Indian Patents. 268734:A PROCESS FOR THE PREPARATION OF 1,4-DIALKYL-2,3-DIOL-1,4-BUTANEDIONE

Title of Invention	A PROCESS FOR THE PREPARATION OF 1,4-DIALKYL-2,3-DIOL-1,4-BUTANEDIONE
Abstract	The present invention relates to a process for the preparation of compounds of a 1,4-dialkyl-2,3-diol-1,4-butanedione by a acidic aldol condensation between an alkyl glyoxal and an α-hydroxy ketone.

Full Text	A PROCESS FOR THE PREPARATION OF 1.4-DIALKYL-2,3-DIOL-1,4- BUTANEDIONE Technical field The present invention relates to the field of organic synthesis and more particularly to a process for the preparation of compounds of formula (I) by the aldol condensation between an alkyl glyoxal (II) and an acetol derivative (III), said condensation being promoted by specific acidic conditions, according to Scheme (1): Scheme 1: aldol condensation of glyoxals and acetols according to the invention wherein R1 represents a linear or branched C1 to C5 alkyl group. Prior art The compounds of formula (I), as defined below, can be useful as starting material for the construction of compounds having a more complex skeleton, such as 4-hydroxy- 2,5-dimethyl-3(2H)-furanone (known as Furaneol®, Trademark of Firmenich SA). Various processes for the preparation of compounds of formula (I) have been reported, for example Briggs et al, J. Chem. Soc. Perkin. Trans. I, 1985, 795 relates to a multistep synthesis of the 3,4-dihydroxyhexane-2,5-dione starting from tartaric acid, or Bassignani et al, J Org. Chem., 1978, 43, 4245 relates to the synthesis of the 3,4-dihydroxyhexane-2,5-dione by oxidizing the expensive 2,5-dimethylfuran with the toxic and expensive KC103/OsO4 system. Another reported method to synthesize compounds (I) is the reductive dimerisation of glyoxals promoted by various methods (for instance see Buchi et al, J. Org. Chem., 1973, 38. 123). More recently, F.Naef and al. (WO 2006/048795) reported a method of preparation by aldol condensation between an alkyl glyoxal and an acetol derivative, this method requiring the mandatory presence of specific catalysts, such as Zn(AcO)2. The reported method suffers from relatively low yields and the mandatory use of metal salts as catalysts, as well as from very long reaction times. The above-mentioned methods of preparation are in general quite long and expensive or require the use of a heavy metal which implies problems of purification of the final product and of waste treatment. Furthermore, frequently the yields are low. Therefore, there is still a need for a method of preparation that is more environmental friendly, more direct or fast and providing good yields. Description of the invention In order to overcome the problems aforementioned, and provide also an alternative process for the preparation of compounds of formula (I), the present invention relates to a process aimed at the synthesis of compounds (I) in a single step and with good yields. The process of the invention concerns more specifically the aldol condensation between an alkyl glyoxal (II) and an acetol derivative (III) under acidic condition without requiring the mandatory presence of a metal salt, contrary to the prior art aldol process. Therefore, the process of the invention concerns the preparation of a compound of formula wherein each R1 represents, simultaneously or independently from each other, a linear or branched C1to C5 alkyl group, by the aldol condensation, in an aqueous reaction medium, between a glyoxal of formula wherein R1 has the same meaning as defined above, and an a-hydroxy ketone of formula wherein Rl has the same meaning as defined above, said process being characterized in that said aqueous reaction medium has a pH comprised between 0 and 6, and that the process is carried out at a temperature comprised between 50°C and the reflux temperature. The invention's process does not require metal catalysts, and therefore can be carried out in the absence of such compounds. In particular the catalysts of formula FeX3 or MX2, wherein M is Zn2+, Mg2+, Cu2+, Fe2+ or Ca2+ and X is a C1-C7 carboxylate, a halide or an acetylacetonate derivative of formula [R2COCHCOR2]-, R2 representing a C1-C3 alkyl group or a phenyl group, as described in WO 2006/048795 are not required. According to particular embodiment of the invention, said process can be also free of any useful amount of catalysts of formula M(X)n, wherein n is 2 or 3, X is as defined above and M is a transition or alkaline-earth metal. As mentioned above the process takes place within a specific pH range of the aqueous reaction medium, i.e. form a weakly acidic to strong acidic medium. According to an embodiment of the invention the present process is preferably carried out in a reaction medium having a pH comprised between 0 and 4.6, preferably between 0.0 and 3.0, or even comprised between 0.5 and 2.3. The pH can be set up to the desired value by adding into the reaction medium an acid or a base, in such a case the pH of the medium once fixed may change within the desired range during the reaction. Mixtures of acids can also be used. Alternatively, the pH of the medium can be regulated and maintained throughout the reaction by using a buffer. It is useful also to note here that an aqueous reaction medium consisting of water and compounds (II) and (III), is as such already acidic and therefore in some case it may not be necessary to add an acid to acidify the aqueous reaction medium, but rather it may be necessary to add a base to increase the pH to the desired value. Any type of acid can be used, i.e. organic, inorganic or acidic resin. Such acids are well known by a parson skilled in the art. As typical examples, one may cite the following: HCl, H2SO4, H3PO4, C1-C7 sulphonic acids (e.g. MeC6H4SO3H, MeSO3H, CF3SO3H), C1-C7 carboxylic acids (e.g. C6H5COOH, CH3COCOOH, CH3COOH, C2H5COOH) and the acidic resins such as the carboxylic or sulphonic acid supported on a methacrylic based or styrene based matrix (e.g. the one known under the tradenames Dowex® 50x8 or Amberlite® ICR 50). According to a particular embodiment of the invention, said acid is a carboxylic derivative as described above. As a base, to adjust the pH or to generate a buffer, typically an alkaline hydroxide such as NaOH or KOH, or an alkaline carbonate or bicarbonate such as Na2CO3 or NaHCO3, may be used. For the sake of clarity, by "aqueous reaction medium" it is meant here the medium wherein the reaction takes place. Therefore, the aqueous reaction medium comprises, or preferably consists of: - water and optionally a fully miscible solvent, - an appropriate amount of at least an acid or a base or of a mixture thereof, such as a buffer; - the compounds of formula (II) and (III), and optionally (I). According to a particular embodiment of the invention, said aqueous reaction medium may comprise at least 10% of water, preferably at least 15% or even more between 20% and 60% of water, percentage being relative to its own weight. The above- mentioned fully miscible solvent may be present in amount ranging between 0% and 100%, percentage being relative to the weight of water. Typical examples of such solvents are tetrahydrofuran (THF), or a lower alcohol such as methanol, ethanol or a propanol. According to a particular embodiment of the invention, both Rl groups have the same meaning. According to a further embodiment both R1 groups represent a methyl group and therefore the glyoxal (II) is methyl glyoxal. the acetol (III) is acetol (i.e. l-hydroxy-2-propanone) and the dihydroxy-dione (I) is 3,4-dihydroxyhexane-2,5-dione. The amount in which the acetol derivative (III) may be employed in the invention's process is typically comprised between 0.5 and 20 molar equivalents, relative to the glyoxal. According to a particular embodiment said amount may range from 2 to 10 molar equivalents, relative to the glyoxal. The temperature at which the process of the invention can be carried out is comprised between 50°C and 120°C, more preferably between 65°C and 95°C. If necessary, the reaction can also be carried out in the presence of pressure, so as to react the higher temperature of the described ranges. As mentioned above, the compound of formula (I) can be a valuable intermediate for the preparation of furanone derivatives and in particular, when R1 and R2 are both a methyl group, for the preparation of the flavor ingredient 4-hydroxy-2,5-dimethyl-3(2H)- furanone. Therefore another object of the present invention is a process for the preparation of a furanone of formula comprising the following steps: - the preparation of a compound (I), as defined hereinabove, according to a process as described in the present invention; and - the cyclisation of said compound (I). The cyclisation step can be performed according to any method known to a person skilled in the art. For example, one may cite a cyclisation method in the presence of a buffer such the ones described by Buchi et al. in J.Org.Chem, 1973, 123, or by Selinov et al. in US2002/0111500, or by Briggs et al/. in J.Chem.Soc. Perkin Trans. 1,1985, 795. Examples The invention will now be described in further detail by way of the following examples, wherein the temperatures are indicated in degrees centigrade and the abbreviations have the usual meaning in the art. Example 1 Experimental procedure A solution of methyl glyoxal 43% wt in water (2.00 g, 11.9 mmol), hydroxy-acetone (4.42 g, 59.7 mmol), and acetic acid (1.43 g, 23.8 mmol) in water (0.9 ml) were stirred during 16 hours at 70° C (pH of the reaction medium was around 2.0). At the end of the reaction the reaction mixture was concentrated under reduced pressure giving 2.1 g of the crude 3,4-dihydroxyhexane-2,5-dione (56% purity measured by GC vs. internal standard). Crude 3,4-dihydroxyhexane-2,5-dione was distilled under reduced pressure to give 3,4-dihydroxyhexane-2,5-dione (1.56g, 74% purity, 66% yield) as a pale yellow solid. The product obtained had the same 1H-NMR spectra as those described in Buchi et al J.Org.Chem., 1973, 38, 123. Following the same experimental procedure as above several other experiments according to the invention were performed. The results are summarized in the Table 1. Table 1; Aldol condensation between methyl glyoxal and Acetol to give 3,4- dihydroxyhexane-2,5-dione m.e. = molar equivalent; 1) acid or buffer used to fix the pH of the reacting medium, amounts relative to methyl glyoxal 2) comparative examples performed in the presence of Zn(acac)2 at 0.08 m.e. (according to Example 1, Table 1, N°2 in WO 2006/048795) 3) comparative examples performed in the presence of Zn(acetate)2 at 0.10 m.e., acid used is AcOH, (according experimental conditions described in WO 2006/048795) Claims 1. A process for the preparation of a compound of formula wherein each R1 represents, simultaneously or independently from each other, a linear or branched C1 to C5 alkyl radical, by the aldol condensation, in an aqueous reaction medium, between a glyoxal of formula wherein R1 has the same meaning as defined above, and an a-hydroxy ketone of formula wherein R1 has the same meaning as defined above, said process being characterized in that said aqueous reaction medium has a pH comprised between 0 and 6, and that the process is carried out at a temperature comprised between 50°C and the reflux temperature; provided that the presence of catalysts of formula FeX3 or MX2. wherein M is Zn2+, Mg2+, Cu2+, Fe2+ or Ca2+ and X is a C1-C7 carboxylate,. a halide or an acetylacetonate derivative of formula [R'COCHCOR], R~ representing a C1-C3 alkyl group or a phenyl group, is excluded. 2. A process according to claim 1, characterized in that it is free of any useful amount of catalysts of formula M(X)n, wherein n is 2 or 3, X is as defined in claim 1 and M is a transition or alkaline-earth metal. 3. A process according to claim 1 or 2, characterized in that said aqueous reaction medium has a pH comprised between 0 and 4.6. 4. A process according to any one of claims 1 to 4, characterized in that the process is carried out at a temperature comprised between 65°C and 95°C. 5. A process according to any one of claims 1 to 4, characterized in that the pH of said aqueous reaction medium comprises an appropriate amount of at least an acid or a base or of a mixture thereof, to regulate the pH. 6. A process according to claim 5, characterized in that said acid is HC1, H2SO4, H3PO4, C1-C7 sulphonic acids (e.g. MeC6H4SO3H, MeSO,H, CF3SO3H), C1-C7 carboxylic acids (e.g. C6H5COOH, CH3COCOOH, CH3COOH, C2H5COOH) and the carboxylic or sulphonic acid resins. 7. A process according to claim 5 or 6, characterized in that said base is an alkaline hydroxide or an alkaline carbonate or bicarbonate. 8. A process according to any one of claims 1 to 7, characterized in that each R1 represents a methyl group. 9. A process for the preparation of a furanone of formula comprising: - the preparation of a compound (I), as defined in any one of claims 1 to 8, by a process according to any one of claims 1 to 8; and - the cyclisation of said compound (I). The present invention relates to a process for the preparation of compounds of a 1,4-dialkyl-2,3-diol-1,4-butanedione by a acidic aldol condensation between an alkyl glyoxal and an α-hydroxy ketone.

Full Text

A PROCESS FOR THE PREPARATION OF 1.4-DIALKYL-2,3-DIOL-1,4-
BUTANEDIONE
Technical field
The present invention relates to the field of organic synthesis and more
particularly to a process for the preparation of compounds of formula (I) by the aldol
condensation between an alkyl glyoxal (II) and an acetol derivative (III), said
condensation being promoted by specific acidic conditions, according to Scheme (1):
Scheme 1: aldol condensation of glyoxals and acetols according to the invention

wherein R1 represents a linear or branched C1 to C5 alkyl group.
Prior art
The compounds of formula (I), as defined below, can be useful as starting material
for the construction of compounds having a more complex skeleton, such as 4-hydroxy-
2,5-dimethyl-3(2H)-furanone (known as Furaneol®, Trademark of Firmenich SA).
Various processes for the preparation of compounds of formula (I) have been
reported, for example Briggs et al, J. Chem. Soc. Perkin. Trans. I, 1985, 795 relates to a
multistep synthesis of the 3,4-dihydroxyhexane-2,5-dione starting from tartaric acid, or
Bassignani et al, J Org. Chem., 1978, 43, 4245 relates to the synthesis of the
3,4-dihydroxyhexane-2,5-dione by oxidizing the expensive 2,5-dimethylfuran with the
toxic and expensive KC103/OsO4 system. Another reported method to synthesize
compounds (I) is the reductive dimerisation of glyoxals promoted by various methods (for
instance see Buchi et al, J. Org. Chem., 1973, 38. 123).
More recently, F.Naef and al. (WO 2006/048795) reported a method of
preparation by aldol condensation between an alkyl glyoxal and an acetol derivative, this
method requiring the mandatory presence of specific catalysts, such as Zn(AcO)2. The
reported method suffers from relatively low yields and the mandatory use of metal salts as
catalysts, as well as from very long reaction times.
The above-mentioned methods of preparation are in general quite long and
expensive or require the use of a heavy metal which implies problems of purification of
the final product and of waste treatment. Furthermore, frequently the yields are low.
Therefore, there is still a need for a method of preparation that is more
environmental friendly, more direct or fast and providing good yields.
Description of the invention
In order to overcome the problems aforementioned, and provide also an
alternative process for the preparation of compounds of formula (I), the present invention
relates to a process aimed at the synthesis of compounds (I) in a single step and with good
yields.
The process of the invention concerns more specifically the aldol condensation
between an alkyl glyoxal (II) and an acetol derivative (III) under acidic condition without
requiring the mandatory presence of a metal salt, contrary to the prior art aldol process.
Therefore, the process of the invention concerns the preparation of a compound of
formula

wherein each R1 represents, simultaneously or independently from each other, a linear or
branched C1to C5 alkyl group,
by the aldol condensation, in an aqueous reaction medium, between a glyoxal of formula

wherein R1 has the same meaning as defined above,
and an a-hydroxy ketone of formula

wherein Rl has the same meaning as defined above,
said process being characterized in that said aqueous reaction medium has a pH
comprised between 0 and 6, and that the process is carried out at a temperature comprised
between 50°C and the reflux temperature.
The invention's process does not require metal catalysts, and therefore can be
carried out in the absence of such compounds. In particular the catalysts of formula FeX3
or MX2, wherein M is Zn2+, Mg2+, Cu2+, Fe2+ or Ca2+ and X is a C1-C7 carboxylate, a
halide or an acetylacetonate derivative of formula [R2COCHCOR2]-, R2 representing a
C1-C3 alkyl group or a phenyl group, as described in WO 2006/048795 are not required.
According to particular embodiment of the invention, said process can be also free of any
useful amount of catalysts of formula M(X)n, wherein n is 2 or 3, X is as defined above
and M is a transition or alkaline-earth metal.
As mentioned above the process takes place within a specific pH range of the
aqueous reaction medium, i.e. form a weakly acidic to strong acidic medium.
According to an embodiment of the invention the present process is preferably
carried out in a reaction medium having a pH comprised between 0 and 4.6, preferably
between 0.0 and 3.0, or even comprised between 0.5 and 2.3.
The pH can be set up to the desired value by adding into the reaction medium an
acid or a base, in such a case the pH of the medium once fixed may change within the
desired range during the reaction. Mixtures of acids can also be used. Alternatively, the
pH of the medium can be regulated and maintained throughout the reaction by using a
buffer.
It is useful also to note here that an aqueous reaction medium consisting of water
and compounds (II) and (III), is as such already acidic and therefore in some case it may
not be necessary to add an acid to acidify the aqueous reaction medium, but rather it may
be necessary to add a base to increase the pH to the desired value.
Any type of acid can be used, i.e. organic, inorganic or acidic resin. Such acids are
well known by a parson skilled in the art. As typical examples, one may cite the
following: HCl, H2SO4, H3PO4, C1-C7 sulphonic acids (e.g. MeC6H4SO3H, MeSO3H,
CF3SO3H), C1-C7 carboxylic acids (e.g. C6H5COOH, CH3COCOOH, CH3COOH,
C2H5COOH) and the acidic resins such as the carboxylic or sulphonic acid supported on a
methacrylic based or styrene based matrix (e.g. the one known under the tradenames
Dowex® 50x8 or Amberlite® ICR 50).
According to a particular embodiment of the invention, said acid is a carboxylic
derivative as described above.
As a base, to adjust the pH or to generate a buffer, typically an alkaline hydroxide
such as NaOH or KOH, or an alkaline carbonate or bicarbonate such as Na2CO3 or
NaHCO3, may be used.
For the sake of clarity, by "aqueous reaction medium" it is meant here the medium
wherein the reaction takes place. Therefore, the aqueous reaction medium comprises, or
preferably consists of:
- water and optionally a fully miscible solvent,
- an appropriate amount of at least an acid or a base or of a mixture thereof, such as a
buffer;
- the compounds of formula (II) and (III), and optionally (I).
According to a particular embodiment of the invention, said aqueous reaction
medium may comprise at least 10% of water, preferably at least 15% or even more
between 20% and 60% of water, percentage being relative to its own weight. The above-
mentioned fully miscible solvent may be present in amount ranging between 0% and
100%, percentage being relative to the weight of water. Typical examples of such
solvents are tetrahydrofuran (THF), or a lower alcohol such as methanol, ethanol or a
propanol.
According to a particular embodiment of the invention, both Rl groups have the
same meaning. According to a further embodiment both R1 groups represent a methyl
group and therefore the glyoxal (II) is methyl glyoxal. the acetol (III) is acetol (i.e.
l-hydroxy-2-propanone) and the dihydroxy-dione (I) is 3,4-dihydroxyhexane-2,5-dione.
The amount in which the acetol derivative (III) may be employed in the
invention's process is typically comprised between 0.5 and 20 molar equivalents, relative
to the glyoxal. According to a particular embodiment said amount may range from 2 to
10 molar equivalents, relative to the glyoxal.
The temperature at which the process of the invention can be carried out is
comprised between 50°C and 120°C, more preferably between 65°C and 95°C. If
necessary, the reaction can also be carried out in the presence of pressure, so as to react
the higher temperature of the described ranges.
As mentioned above, the compound of formula (I) can be a valuable intermediate
for the preparation of furanone derivatives and in particular, when R1 and R2 are both a
methyl group, for the preparation of the flavor ingredient 4-hydroxy-2,5-dimethyl-3(2H)-
furanone.
Therefore another object of the present invention is a process for the preparation
of a furanone of formula

comprising the following steps:
- the preparation of a compound (I), as defined hereinabove, according to a process as
described in the present invention; and
- the cyclisation of said compound (I).
The cyclisation step can be performed according to any method known to a person
skilled in the art. For example, one may cite a cyclisation method in the presence of a
buffer such the ones described by Buchi et al. in J.Org.Chem, 1973, 123, or by Selinov et
al. in US2002/0111500, or by Briggs et al/. in J.Chem.Soc. Perkin Trans. 1,1985, 795.
Examples
The invention will now be described in further detail by way of the following
examples, wherein the temperatures are indicated in degrees centigrade and the
abbreviations have the usual meaning in the art.
Example 1
Experimental procedure
A solution of methyl glyoxal 43% wt in water (2.00 g, 11.9 mmol), hydroxy-acetone
(4.42 g, 59.7 mmol), and acetic acid (1.43 g, 23.8 mmol) in water (0.9 ml) were stirred
during 16 hours at 70° C (pH of the reaction medium was around 2.0). At the end of the
reaction the reaction mixture was concentrated under reduced pressure giving 2.1 g of the
crude 3,4-dihydroxyhexane-2,5-dione (56% purity measured by GC vs. internal standard).
Crude 3,4-dihydroxyhexane-2,5-dione was distilled under reduced pressure to give
3,4-dihydroxyhexane-2,5-dione (1.56g, 74% purity, 66% yield) as a pale yellow solid.
The product obtained had the same 1H-NMR spectra as those described in Buchi et al
J.Org.Chem., 1973, 38, 123.
Following the same experimental procedure as above several other experiments
according to the invention were performed. The results are summarized in the Table 1.
Table 1; Aldol condensation between methyl glyoxal and Acetol to give 3,4-
dihydroxyhexane-2,5-dione
m.e. = molar equivalent;
1) acid or buffer used to fix the pH of the reacting medium, amounts relative to methyl
glyoxal
2) comparative examples performed in the presence of Zn(acac)2 at 0.08 m.e. (according
to Example 1, Table 1, N°2 in WO 2006/048795)
3) comparative examples performed in the presence of Zn(acetate)2 at 0.10 m.e., acid
used is AcOH, (according experimental conditions described in WO 2006/048795)
Claims
1. A process for the preparation of a compound of formula

wherein each R1 represents, simultaneously or independently from each other, a linear or
branched C1 to C5 alkyl radical,
by the aldol condensation, in an aqueous reaction medium, between a glyoxal of formula

wherein R1 has the same meaning as defined above,
and an a-hydroxy ketone of formula

wherein R1 has the same meaning as defined above,
said process being characterized in that said aqueous reaction medium has a pH
comprised between 0 and 6, and that the process is carried out at a temperature comprised
between 50°C and the reflux temperature; provided that the presence of catalysts of
formula FeX3 or MX2. wherein M is Zn2+, Mg2+, Cu2+, Fe2+ or Ca2+ and X is a C1-C7
carboxylate,. a halide or an acetylacetonate derivative of formula [R'COCHCOR], R~
representing a C1-C3 alkyl group or a phenyl group, is excluded.
2. A process according to claim 1, characterized in that it is free of any useful
amount of catalysts of formula M(X)n, wherein n is 2 or 3, X is as defined in claim 1 and
M is a transition or alkaline-earth metal.
3. A process according to claim 1 or 2, characterized in that said aqueous
reaction medium has a pH comprised between 0 and 4.6.
4. A process according to any one of claims 1 to 4, characterized in that the
process is carried out at a temperature comprised between 65°C and 95°C.
5. A process according to any one of claims 1 to 4, characterized in that the
pH of said aqueous reaction medium comprises an appropriate amount of at least an acid
or a base or of a mixture thereof, to regulate the pH.
6. A process according to claim 5, characterized in that said acid is HC1,
H2SO4, H3PO4, C1-C7 sulphonic acids (e.g. MeC6H4SO3H, MeSO,H, CF3SO3H), C1-C7
carboxylic acids (e.g. C6H5COOH, CH3COCOOH, CH3COOH, C2H5COOH) and the
carboxylic or sulphonic acid resins.
7. A process according to claim 5 or 6, characterized in that said base is an
alkaline hydroxide or an alkaline carbonate or bicarbonate.
8. A process according to any one of claims 1 to 7, characterized in that each
R1 represents a methyl group.
9. A process for the preparation of a furanone of formula

comprising:
- the preparation of a compound (I), as defined in any one of claims 1 to 8, by a process
according to any one of claims 1 to 8; and
- the cyclisation of said compound (I).

The present invention relates to a process for the preparation of compounds of a 1,4-dialkyl-2,3-diol-1,4-butanedione
by a acidic aldol condensation between an alkyl glyoxal and an α-hydroxy ketone.

Documents:

http://ipindiaonline.gov.in/patentsearch/GrantedSearch/viewdoc.aspx?id=2s59Us9RQhc5e9tPfRmjyQ==&loc=wDBSZCsAt7zoiVrqcFJsRw==

« Previous Patent

Next Patent »

Patent Number

268734

Indian Patent Application Number

3801/KOLNP/2009

PG Journal Number

38/2015

Publication Date

18-Sep-2015

Grant Date

15-Sep-2015

Date of Filing

03-Nov-2009

Name of Patentee

FIRMENICH SA

Applicant Address

1, ROUTE DES JEUNES, P.O. BOX 239, CH-1211, GENEVA 8, SWITZERLAND

Inventors:

#	Inventor's Name	Inventor's Address
1	ANDREY, OLIVIER	CHEMIN DE PACOTY 7, CH-1297 FOUNEX SWITZERLAND

PCT International Classification Number

C07C45/72; C07C49/17; C07C45/00

PCT International Application Number

PCT/IB2008/051678

PCT International Filing date

2008-04-30

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	07108802.5	2007-05-24	EUROPEAN UNION