MXPA00012504A - Procedure for producing formyl imidazoles - Google Patents
Procedure for producing formyl imidazolesInfo
- Publication number
- MXPA00012504A MXPA00012504A MXPA/A/2000/012504A MXPA00012504A MXPA00012504A MX PA00012504 A MXPA00012504 A MX PA00012504A MX PA00012504 A MXPA00012504 A MX PA00012504A MX PA00012504 A MXPA00012504 A MX PA00012504A
- Authority
- MX
- Mexico
- Prior art keywords
- process according
- further characterized
- catalytic oxidation
- catalyst
- alkaline medium
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 14
- XYHKNCXZYYTLRG-UHFFFAOYSA-N 1H-imidazole-2-carbaldehyde Chemical class O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 title abstract 3
- 230000003197 catalytic Effects 0.000 claims abstract description 9
- 150000002978 peroxides Chemical class 0.000 claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 3
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical group [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 16
- 239000003054 catalyst Substances 0.000 claims description 13
- 229910000510 noble metal Inorganic materials 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 230000003647 oxidation Effects 0.000 claims description 8
- 238000007254 oxidation reaction Methods 0.000 claims description 8
- MHAJPDPJQMAIIY-UHFFFAOYSA-N hydrogen peroxide Chemical group OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 7
- 229910052697 platinum Inorganic materials 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 6
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 claims description 5
- 229910052797 bismuth Inorganic materials 0.000 claims description 5
- -1 alkali metal acetate Chemical class 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 claims description 2
- 239000011541 reaction mixture Substances 0.000 claims description 2
- 239000000126 substance Substances 0.000 abstract description 2
- RRTJBIJAUFOAGW-UHFFFAOYSA-N 2-methyl-1H-imidazol-5-ol Chemical class CC1=NC=C(O)N1 RRTJBIJAUFOAGW-UHFFFAOYSA-N 0.000 abstract 1
- 238000006555 catalytic reaction Methods 0.000 abstract 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
- ZOMATQMEHRJKLO-UHFFFAOYSA-N 1H-imidazol-2-ylmethanol Chemical class OCC1=NC=CN1 ZOMATQMEHRJKLO-UHFFFAOYSA-N 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N DMSO-d6 Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- GLVYLTSKTCWWJR-UHFFFAOYSA-N 2-carbonoperoxoylbenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1C(O)=O GLVYLTSKTCWWJR-UHFFFAOYSA-N 0.000 description 1
- 229940030600 ANTIHYPERTENSIVES Drugs 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 229910052684 Cerium Inorganic materials 0.000 description 1
- RWGFKTVRMDUZSP-UHFFFAOYSA-N Cumene Chemical compound CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 description 1
- 229940030606 DIURETICS Drugs 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N Meta-Chloroperoxybenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 1
- RSPISYXLHRIGJD-UHFFFAOYSA-N OOOO Chemical compound OOOO RSPISYXLHRIGJD-UHFFFAOYSA-N 0.000 description 1
- XCRBXWCUXJNEFX-UHFFFAOYSA-N Peroxybenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1 XCRBXWCUXJNEFX-UHFFFAOYSA-N 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N TiO Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- MCMNRKCIXSYSNV-UHFFFAOYSA-N ZrO2 Chemical compound O=[Zr]=O MCMNRKCIXSYSNV-UHFFFAOYSA-N 0.000 description 1
- YAIQCYZCSGLAAN-UHFFFAOYSA-N [Si+4].[O-2].[Al+3] Chemical compound [Si+4].[O-2].[Al+3] YAIQCYZCSGLAAN-UHFFFAOYSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminum Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 230000001396 anti-anti-diuretic Effects 0.000 description 1
- 230000003276 anti-hypertensive Effects 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 125000004429 atoms Chemical group 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000004432 carbon atoms Chemical group C* 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- GWXLDORMOJMVQZ-UHFFFAOYSA-N cerium Chemical compound [Ce] GWXLDORMOJMVQZ-UHFFFAOYSA-N 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000005712 crystallization Effects 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atoms Chemical group [H]* 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N oxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 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
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 229910001929 titanium oxide Inorganic materials 0.000 description 1
- 229910001928 zirconium oxide Inorganic materials 0.000 description 1
Abstract
A new procedure for the catalytic conversion of hydroxy methyl imidazoles to formyl imidazoles is described. The catalysis takes place in the presence of a peroxide. Formyl imidazoles are important intermediate products for pharmaceutical substances.
Description
PROCEDURE FOR THE DEVELOPMENT OF FORMI IMIDAZOLES
DESCRIPTIVE MEMORY
This invention relates to a new process for the preparation of formylimidazoles of the general formula
wherein R1 represents an alkyl group, by catalytic oxidation of hydroxymethylimidazoles of the general formula
in an alkaline medium, in which R1 has the aforementioned meaning. Formylimidazoles are important intermediates, for example, for the production of pharmaceutical substances such as diuretics or antihypertensives (WO-A 92/20651). Previous processes have been known for the preparation of formylimidazoles. In CH-A 685496, a process is described in which the catalytic oxidation of hydroxymethylimidazoles or formylimidazoles is carried out in the presence of noble metal catalysts such as platinum / bismuth, platinum black, platinum or palladium on activated carbon, with insufflation of oxygen. Therefore, the task of the invention was to achieve the availability of an economical and improved process for the preparation of formylimidazoles. In this invention, this task was solved by means of the method defined in claim 1. In claim 1, the hydroxymethylimidazoles of the general formula
wherein R 1 signifies the aforementioned, are catalytically oxidized in an alkaline medium in the presence of a noble metal catalyst and a peroxide for formylimidazoles of the general formula
where R1 has the meaning mentioned above. R1 represents a hydrogen or an alkyl group, or more particularly a straight or branched chain alkyl group with 1 to 6
atoms C. Specifically, this may be methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl and its isomers as well as hexyl and its isomers. The preferred meaning of R1 is butyl. The hydroxymethylimidazoles can be easily processed as starting compounds as specified, for example, in WO-A 92/20651 or
as in E.F. Godefroi e tal., Trav. Chim Recueil Pays Bas, 91 .. 1383 (1972). Platinum, palladium, rhodium, or gold can be used as a noble metal catalyst. The noble metal is best used in combination with metals such as, for example, bismuth, lead, cerium or indium as the second component. The preferred catalysts are platinum / bismuth or
platinum / lead. The noble metal catalyst is used by itself or is attached to a vehicle such as, for example, activated carbon, silicon dioxide,
jai.M.MÍMli, i, l, i, l, M - ^ - Í-MÍIÍ-ÍÉ ------------ Ml ^^ rt T n aluminum, silicon-aluminum oxide, oxide of zirconium or titanium oxide. It binds preferably to activated carbon. The noble metal catalysts bound to activated carbon can be obtained commercially, for example, from Degussa. The appropriate percentage of the noble metal bound to a vehicle is between 0.1 to 15% by weight, and preferably between 0.5 and 7% by weight, in relation to the carrier material. Preferably, the noble metal catalyst is used in an amount of 0.05 to 1.0 mole% of noble metal base relative to 10-hydroxymethylimidazole, and an amount of 0.1 to 0.4 mole of noble metal base in particular is especially preferred. with hydroxymethylimidazole. Organic or inorganic peroxides are used as peroxides. For example, hydrogen peroxide, perborates, a percarboxylic acid, tert-butyl hydroperoperoxide, cumol hydroxyperoxide, perbenzoic acid, m-chloroperbenzoic acid, monoperphthalic acid or peracetic acid are suitable. Particularly suitable is hydrogen peroxide used in an aqueous solution in 10% to 30%. In addition to the catalytic oxidation, the hydrolysis of the methyl ester of hydroxymethylimidazoles of the general formula II takes place in an alkaline medium. The alkaline medium is best obtained by the addition of an alkali metal hydroxide, an alkali metal carbonate or an alkali metal acetate to the reaction mixture. The alkali metal hydroxide is
~~ - ^ ^ "....,. ... ^^ ufa. ^, ^. .. -rfÍ-fc-JtotAa "- '"' ** "» '• "• - - • •" &"; - &" - "M used preferably in a ratio of 1: 0.05 to 5 and still better in a ratio of 1: 3, relative to the molar amount used of the hydroxymethylimidazole of the general formula II. The catalytic oxidation takes place in better form in an alkaline medium in the presence of water, a solvent miscible in water or mixtures thereof. Particularly suitable miscible solvents in water are, for example, alcohols or carboxylic acids with 1 to 6 C atoms or ketones such as, for example, acetone or methyl ethyl ketone. Preferably mixtures of water and water miscible solvents are used. Catalytic oxidation is best carried out at a temperature of 20 ° to 120 ° C, preferably 50 ° to 100 ° C. After the standard peroxide dosing time of 0.5 to 3 hours, the compound of the general formula I can be isolated in the standard form after a sufficient secondary duration time. The product is isolated by crystallization and adequate filtration. The catalyst used can be reused several times without loss of activity.
** - ** -'- • * - • - *** - - • •• áM ^ ÉÍIF? IlMtÉ ^ M EXAMPLES
EXAMPLE 1 Production of 4-r (2-butyl-5-formyl-1 H-imidazo-1-yl) methanolbenzoic acid
900 mg (3 mmol) of 4 - [(2-butyl-5-hydroxymethyl-1 H-imidazo-1-yl) methyl] benzoic acid methyl ester, 8 ml of caustic soda solution
(1 M), 0.5 ml of methanol and 107 mg of 5% platinum and 5% bismuth on activated carbon containing 60% water are placed in a 25 ml flask at room temperature and heated to 60 ° C. 0.8 g (4.6 mmol) 20% of an aqueous H 2 O 2 solution was added to this suspension at 60 ° C for 30 minutes and the mixture was then reacted with HPLC. Another 0.2 g (1.1 mmol) aqueous solution to 20% H2O2 were then added for 10 minutes. Then 0.2 g (5 mmoles) of 20% NaOH was added. The reaction solution was heated for 2 hours at 100 ° C. The mixture was cooled to room temperature.
The catalyst was filtered over celite and washed with 5 ml of water. After acidification of pH 5.0 with HCl (15%), the product was precipitated. It cooled to
2 ° C, it was filtered, washed with 2 x 5 ml of water and dried at room temperature at 15 mbar. 410 mg (48%) of yellow 4 - [(2-butyl-5-formyl-1 H-imidazo-1-yl) methyl] benzoic acid (96% content by HPLC) was obtained. Melting point: 144-146 ° C.
^ Mu M mi 1H NMR (DMSO-d6, 400 MHz) d 12.9 (1H, s), 9.65 (1H, s), 7.94 (1H, s), 7.90 (2H, d), 7.11 (2H, d) , 565 (2H, s), 2.63 (2H, t), 1.54 (2H, pent), 1.36 (2H, hex), 0.79 (3H, t).
í ^^^^^^^ - --- ^ a ^ l? ^^ - ^ - ^^^^^^^^ l ^^^^ í?
Claims (7)
1. - A process for the preparation of formylimidazoles of the general formula wherein R1 represents an alkyl group, by the catalytic oxidation of hydroxymethyldimidazoles of the general formula 3 in which R1 has the above-mentioned meaning, in the presence of a noble metal catalyst, characterized in that the catalytic oxidation takes place in the presence of a peroxide in an alkaline medium. g »- *! ^ £ ^ g
2. The process according to claim 1, further characterized in that R1 is a butyl group.
3. The process according to any of claims 1 or 2, further characterized in that the noble metal catalyst is a platinum / bismuth catalyst or a platinum / lead catalyst.
4. The process according to any of claims 1 to 3, further characterized in that the peroxide is hydrogen peroxide.
5. The process according to any of claims 1 to 4, further characterized in that the alkaline medium was obtained by the addition of an alkali metal hydroxide, an alkali metal carbonate or an alkali metal acetate to the reaction mixture .
6. The process according to any of claims 1 to 5, further characterized in that the catalytic oxidation was carried out in the presence of water, a solvent miscible with water, or a mixture thereof, in an alkaline medium.
7. The process according to any of claims 1 to 6, further characterized in that the reaction was carried out at a temperature of 20 ° to 120 ° C.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP98110868.1 | 1998-06-15 |
Publications (1)
Publication Number | Publication Date |
---|---|
MXPA00012504A true MXPA00012504A (en) | 2001-11-21 |
Family
ID=
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6258958B1 (en) | Procedure for producing formyl imidazoles | |
MXPA00012504A (en) | Procedure for producing formyl imidazoles | |
KR100587187B1 (en) | Process for the preparation of formylimidazoles | |
CN114835645A (en) | Preparation method of 6-chloro-2-methyl-2H-indazole-5-amine | |
JP4418104B2 (en) | Formylimidazole production process | |
US6469178B2 (en) | Procedure for producing formylimidazoles | |
MXPA00004736A (en) | Process for the production of formylimidazoles | |
CA2253901C (en) | Process for the preparation of formylimidazoles | |
JP4066100B2 (en) | Process for producing N-acyl nitrogen-containing cyclic ketones | |
CZ20001764A3 (en) | Process for preparing formylimidazoles | |
JPH06192169A (en) | Production of dimethylolalkanoic acid | |
CZ20004664A3 (en) | Process for preparing formylimidazoles | |
JP2002308853A (en) | Production method for 2-formylimidazole and its intermediate | |
JPH0446167A (en) | Production of 2-furancarboxylic acid |