Organic compounds -- part of the class 532-570 series – Organic compounds – Sulfonic acids or salts thereof
Reexamination Certificate
2002-07-16
2003-10-28
Vollano, Jean F. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Sulfonic acids or salts thereof
C562S045000
Reexamination Certificate
active
06639103
ABSTRACT:
The present invention relates to 3-oxopropane-1-sulphonic acids and sulphonates, optionally in enantiomerically enriched form. The invention further relates to the use or enantiomerically enriched 3-oxopropane-1-sulphonic acids and sulphonates in the resolution or mixtures or enantiomers, for instance racemic mixtures. The invention relates in particular to (d)- and (l)-enantiomers of 3-oxopropane-1-sulphonic acids of general formula I or a salt thereof:
wherein R
1
and R
2
each independently represent a (cyclo)alkyl, an aryl, an aralkyl or an alkaryl group, wherein the groups optionally contain one or more heteroatoms, for instance O, S or N or wherein R
1
and R
2
together with the C-atoms to which they are attached and the intermediate C-atom form a 5-8 membered ring which may contain one or more, for instance 1-4, preferably 1-2 heteroatoms, with an ee >80%, preferably >90%, in particular >95%. The invention relates more in particular to 1,3-diphenyl-3-oxopropane-1-sulphonic acids of general formula I or a salt thereof, in particular the (d)- and (l)-enantiomers of these compounds, wherein R
1
and/or R
2
represent a phenylgroup, optionally substituted with one or more, in particular 1-5, groups R
3
, wherein the groups R
3
each independently represent H, halogen, hydroxy, a (cyclo)alkyl, aryl, alkaryl, aralkyl, (cyclo)alkoxy, aryloxy, amido, amino, nitro, acyl, carboxyl, aryloxycarbonyl, thiol or thioether group. Preferably R
1
and R
2
both represent an optionally substituted phenyl group.
It is known that sulphonic acids are strong acids and that such compounds could facilitate complex formation, in particular salt formation, in the resolution of mixtures of enantiomers (i.e. racemic mixtures or mixtures with a certain enantiomeric excess). A number of enantiomerically enriched sulphonic acids are known to be useful resolving agents, for instance camphor sulphonic acid (K. J. Brown, M. S. Berry, J. R. Murdoch, J. Org. Chem. 50, 4345, 1985; R. Dumont, A. Brossi, J. V. Silverton, J. Org. Chem. 51, 2515, 1986) and phenylethane sulphonic acid (R. Yoshioka, O. Ohtsuki, M. Senuma, T. Tosa, Chem. Pharm. Bull. 37, 883, 1989; E. J. Corey, K. A. Cimprich, Tetrahedron Lett. 33, 4099, 1992; R. Yoshioka, M. Tohyama, O. Ohtsuki, S. Yamada, I. Chibata, Bull. Chem. Soc. Jpn. 60, 649, 1987; R. Yoshioka, O. Ohtsuki, T. Da-Te, K. Okamura, M. Senuma, Bull. Chem. Soc. Jpn. 67, 3012, 1994). In Tetrahedron Lett. 33, 4099, 1992 Nobel prize winner Prof. E. J. Corey reports that chiral sulphonic acids are difficult to prepare. Chiral sulphonic acids would be very suitable in particular for the resolution of racemic mixtures of amines and amino acids (R. Yoshioka, O. Ohtsuki, T. Da-Te, K. Okamura, M. Senuma, Bull. Chem. Soc. Jpn. 67, 3012, 1994).
The present invention now provides resolving agents, which can be easily prepared and, therefore, are readily accessible.
Examples of 1,3-disubstituted-3-oxopropane-1-sulphonic acids and sulphonates (these derivatives are derived from the &agr;,&bgr;-unsaturated carbonyl compounds of the type 1,3-disubstituted-2-propene-1-one; the 1,3-diphenyl-2-propene-1-one derivatives are known as “chalcones”) or related compounds are known in the literature.
1,3-disubstituted-3-oxopropane-1-sulphonic acids and sulphonates and more particularly 1,3-diaryl-3-oxopropane-1-sulphonic acids and sulphonates, can be prepared by addition of sodium bisulphite to the C═C bond of the corresponding &agr;,&bgr;-unsaturated ketones (E. Knoevenagel, Ber. 31, 4038, 1904; K. H. Pfoertner, Helv. Chim. Acta 63, 664, 1980) according to the general reaction equations:
where MHSO
3
stands for, for instance, sodium or potassium bisulphite.
In the literature the applicant has found the following compounds:
3-(2-hydroxyphenyl)-1-(4-hydroxy-3-methoxyphenyl)-3-oxopropane-1-sulphonic acid (a),
1-(3,4-dimethoxyphenyl)-3-(4-hydroxy-3-methoxyphenyl)-3-oxopropane-1-sulphonic acid (b),
1-(3,4-dimethoxyphenyl)-3-(2-hydroxy-3-methoxy)-3-oxopropane-1-sulphonic acid (c),
barium 1-(3,4-dimethoxyphenyl)-3-(2-hydroxy-3-methoxy)-3-oxopropane-1-sulphonate (d),
1-phenyl-3-(2-hydroxyphenyl)-3-oxopropane-1-sulphonic acid (e),
sodium 1-phenyl-3-(2-hydroxyphenyl)-3-oxopropane-1-sulphonate (f),
1-phenyl-3-(2-hydroxy-3-methoxy-5-methylphenyl)-3-oxopropane-1-sulphonic acid (g),
sodium 1-phenyl-3-(2-hydroxy-3-methoxy-5-methylphenyl)-3-oxopropane-1-sulphonate (h)
1-phenyl-3-(4-hydroxy-3-methoxyphenyl)-3-oxopropane-1-sulphonic acid (i),
sodium 1-phenyl-3-(4-hydroxy-3-methoxyphenyl)-3-oxopropane-1-sulphonate (j),
sodium 1,3-diphenyl-3-oxopropane-1-sulphonate (k),
sodium 3-(p-chlorophenyl)-1-(2-pyridyl)-3-oxopropane-1-sulphonate (1),.
sodium 3-(p-chlorophenyl)-1-(3-pyridyl)-3-oxopropane-1-sulphonate (m).
sodium 3-(p-chlorophenyl)-1-(4-pyridyl)-3-oxopropane-1-sulphonate (n), and
sodium 3-(p-methoxyphenyl)-1-(4-pyridyl)-3-oxopropane-1-sulphonate (o).
Compounds (a) and (b) are described in O. Dahlman, K. Maanson, J. Wood Chem Technol. 16, 47, 1996 (“Analysis of low molecular weight lignin-derived sulphonates by capillary zone electrophoresis”). Compounds (c) and (d) are described in H. Richtzenhuin, B. Afredsson, Ber. 89, 378, 1956. Compounds (e) and (f) are described in H. Richtzenhuin, Ber. 72, 2152, 1939, and in K. Kratzl, H. Däubner, Monatsh. Chem. 78, 376, 1948. Compounds (g) and (h) are described in M. F. Browne, R. L. Shriner, J. Org. Chem. 22, 1320, 1957. Compounds (i) and (j) are described by K. Kratzl, H. Daubner, in Ber. 77, 519, 1944 and Ber. 79, 895, 1946. Compounds (k)-(o) are described in K. H. Pfoertner, Helv. Chim. Acta 63, 664, 1980 (“Substituted alkyl sulphonates by addition of sodium hydrogensulphite to chalcones”). Organic salts of such sulphonic acids are described by S. Rachwal, Zesz. Nauk. Uniw. Jagiellon, Pr. Chem. 32, 93, 1989 (“Addition of amine hydrosulphites to vinyl ketones. Conformation of the gamma-oxoalkanesulphonate anions”). However, in the above-mentioned literature sources only the chemical composition of the compounds is disclosed without any suggestion of chirality or enantiomerical enrichment.
The present invention therefore relates to a (d)- or (l)-enantiomer of a sulphonic acid of general formula I or a salt thereof wherein R
1
and R
2
are as defined above.
Suitable examples of R
1
and R
2
are, for instance, a C
1
-C
8
alkyl or a C
3
-C
12
cycloalkyl group, a 6-ring aryl group, a C
7
-C
12
alkaryl group, a C
7
-C
12
arylalkyl group, a C
4
or a C
5
heterocycloalkyl or C
4
or C
5
heteroaryl group, a C
5
-C
12
heterocycloalkyl or C
5
-C
12
heteroarylalkyl group or a C
5
-C
12
alkylheterocycloalkyl or C
5
-C
12
alkylheteroaryl group, in particular methyl, ethyl, n- and i-propyl, n-, s- and t-butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 1-naphthyl, o-, m- and p-methylphenyl, 2,4,6-trimethylphenyl, p-(t-butyl)phenyl, phenylmethyl, 2-phenylethyl, N-, O-and/or S-containing, unsaturated or saturated rings, in particular five or six rings for instance thienyl, furyl, pyranyl, pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, isothiazolyl, pyrrolidinyl, pyrrolinyl, isoxazolyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidyl and piperazinyl.
Preferably R
1
and/or R
2
represent a substituted or an unsubstituted aryl group. When R
1
and/or R
2
is a substituted aryl group, R
1
and/or R
2
has 1, 2, 3, 4 or 5 substituents R
3
, wherein preferably, the groups R
3
each independently represent halogen, hydroxy, a (cyclo)alkyl, aryl, alkaryl, aralkyl, (cyclo)alkoxy, aryloxy, amido, amino, nitro, acyl, carboxyl, aryloxycarbonyl, thiol or thioether group. R
1
and/or R
2
are preferably aryl groups mono-substituted at the para position. The group R
3
preferably represents a hydrogen atom, a halogen atom, for instance F, Cl, Br, I, a C
1
-C
6
alkoxy or cycloalkoxy group, a C
1
-C
6
alkyl or cycloalkyl group, a hydroxy group, an amino group of the formula —NR
4
R
5
where R
4
and R
5
independently of one another represent a hydrogen atom, a C
1
-C
6
alkyl or cycloalkyl grou
Nieuwenhuijzen Jose
Pouwer Kees
Vries Ton Rene
Wijnberg Hans
DSM N.V.
Vollano Jean F.
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