,HaNOCL (145.5) Calc.: C, 49.6; H, 5.5; N, 9.7; Cl, 24.5 Found: C, 49.5; H, 5.7; N, 10.0; Cl, 24.0 60 MHz nmr spectrum (CDCl; 3 values): 1.78 (d, 3H); 2.3 (s, 3H); 5.05 (9, lH); 6.09 (s, 1H).
3C mur spectrum (CDCl3; ppm values relative to TMS): 171.5 (C); 159.8 (C); 102.5 (CH); 47.4 (CH); 23.3 (CHs); 11.5 (CHs).
EXAMPLE 3
133 parts by weight of emethyl-propargyl bromide, 95 parts by weight of nitropropane and 440 parts by weight of triethylamine are dissolved in 1,200 parts by volume of chloroform; at 0 C, 155 parts by weight of phosphoroxy chloride is then added dropwise. The mixture is then heated for 30 minutes at 20"C and then reflexed for 2 hours. After cooling, the mixture is filtered and concentrated, and the residue is taken up in water. The water phase is extracted again with toluene, and the combined toluene phases are washed with water and then dried over sodium sulfate. The sodium sulfate is then separated and the filtrate concentrated; the residue is distilled under an oil pump vacuum.
5-(1-bromoethyl)-3ethyl isoxazole distils over: The following compounds are obtained analogously:
The significance of the new compounds lies firstly in their basic isoxazole structure and secondly in the substituent
in which the halogen X can readily be exchanged for other radicals which themselves can have a biological action or, for instance by changing lyophilic properties, only have auxiliary functions. The new compounds are thus suitable for the manufacture of various insecticides, herbicides, fungicides and nematocides; of particular importance are derivatives of phosphoric and phosphonic acid and their corresponding thiol, thione and thionothiol derivatives.
The phosphoric acid derivatives are obtained by reacting salts of phosphoric acid derivatives of the general formula XIII with isoxazole derivatives of the general formula I to give the phosphoric acid derivatives of the general formula XIV:
The radicals R1, R3 and X have the above meanings, Z denotes an alkali metal ion, an equivalent amount of an alkaline earth metal ion, or an ammonium ion optionally substituted by alkyl radicals, Y denotes oxygen or sulfur, R3 denotes linear or branched alkoxy of a maximum of 6 carbon atoms, linear or branched alkylthio, alkenylthio or alkylnylthio of a maximum of 6 carbon atoms, alkyl of a maximum of 3 carbon atoms, phenyl, or linear or branched alkylamino or dialkylamino of a maximum of 5 carbon atoms, and R4 denotes linear or branched alkyl of a maximum of 6 carbon atoms.
Phosphoric acid derivatives of the general formula XIV are described and claimed in our copending UK patent application No. 45889/76 (Serial No. 1,560,712). Further information on such compounds, their production and their pesticidal use is to be found in that application, to which attention is directed.
WHAT WE CLAIM IS:- 1. Compounds of the general formula
where R1 denotes linear or branched, unsubstituted or halogen-, alkoxy- or alkylthiosubstituted C1 to C,0 alkyl, R2 denotes linear or branched C1 to C, alkyl or, provided that R' contains 4 or more carbon atoms and/or a halogen, oxygen or sulfur atom, hydrogen, and X denotes halogen.
2. A process for producing a compound as claimed in claim 1, wherein a nitrile oxide of the general formula R1-C=-NO II ee where R1 has the meaning given in claim 1, is reacted with an acetylene compound of the general formula
where R2 and X have the meanings given in claim 1, in the presence or absence of a solvent.
3. A process as claimed in claim 2 carried out at from -20 to +150 C 4. A process as claimed in claim 2 or 3, wherein the nitrile oxide is formed in situ from the corresponding aliphatic nitro compound by elimination of water, or from the corresponding hydroxamic acid halide by dehydrohalogenation.
5. A process as claimed in any of claims 2 to 4, wherein the reaction of the nitrile oxide is carried out in the presence of a tertiary amine to bind hydrogen halide formed.
6. A process as claimed in any of claims 2 to 5, wherein the reaction of the nitrile oxide is carried out in the presence of excess acetylene compound III serving as solvent.
7. A process for producing a compound claimed in claim 1 carried out substantially as described in any of the foregoing Examples.
8. Compounds claimed in claim 1 when produced by a process as claimed in any of claims 2 to 7.
9. Compounds claimed in claim 1 or 8 and individually identified hereinbefore.
**WARNING** end of DESC field may overlap start of CLMS **.

Claims (9)

**WARNING** start of CLMS field may overlap end of DESC **. alkenylthio or alkylnylthio of a maximum of 6 carbon atoms, alkyl of a maximum of 3 carbon atoms, phenyl, or linear or branched alkylamino or dialkylamino of a maximum of 5 carbon atoms, and R4 denotes linear or branched alkyl of a maximum of 6 carbon atoms. Phosphoric acid derivatives of the general formula XIV are described and claimed in our copending UK patent application No. 45889/76 (Serial No. 1,560,712). Further information on such compounds, their production and their pesticidal use is to be found in that application, to which attention is directed. WHAT WE CLAIM IS:-
1. Compounds of the general formula
where R1 denotes linear or branched, unsubstituted or halogen-, alkoxy- or alkylthiosubstituted C1 to C,0 alkyl, R2 denotes linear or branched C1 to C, alkyl or, provided that R' contains 4 or more carbon atoms and/or a halogen, oxygen or sulfur atom, hydrogen, and X denotes halogen.
2. A process for producing a compound as claimed in claim 1, wherein a nitrile oxide of the general formula R1-C=-NO II ee where R1 has the meaning given in claim 1, is reacted with an acetylene compound of the general formula
where R2 and X have the meanings given in claim 1, in the presence or absence of a solvent.
3. A process as claimed in claim 2 carried out at from -20 to +150 C
4. A process as claimed in claim 2 or 3, wherein the nitrile oxide is formed in situ from the corresponding aliphatic nitro compound by elimination of water, or from the corresponding hydroxamic acid halide by dehydrohalogenation.
5. A process as claimed in any of claims 2 to 4, wherein the reaction of the nitrile oxide is carried out in the presence of a tertiary amine to bind hydrogen halide formed.
6. A process as claimed in any of claims 2 to 5, wherein the reaction of the nitrile oxide is carried out in the presence of excess acetylene compound III serving as solvent.
7. A process for producing a compound claimed in claim 1 carried out substantially as described in any of the foregoing Examples.
8. Compounds claimed in claim 1 when produced by a process as claimed in any of claims 2 to 7.
9. Compounds claimed in claim 1 or 8 and individually identified hereinbefore.
GB45888/76A 1975-11-07 1976-11-04 Isoxazoles and manufacture thereof Expired GB1560711A (en)

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Application Number Priority Date Filing Date Title
DE19752549962 DE2549962A1 (en) 1975-11-07 1975-11-07 NEW ISOXAZOLES AND THE METHOD OF MANUFACTURING THEM

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JP (1) JPS5259156A (en)
BE (1) BE847919A (en)
CH (1) CH599946A5 (en)
DE (1) DE2549962A1 (en)
FR (1) FR2330685A1 (en)
GB (1) GB1560711A (en)
IL (1) IL50691A (en)
IT (1) IT1121684B (en)
NL (1) NL7612247A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5006515A (en) * 1987-10-26 1991-04-09 Hoechst Aktiengesellschaft Pharmaceuticals, phosphorus-containing 2-isoxazolines and isoxazoles contained therein

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2818998A1 (en) * 1978-04-29 1979-11-15 Basf Ag 3-ALKYL-5- (2-HYDROXY-STYRYL) -ISOXAZOLES AND METHOD FOR THE PRODUCTION THEREOF
DE2943405A1 (en) * 1979-10-26 1981-05-07 Basf Ag, 6700 Ludwigshafen NEW AMINO DERIVATIVES OF 5- (2-HYDROXYSTYRYL) -ISOXAZOLE
DE3110767A1 (en) * 1981-03-19 1982-09-30 Basf Ag, 6700 Ludwigshafen FIGHTING MUSHROOMS WITH 1,2-OXAZOLYLALKYLPHOSPHATES
DE3742266A1 (en) * 1987-12-12 1989-06-22 Basf Ag 2-TERT.-BUTYL-5-ISOXAZOLYLMETHYLTHIO-3 (2H) -PYRIDAZINE-3-ON DERIVATIVES

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5006515A (en) * 1987-10-26 1991-04-09 Hoechst Aktiengesellschaft Pharmaceuticals, phosphorus-containing 2-isoxazolines and isoxazoles contained therein

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IT1121684B (en) 1986-04-10
FR2330685B1 (en) 1980-04-30
NL7612247A (en) 1977-05-10
CH599946A5 (en) 1978-06-15
JPS5259156A (en) 1977-05-16
IL50691A (en) 1979-07-25
FR2330685A1 (en) 1977-06-03
DE2549962A1 (en) 1977-05-18
BE847919A (en) 1977-05-03
IL50691A0 (en) 1976-12-31

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PS Patent sealed [section 19, patents act 1949]
PCNP Patent ceased through non-payment of renewal fee