U.S. patent application number 09/820394 was filed with the patent office on 2001-08-16 for procedure for producing formylimidazoles.
This patent application is currently assigned to Lonza AG. Invention is credited to Bessard, Yves, Heveling, Josef.
Application Number | 20010014743 09/820394 |
Document ID | / |
Family ID | 27173818 |
Filed Date | 2001-08-16 |
United States Patent
Application |
20010014743 |
Kind Code |
A1 |
Bessard, Yves ; et
al. |
August 16, 2001 |
Procedure for producing formylimidazoles
Abstract
A new process for the catalytic conversion of hydroxymethyl
imidazoles to formylimidazoles is described. The reaction takes
place in the presence of a peroxide. Formylimidazoles are important
intermediate products for pharmaceutical substances.
Inventors: |
Bessard, Yves; (Sierre,
CH) ; Heveling, Josef; (Naters, CH) |
Correspondence
Address: |
GLAXOSMITHKLINE
Corporate Intellectual Property - UW2220
P.O. Box 1539
King of Prussia
PA
19406-0939
US
|
Assignee: |
Lonza AG
|
Family ID: |
27173818 |
Appl. No.: |
09/820394 |
Filed: |
March 29, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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09820394 |
Mar 29, 2001 |
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09554308 |
May 11, 2000 |
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09554308 |
May 11, 2000 |
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PCT/EP98/07322 |
Nov 10, 1998 |
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Current U.S.
Class: |
548/341.1 |
Current CPC
Class: |
C07D 233/64
20130101 |
Class at
Publication: |
548/341.1 |
International
Class: |
C07D 233/64 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 14, 1997 |
CH |
2638/97 |
Nov 27, 1997 |
CH |
2738/97 |
Claims
1. A process for producing formylimidazoles of the formula (I): 5in
which R.sup.1 is C.sub.1-6alkyl, which comprises catalytic
oxidation of hydroxymethyl imidazoles of the general formula (II):
6in which R.sup.1 is as defined above, in the presence of a noble
metal catalyst, wherein the catalytic oxidation takes place in the
of a peroxide.
2. The process according to claim 1 wherein R.sup.1 is butyl.
3. The process according to claims 1 or 2 wherein the noble metal
catalyst is a platinum/bismuth catalyst or a platinum/lead
catalyst.
4. The process according to claims 1 to 3 wherein the peroxide is
hydrogen peroxide.
5. The process according to claims 1 to 4 wherein the catalytic
oxidation is performed in the presence of water, a water-miscible
solvent or mixtures thereof, in an alkaline medium.
6. The process according to claim 5 wherein the alkaline medium is
obtained by adding an alkali hydroxide, an alkali carbonate or an
alkali acetate to the reaction mixture.
7. The process according to claims 1 to 6 wherein the reaction is
performed at a temperature of 20.degree.-120.degree. C.
Description
[0001] This invention concerns a new procedure for producing formyl
imidazoles of the general formula 1
[0002] in which R.sup.1 means an alkyl group, by catalytic
oxidation of hydroxy methyl imidazoles of the general formula 2
[0003] in which R.sup.1 has the meaning given above.
[0004] Formyl imidazoles are important intermediate products, for
example, for the production of pharmaceutical substances such as
diuretics or antihypertensives (WO-A 92/20651). Several procedures
have previously been known for producing formyl imidazoles. In CH-A
685496, a procedure is described in which the catalytic oxidation
of hydroxy methyl imidazoles to formyl imidazoles is performed in
the presence of noble metal catalysts such as platinum bismuth,
platinum black, platinum or palladium on activated charcoal with
oxygen insufflation.
[0005] The task of the invention was therefore to make available an
economical, improved procedure for producing formyl imidazoles.
[0006] In this invention, this task is solved by the procedure
defined in claim 1.
[0007] In claim 1, hydroxy methyl imidazoles of the general formula
3
[0008] in which R.sup.1 has the meaning given above, are
catalytically oxidized in the presence of a noble metal catalyst
and a peroxide to formyl imidazoles of the general formula 4
[0009] in which R.sup.1 has the meaning given above.
[0010] R.sup.1 has the meaning of hydrogen or an alkyl group, and
more particularly a straight-chained or ramified alkyl group with 1
to 6 C atoms. 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 R.sup.1 is
butyl.
[0011] Hydroxy methyl imidazoles can be readily produced as
starting compounds as specified, for example, in WO-A 92/20651 or
in E. F. Godefroi et al., Trav. Chim. Receuil Pays-Bas, 91, 1383
(1972).
[0012] Platinum, palladium, rhodium or gold can be used as the
noble metal catalyst. The noble metal is appropriately used in
combination with metals such as, for example, bismuth, lead, cenum
or indium as the second component. The preferred catalysts are
platinum/bismuth or platinum/lead.
[0013] The noble metal catalyst is used by itself or bound to a
vehicle such as, for example, activated charcoal, silicon dioxide,
aluminum dioxide, silicon-aluminum dioxide, zirconium oxide or
titanium oxide. It is preferably bound to activated charcoal.
[0014] Noble metal catalysts bound to activated charcoal can be
commercially obtained, for example, from Degussa.
[0015] The appropriate percentage of the noble metal bound to a
vehicle is between 0.1 and 15% by weight, and preferably between
0.5 and 7% by weight, relative to the vehicle material.
[0016] The noble metal catalyst is preferably used in an amount of
0.05 to 1.0 mol % noble metal base relative to hydroxy methyl
imidazole, and an amount of 0.1 to 0.4 mol % noble metal base
relative to hydroxy methyl imidazole is especially preferred.
[0017] Organic or inorganic peroxides are used as peroxides.
Hydrogen peroxide, perborates, a percarboxylic acid, tert-butyl
hydroperoxide, cumol hydroperoxide, perbenzoic acid,
m-chloroperbenzoic acid, monoperphthalic acid or peracetic acid are
well suited, for example. Hydrogen peroxide used in a 10% to 30%
aqueous solution is particularly suitable.
[0018] The catalytic oxidation takes place appropriately in the
presence of water, a water-miscible solvent or mixtures thereof, in
an alkaline milieu.
[0019] Particularly suitable water-miscible solvents are, for
example, alcohols or carboxylic acids with 1 to 6 C atoms or
ketones such as, for example, acetone or methyl ethyl ketone.
[0020] Mixtures of water and water-miscible solvents are preferably
used. It has proven to be advantageous if the water used is
adjusted to be alkaline, by the appropriate addition of an alkali
hydroxide, an alkali carbonate or an alkali acetate. Alkali
hydroxide is preferably used in the ratio 1:0.05 to 5, and
preferably 1:1 to 3, relative to the mol amount used of the hydroxy
methyl imidazole of general formula II.
[0021] The catalytic oxidation is appropriately performed at a
temperature of 20.degree. to 120.degree. C., preferably at
50.degree.-80.degree. C.
[0022] After the standard peroxide dosing time of 2-3 hours, the
compound of general formula I can be isolated in the standard
manner after a sufficient secondary reaction time.
[0023] The product is isolated by appropriate crystallization and
filtration. The catalyst used can be used several times with no
loss of activity.
EXAMPLES
Example 1
Production of 4-[(2-butyl-5-formyl-1H-imidazo-1-yl)methyl]benzoic
Acid
[0024] 9.5 g (33 mmol)
4-[(2-butyl-5-hydroxymethyl-1H-imidazo-1-yl)methyl]- benzoic acid,
40 ml water, 10 ml methanol, 4.2 g (105 mmol) NaOH and 0.92 g 5%
platinum and 5% bismuth on activated charcoal (containing 60%
water) are placed in a 100-ml flask at room temperature and heated
to 60.degree. C. 6.6 g (39 mmol) 20% aqueous H.sub.2O.sub.2
solution were added to this suspension at 60.degree. C. over 60
minutes and the mixture was then converted with HPLC. 6.6 g (39
mmol) 20% aqueous H.sub.2O.sub.2 solution were again added over 60
minutes. 1.7 g (10 mmol) 20% aqueous H.sub.2O.sub.2 solution were
then added over 20 minutes (conversion>90%). The mixture was
cooled to room temperature. After acidification to pH 6.0 with 17.6
ml HCl (15%), the product was preciptated. It was cooled to
2.degree. C., filtered, washed with 2.times.20 ml water, and dried
at room temperature at 15 mbar. 7.2 g (70%) of yellow
4-[(2-butyl-5-formyl-1H-imidazo-1-yl)methyl]benzoic acid (HPLC
content 95%) were obtained.
[0025] Melting point: 144-146.degree. C.
[0026] .sup.1H-NMR (DMSO-.sub.d6, 400 MHz).delta.:
[0027] 12.9 (1 H, s);
[0028] 9.65 (1 H, s);
[0029] 7.94 (1 H, s);
[0030] 7.90 (2 H, d);
[0031] 7.11 (2 H, d);
[0032] 5.65 (2 H, s);
[0033] 2.63 (2 H, t);
[0034] 1.54 (2 H, pent);
[0035] 1.36 (2 H, hex);
[0036] 0.79 (3 H, t).
* * * * *