MXPA97006651A - Preparation of substitute pirazols in the laposicio - Google Patents
Preparation of substitute pirazols in the laposicioInfo
- Publication number
- MXPA97006651A MXPA97006651A MXPA/A/1997/006651A MX9706651A MXPA97006651A MX PA97006651 A MXPA97006651 A MX PA97006651A MX 9706651 A MX9706651 A MX 9706651A MX PA97006651 A MXPA97006651 A MX PA97006651A
- Authority
- MX
- Mexico
- Prior art keywords
- preparation
- pyrazole
- formula
- molar ratio
- pyrazoles
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- -1 N-substituted pyrazoles Chemical class 0.000 claims abstract description 46
- 238000000034 method Methods 0.000 claims abstract description 25
- WTKZEGDFNFYCGP-UHFFFAOYSA-N pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000003054 catalyst Substances 0.000 claims abstract description 17
- 150000003217 pyrazoles Chemical class 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 10
- 125000003884 phenylalkyl group Chemical group 0.000 claims abstract description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000007791 liquid phase Substances 0.000 claims abstract description 6
- 150000008064 anhydrides Chemical class 0.000 claims abstract description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
- 239000001257 hydrogen Substances 0.000 claims abstract description 5
- 125000004435 hydrogen atoms Chemical class [H]* 0.000 claims abstract description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 23
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 150000001875 compounds Chemical class 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 6
- 150000007513 acids Chemical class 0.000 claims description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
- 125000005907 alkyl ester group Chemical group 0.000 claims description 5
- DLYUQMMRRRQYAE-UHFFFAOYSA-N Phosphorus pentoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 claims description 4
- AKEJUJNQAAGONA-UHFFFAOYSA-N Sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 claims description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 3
- 150000008050 dialkyl sulfates Chemical class 0.000 claims description 3
- 150000008051 alkyl sulfates Chemical class 0.000 claims 1
- 235000021317 phosphate Nutrition 0.000 claims 1
- 150000002148 esters Chemical class 0.000 abstract description 2
- 238000006555 catalytic reaction Methods 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 32
- JXHKUYQCEJILEI-UHFFFAOYSA-N 3,5-diphenyl-1H-pyrazole Chemical class C=1C(C=2C=CC=CC=2)=NNC=1C1=CC=CC=C1 JXHKUYQCEJILEI-UHFFFAOYSA-N 0.000 description 16
- 238000009835 boiling Methods 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- RIKMMFOAQPJVMX-UHFFFAOYSA-N fomepizole Chemical class CC=1C=NNC=1 RIKMMFOAQPJVMX-UHFFFAOYSA-N 0.000 description 8
- 229960004285 fomepizole Drugs 0.000 description 8
- 239000000155 melt Substances 0.000 description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N t-BuOH Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
- SZQCPPRPWDXLMM-UHFFFAOYSA-N 1,4-dimethylpyrazole Chemical compound CC=1C=NN(C)C=1 SZQCPPRPWDXLMM-UHFFFAOYSA-N 0.000 description 5
- 150000001298 alcohols Chemical class 0.000 description 4
- KBPLFHHGFOOTCA-UHFFFAOYSA-N octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 4
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N Dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 2
- QUSOBKIKODRYSH-UHFFFAOYSA-N 1-tert-butylpyrazole Chemical compound CC(C)(C)N1C=CC=N1 QUSOBKIKODRYSH-UHFFFAOYSA-N 0.000 description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
- 238000007126 N-alkylation reaction Methods 0.000 description 2
- 125000005037 alkyl phenyl group Chemical group 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N n-butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- SVDTUJAQNAQGGW-UHFFFAOYSA-N 1-methyl-3,5-diphenylpyrazole Chemical compound CN1N=C(C=2C=CC=CC=2)C=C1C1=CC=CC=C1 SVDTUJAQNAQGGW-UHFFFAOYSA-N 0.000 description 1
- YIWUKEYIRIRTPP-UHFFFAOYSA-N 2-Ethylhexanol Chemical compound CCCCC(CC)CO YIWUKEYIRIRTPP-UHFFFAOYSA-N 0.000 description 1
- 125000003229 2-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000003890 2-phenylbutyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- HUVAAOZUPLEYBH-UHFFFAOYSA-N 3,4,5-trimethyl-1H-pyrazole Chemical class CC1=NNC(C)=C1C HUVAAOZUPLEYBH-UHFFFAOYSA-N 0.000 description 1
- NAFYHLQTAPLJKI-UHFFFAOYSA-N 3,4,5-triphenyl-1H-pyrazole Chemical compound C1=CC=CC=C1C1=NNC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 NAFYHLQTAPLJKI-UHFFFAOYSA-N 0.000 description 1
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- VQTVFIMEENGCJA-UHFFFAOYSA-N 4,5-dimethyl-1H-pyrazole Chemical class CC=1C=NNC=1C VQTVFIMEENGCJA-UHFFFAOYSA-N 0.000 description 1
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 description 1
- JWCLALQIPRYQOE-UHFFFAOYSA-N 4-ethylpyrazole Chemical class CCC1=CN=N[CH]1 JWCLALQIPRYQOE-UHFFFAOYSA-N 0.000 description 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- CBNLNXLAIMQSTR-UHFFFAOYSA-N 5-ethyl-1H-pyrazole Chemical class CCC1=CC=NN1 CBNLNXLAIMQSTR-UHFFFAOYSA-N 0.000 description 1
- XKVUYEYANWFIJX-UHFFFAOYSA-N 5-methyl-1H-pyrazole Chemical class CC1=CC=NN1 XKVUYEYANWFIJX-UHFFFAOYSA-N 0.000 description 1
- OEDUIFSDODUDRK-UHFFFAOYSA-N 5-phenyl-1H-pyrazole Chemical compound N1N=CC=C1C1=CC=CC=C1 OEDUIFSDODUDRK-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N Benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- AQSJGOWTSHOLKH-UHFFFAOYSA-N Phosphite Chemical class [O-]P([O-])[O-] AQSJGOWTSHOLKH-UHFFFAOYSA-N 0.000 description 1
- 239000005092 Ruthenium Substances 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000002152 alkylating Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 230000003197 catalytic Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000002638 heterogeneous catalyst Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N iso-propanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- VQTUBCCKSQIDNK-UHFFFAOYSA-N isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000004433 nitrogen atoms Chemical group N* 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propanol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000011814 protection agent Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000002588 toxic Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
Abstract
The present invention relates to a process for the preparation of N-substituted pyrazoles of the general formula I, wherein R 1 is C 1 -C 12 alkyl or C 7 -C 20 phenylalkyl and R 2, R 3 and R 4 are, independently of each other, hydrogen, C 1 -C 12 alkyl-, C 7 -C 20 phenylalkyl or unsubstituted or substituted aryl radicals, comprising the catalytic reaction of the pyrazoles of the general formula II, wherein R 2, R 3 and R 4 have the meanings mentioned above, with an alcohol of the general formula III R1-OH, wherein R1 has the above-mentioned meaning, at 50 ° C to 400 ° C in the molar ratio from 0.001: 1 to 1: 1, in liquid phase, under a subatmospheric pressure of 0.8 bar up to a superatmospheric pressure of 250 bar, selecting as catalyst only alkyl acids or their esters or their anhydrides, in the molar ratio from 0.0001: 1 to 0.5: 1 with respect to pyrazole
Description
PREPARATION OF SUBSTITUTE PIRAZOLS IN POSITION N
The present invention relates to a process for the preparation of the N-substituted pyrazoles by reacting the pyrazoles with alcohols in the liquid phase, in the presence of catalysts, at elevated temperatures. DE-A-35 06 972 and US-A-3, 910, 949 describe a process for the N-alkylation of 3,5-diphenylpyrazoles, in which the 3,5-diphenylpyrazoles unsubstituted in the N-position are reacted with dimethyl sulfate / aqueous sodium hydroxide solution in the presence of a phase transfer catalyst. DE-A-24 25 979 describes the alkylation of the 3, 5-diarylpyrazoles with alkyl halides or dialkyl sulfates. The disadvantages of these processes are the use of relatively toxic and relatively expensive dialkyl sulfates, because most of this molecule is not used, and a large amount of salt is produced. Chemical Letters (1992) 575-578 describes a process for the N-alkylation of pyrazoles in which the N-unsubstituted pyrazoles are reacted with alcohols in the presence of catalytic amounts of ruthenium, rhodium or iridium / trialkyl phosphite complexes.
The disadvantage of this process is the high cost of the catalysts. The patents of DE-A-43 18 960 and DE-A-44 03 815 describe a process for the alkylation at the N atom of the N-unsubstituted pyrazoles, in which the N-unsubstituted pyrazoles are reacted with alcohols or ethers in the presence of heterogeneous catalysts in gas phase. The disadvantage of this process is, especially in the case of pyrazoles unsubstituted at very high boiling point N, the need to vaporize the initial materials. An object of the present invention is to develop a more direct or less costly process for the preparation of the N-substituted pyrazoles. We have found that this objective is achieved by a novel and improved process for the preparation of the N-substituted pyrazoles of the formula General I.
wherein R 1 is C 1 -C 12 alkyl or C 7 -C 2 phenylalkyl and R 2 and R 4 are, independently from each other, hydrogen, C 1 -C 12 alkyl / C 7 -C 20 phenylalkyl or unsubstituted or substituted aryl radicals, by reaction of the pyrazoles of the general formula II.
wherein R2, R3 and R4 have the meanings mentioned above, with an alcohol of the general formula III R ^ OH (III), wherein R1 has the above-mentioned meaning, at 50 -400 ° C in the presence of a catalyst, in where the reaction of pyrazole II with compound III in the molar ratio from 0.001: 1 to 1: 1 is carried out in liquid phase under a pressure that is slightly below atmospheric or up to a pressure of 250 bar and acids are used and / or their alkyl esters or their anhydrides, in a molar ratio from 0.0001: 1 to 0.5: 1 with respect to pyrazole II, as a catalyst. The N-substituted pyrazoles I have a lower boiling point than the non-N-substituted pyrazoles II and are continuously discharged from the reactor in gaseous form with excess alkylating reagent III, but the discharge of the product during the reaction is not mandatory. The process according to the invention can be carried out in the following manner: The reaction can be carried out by contacting a pyrazole II with an alcohol III in the presence of one of the described catalysts at 50 to 400 ° C, preferably from 100 to 350 ° C under a pressure that is slightly lower or above atmospheric, that is, at a pressure from 0.8 to 250 bar, preferably from 0.8 to 100 bar, particularly preferably from 0.9 to 100 bar. The molar ratio of pyrazole II to compound III is, as a general rule, from 0.001: 1 to 1: 1, preferably 0.002: 1 to 1: 1, particularly preferably 0.003: 1 to 1: 1. Particularly preferably the reaction is carried out at temperatures, under a pressure and with molar ratios at which the pyrazole II and the catalyst are in the liquid phase, and the pyrazole I substituted in N and the unreacted compound III are discharged together, in gaseous form, from the reaction vessel. In pyrazole II and the catalyst can initially be dissolved or suspended in an inert solvent such as white oil or vacuum gas oil. Suitable catalysts are compounds such as sulfuric acid, phosphoric acid, alkyl or aryl sulfonic acids and their esters or their alkyl anhydrides. The molar ratio of the catalyst to pyrazole II is, as a general rule, from 0.0001: 1 to 0.5: 1, preferably from 0.0005: 1 to 0.5: 1, particularly preferably from 0.01: 1 to 0.2: 1. In comparison with the processes that have been described, the process according to the invention provides N-substituted pyrazoles in a more direct and economic way. Suitable as initial compounds II are pyrazoles, such as pyrazole and substituted pyrazoles, 3-methylpyrazole, 4-methylpyrazole, 3,4-dimethylpyrazole, 3,4,5-trimethylpyrazole, 3-ethylpyrazole, 4-ethylpyrazole, 3 -arilpyrazoles, 3-phenylpyrazole, 3,5-diarylpyrazoles, 3,5-diphenylpyrazole, 3-diarylpyrazoles, 3-diphenylpyrazole, 3, 4, 5-triarylpyrazoles and 3,4,5-triphenylpyrazole. Suitable as initial compounds III are alcohols, such as methanol, ethanol, n-propanol, isopropanol, n-butanol, tert-butanol and n-octanol, and the like. The I N-substituted pyrazoles which can be prepared by the process according to the invention are valuable starting materials for the preparation of dyes, medicaments and crop protection agents. The substituents R1 R2 R3 R4 and R5 in compounds I, II and III have the following meanings:
R1 R2 R3 R4 and R5 independent from each other C? -C? 2 alkyl / preferably C? -C8 alkyl such as methyl, aryl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, ter -butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, n-hexyl, isohexyl, sec-hexyl, n-heptyl, isoheptyl, n-heptyl, isooctyl, particularly preferably C 1 -C alkyl such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl. C 7 -C 2 phenylalkyl, preferably C 7 -C 12 phenylalkyl such as benzyl, 1-phenylethyl, 2-phenylethyl, 1-phenylpropyl, 2-phenylpropyl, 3-phenylpropyl, 1-phenylbutyl, 2-phenylbutyl, 3-phenylbutyl and 4-phenyl phenylbutyl, particularly preferably benzyl, 1-phenylethyl and 2-phenylethyl, R 2, R 3, R 4 independently of one another aryl hydrogen, preferably phenyl, - substituted aryl radicals such as C 7 -C 2 alkylphenyl, preferably C 7 -C 12 alkylphenyl, 2- methylphenyl, 3-methylphenyl, 4-methylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3, -dimethylphenyl, 3,5-dimethylphenyl, 2,3,4-trimethylphenyl, 2 , 3, 5-trimethylphenyl, 2,3,6-trimethylphenyl, 2,4,6-trimethylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 2-n-propylphenyl, 3-n-propylphenyl and 4-n -propylphenyl.
Examples Example 1 50g (0.2273 mol) of 3, 5-diphenylpyrazole and 5g (0.0437 mol) of phosphoric acid at 85% concentration were introduced into a bubble column at 250 ° C, a total of 158.2 g (4-94 mol) ) methanol was passed through, during the course of 4 hours and the gas discharge condensed. Subsequently 2 portions each of 50 g (0.2273 mol) of 3,5-diphenylpyrazole were introduced and reacted with 158.2 g (4.94 mol) of methanol in each case and condensed as in the above. Subsequently 31.5 g (0.143 mol) of 3,5-diphenylpyrazole were introduced, and 158.2 g (4.94 mol) of methanol were again passed through and condensed. Then, 158.2 g (4.94 mol) of methanol was passed through without introducing 3,5-diphenylpyrazole. All these five batches were collected separately, analyzed by gas chromatography and concentrated under reduced pressure. Lot No: Molar ratio: l-methyl-3,5- Discharge diphenylpyrazole / 3, 5 diphenylpyrazole [g] 1 94: 6 29.4 2 96.9: 3.1 46.4 3 97.8: 2.2 47.1 4 94.7: 5.3 35.3 5 100: O 23.7
A total of 181.5 g (0.825 mol) of 3,5-diphenylpyrazole and 791 g (24.7 mol) of methanol was used. A total of 175.8 g (91%) of l-methyl-3,5-diphenylpyrazole was obtained. The retention in the bubble column was not taken into account.
EXAMPLE 2 308.5 g (9.64 mol) of methanol were vaporized dropwise at 155 ° C in an electrically heated column, with a diameter of 4 cm and equipped with a sintered disk at the lower end and fitted on a double neck flask, of 250 ml, during the course of 6 hours and passed through a melt at 200 ° C, 10 g (0.0455 mol) of 3,5-diphenylpyrazole and 0.046 g (0.000455 mol) of concentrated H2SO4. The gaseous discharge of the reaction was condensed and concentrated under reduced pressure. There were obtained 10.2 g (92.5%) of l-methyl-3,5-diphenylpyrazole, boiling point 190 ° C / 3 mbar, with a content of 96.6% (GC).
Example 3 As in Example 2, a melt of 10 g (0.0455 mol) of 3,5-diphenylpyrazole and 0.051 g / (0.000455 mol) of methyl sulfate were introduced and reacted for 3 hours with 197.75 g (6.18 mol) of gaseous methanol (vaporized at 160 ° C). 9.7 g (86.7%) of l-methyl-3,5-diphenylpyrazole, boiling point 190 ° C / 3 mbar, with a content of 95.2% (GC), were obtained.
EXAMPLE 4 As in Example 2, at 200 ° C a melt was prepared consisting of 10 g (0.0455 mol) of 3,5-diphenylpyrazole and 0.057 g (0.00455 mol) of dimethyl sulfate. During the course of 5 hours, 435 g (13.6 mol) of methanol was vaporized at 155 ° C and passed through the melt, which was maintained at 200 ° C. 10.4 g (96.9%) of l-methyl-3, 5-diphenylpyrazole with a boiling point of 190 ° C / 3 mbar, with a content of 99.2% (GC), were obtained.
Example 5 10 g (0.122 mol) of 4-methylpyrazole, 1.25 g (0.0122 mol) of sulfuric acid and 20 g of Raschig glass rings with a diameter of 3 mm were heated to 145 ° C as in Example 2 and made The reaction at 145 ° C over the course of 5 hours with 118.65 g (3.7 mol) of vaporized methanol at 170 ° C, after concentration at atmospheric pressure gave 11.2 g (94.4%) of 1,4-dimethylpyrazole, with boiling point 151 ° C, with a content of 98.6% (GC).
Example 6 As in Example 5, 10 g (0.122 mol) of 4-methylpyrazole was heated with 1.37 g (0.0122 mol) of methyl sulfate at 190 ° C and reacted over the course of 3 hours with 79.1 g (2.47 g). mol) of vaporized methanol at 158 ° C. Obtained 11.5 g (93.5%) of 1,4-dimethylpyrazole, boiling point 151 ° C, with a content of 95.2% (GC).
Example 7 As in Example 5, 10 g (0.122 mol) of 4-methylpyrazole were heated with 1.54 g (0.0122 mol) of dimethyl sulfate at 195 ° C and reacted over the course of 3 hours with 118.72 g (3.71 g). mol) of vaporized methanol at 155 ° C. There were obtained 11.6 g (95.4%) of 1,4-dimethylpyrazole, boiling point 151 ° C, with a content of 96.3% (GC).
Example 8 As in Example 5, 10 g (0.122 mol) of 4-methylpyrazole was heated with 2 g (0.025 mol) of sulfur trioxide at 160 ° C and reacted over the course of 4 hours with 180 g (5.63 g). mol) of vaporized methanol at 130 ° C. There were obtained 10.6 g (84.9%) of 1,4-dimethylpyrazole, boiling point 151 ° C, with a content of 93.8% (GC).
Example 9 As in Example 5, 10 g (0.122 mol) of 4-methylpyrazole was heated with 2 g (0.014 mol) of phosphorus pentoxide at 150 ° C and reacted over the course of 3.5 hours with 175 g (5.5 mol) of methanol vaporized at 125 ° C. 10.9 g (89.5%) of 1,4-dimethylpyrazole, boiling point 151 ° C, with a content of 96.2% (GC) were obtained.
Example 10 As in Example 2, a melt of 10 g (0.04455 mol) of 3,5-diphenylpyrazole and 0.72 g (0.00455 mol) of benzenesulfonic acid were introduced and reacted over the course of 4.5 hours with 245 g ( 7.66 mol) of gaseous methanol (vaporized at 80 ° C). 9.6 g were obtained
(88.5%) of l-methyl-3, 5-diphenylpyrazole, boiling point 190 ° C / 3 mbar, with a content of 98.2% (GC).
EXAMPLE 11 As in Example 2, a melt of 10 g (0.0455 mol) of 3,5-diphenylpyrazole and 0.44 g (0.0045 mol) of methanesulfonic acid were introduced and reacted over the course of 4 hours with 175 g ( 5.46 mol) of gaseous methanol (vaporized at 160 ° C). 10 g (92%) of 1-methyl-3,5-diphenylpyrazole, boiling point 190 ° C / 3 mbar, were obtained.
with a content of 98% (CG).
Example 12 As in Example 2, the column was charged with 30 g of 3 mm diameter glass rings, 16.4 g (0.24 mol) of pyrazole and 1.02 g (0.01 mol) of 96% sulfuric acid by weight, heated to 195 ° C and reacted over the course of 7 hours with 703 g (9.5 mol) of vaporized tert-butanol at 180 ° C. There were obtained 21.7 g of n-tert-butylpyrazole, boiling point 103 ° C, with a content of 99.4% (GC), which corresponds to a yield of 72.5%.
Example 13 20.5 g (0.25 mol) of 4-methylpyrazole, 82 g (0.65 mol) of n-octanol and 1.28 g (0.0125 mol) of 96% sulfuric acid by weight were stirred at 175 ° C for 33 hours. After cooling, the mixture was extracted three times with 15 ml of sulfuric acid at 5% concentration each time. The combined sulfuric acid extracts were neutralized with a 25% sodium hydroxide solution. The subsequent distillation produced 13.5 g of the product, which was, according to the CG analysis, 99.3% of 4-methylpyrazole which did not react. 17.4 g of 4-methyl-n-octylpyrazole were obtained from the organic phase, boiling point 75 ° C / 7 mbar with a content of 95% (GC) and with a conversion of 34.6% and a selectivity of 98.5%.
Example 14 6.8 g (0.1 mol) of pyrazole, 23.7 g (0.32 mol) of tert-butanol and 0.51 g (0.005 mol) of sulfuric acid 96% by weight were stirred in an autoclave at 200 ° C and 35 bar for 3 hours. hours. After cooling, decompression (expulsion of isobutylene) and separation of the phase, 6.5 g of an aqueous pyrazole solution was obtained, which was 10.2% by weight according to the CG analysis and the distillation of this produced 6.66 g of pyrazole. 10.5 g (83.6%) of n-tert-butylpyrazole were obtained from the organic phase, boiling point 102 ° C, with a content of 98.8% (GC).
Example 15 34 g (0.5 mol) of pyrazole and 83 g (0.64 mol) of 2-ethyl-1-hexanol were stirred with 2.55 g (0.025 mol) of 96% sulfuric acid by weight at 175 ° C for 20 hours. After cooling, the mixture was extracted 3 times with 15 ml of 5% sulfuric acid each time. The combined sulfuric acid extracts were neutralized with 25% sodium hydroxide solution. The subsequent distillation yielded 27.0 g of, according to the GC analysis, 99.1% pure pyrazole which did not react. 19.6 g of n-hexyl-2-ethylpyrazole were obtained from the organic phase, boiling point 65 ° C / 50 steal, with a content of 92% (GC) and with a conversion of 21.3% and a selectivity of 93.9 %.
Claims (1)
- CLAIMS A process for the preparation of N-substituted pyrazoles of the general formula I wherein R 1 is C 1 -C 12 alkyl or C 7 -C 20 phenylalkyl and R 2 and R 4 are, independently from each other, hydrogen, C 1 -C 12 alkyl, C 7 -C 2 phenylalkyl or unsubstituted or substituted aryl radicals, by reaction of the pyrazoles of the general formula II. (ID, wherein R2, R3 and R4 have the meanings mentioned above, with an alcohol of the general formula III R'-OH (III), wherein R1 has the above-mentioned meaning, at 50-400 ° C in the presence of a catalyst, wherein the reaction of pyrazole II with compound III in the molar ratio from 0.001: 1 to 1: 1 is carried out in liquid phase under a pressure that is slightly below atmospheric or up to a pressure of 250 bar and acids and / or their alkyl esters or their anhydrides are used, in a molar ratio from 0.0001: 1 to 0.5: 1 with respect to pyrazole II, as a catalyst The process for the preparation of N-substituted pyrazoles of the formula I , according to claim 1, wherein sulfuric acid, alkyl sulfates, dialkyl sulfates, phosphoric acid, alkyl phosphates, alkylsulfonic acids or their alkyl esters, arylsulfonic acids or their alkyl esters and anhydrides are used as catalysts. from this acids such as sulfur trioxide or phosphorus pentoxide. The process for the preparation of N-substituted pyrazoles of formula I, according to claim 1, wherein the molar ratio of pyrazole II to compound III is from 0.002: 1 to 1: 1. The process for the preparation of N-substituted pyrazoles of formula I, according to claim 1, wherein the molar ratio of pyrazole II to compound III is from 0.003: 1 to 1: 1. The process for the preparation of N-substituted pyrazoles of formula I, according to claim 1, wherein the molar ratio of the catalyst to pyrazole II is from 0.0005: 1 to 0.5: 1. The process for the preparation of N-substituted pyrazoles of formula I, according to claim 1, wherein the molar ratio of the catalyst to pyrazole II is from 0.01: 1 to 0.2: 1. The process for the preparation of N-substituted pyrazoles of the formula I, according to claim 1, wherein the reaction is carried out at a pressure from 0.8 to 250 mbar. The process for the preparation of N-substituted pyrazoles of the formula I, according to claim 1, wherein the reaction is carried out at a pressure from 0.8 to 100 mbar. The process for the preparation of N-substituted pyrazoles of the formula I, according to claim 1, wherein the reaction is carried out at a pressure from 0.9 to 100 mbar. The process for the preparation of N-substituted pyrazoles of the formula I, according to claim 1, wherein the reaction is carried out at 100 to 350 ° C. SUMMARY OF THE INVENTION A process for the preparation of N-substituted pyrazoles of the general formula I wherein R1 is C1-C12alkyl or phenylalkyl of C7-Co and R2 and R4 are, independently from each other, hydrogen, C1-C12alkyl, C7-C2 phenylalkyl or unsubstituted or substituted aryl radicals, by the reaction of the pyrazoles of the general formula II. wherein R2, R3 and R4 have the meanings mentioned above, with an alcohol of the general formula III Rx-0-H (III), wherein R1 has the above-mentioned meaning, at 50-400 ° C in the presence of a catalyst , wherein the reaction of pyrazole II with compound III in the molar ratio from 0.001: 1 to 1: 1 is carried out in liquid phase under a pressure that is slightly below atmospheric or up to a pressure of 250 bar and they use acids and / or their alkyl esters or their anhydrides, in a molar ratio from 0.0001: 1 to 0.5: 1 with respect to pyrazole II, as a catalyst.
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19507600.1 | 1995-03-04 | ||
| DE19507600 | 1995-03-04 | ||
| DE1995109361 DE19509361A1 (en) | 1995-03-15 | 1995-03-15 | Prepn. of N-(phenyl)alkyl-pyrazole or deriv., useful as intermediate |
| DE19509361.5 | 1995-03-15 | ||
| DE1995109958 DE19509958A1 (en) | 1995-03-18 | 1995-03-18 | Prepn. of N-(phenyl)alkyl-pyrazole or deriv., useful as intermediate |
| DE19509958.3 | 1995-03-18 | ||
| PCT/EP1996/000790 WO1996027589A1 (en) | 1995-03-04 | 1996-02-27 | Process for preparing n-substituted pyrazoles |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| MX9706651A MX9706651A (en) | 1997-11-29 |
| MXPA97006651A true MXPA97006651A (en) | 1998-07-03 |
Family
ID=
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