Method for reduction of substituted malonates to diols

Details Method for reduction of substituted malonates to diols Method for reduction of substituted malonates to diols

2002-04-25

2003-03-25

Davis, Brian (Department: 1621)

Organic compounds -- part of the class 532-570 series

Organic compounds

Oxygen containing

C568S853000, C568S864000

Reexamination Certificate

active

06538163

ABSTRACT:

BACKGROUND
This invention relates generally to a method for reducing substituted malonates to diols using sodium aluminum hydride.
Substituted malonates have been reduced to the corresponding diols with lithium aluminum hydride or with lithium borohydride, as described in U.S. Pat. No. 4,982,016. However, reduction of substituted malonates with sodium aluminum hydride has not been reported.
Sodium aluminum hydride typically is available commercially as a slurry in toluene at a lower cost than lithium aluminum hydride or lithium borohydride. A method for reducing substituted malonates to diols, without using lithium aluminum hydride or lithium borohydride would be more economical and would be commercially valuable.
STATEMENT OF INVENTION
The present invention is directed to a method for reducing a malonate of formula R
1
R
2
C(CO
2
R
3
)(CO
2
R
4
) to a diol of formula R
1
R
2
C(CH
2
OH)
2
comprising treating said malonate with sodium aluminum hydride; wherein R
1
is aryl, alkyl, aralkyl, alkenyl, or alkynyl; R
2
is hydrogen, aryl, alkyl, alkenyl, or alkynyl; and R
3
and R
4
are independently alkyl or aralkyl.
DETAILED DESCRIPTION
Unless otherwise specified, all percentages herein are stated as weight percentages, temperatures are in ° C., and volumes in mL.
An “alkyl” group is a saturated hydrocarbyl group having from one to twenty carbon atoms in a linear, branched or cyclic arrangement. Preferably, alkyl groups have from one to twelve carbon atoms, and most preferably, from one to six carbon atoms. An “alkenyl” group is an “alkyl” group in which at least one carbon-carbon single bond has been replaced with a double bond. An “alkynyl” group is an “alkyl” group in which at least one carbon-carbon single bond has been replaced with a triple bond. Preferably, alkyl, alkenyl and alkynyl groups are acyclic and unsubstituted. Alkyl, alkenyl and alkynyl groups optionally are substituted with one or more hydroxy, halo, alkyl, alkenyl, alkoxy, amino or alkylamino groups, with substitution by one or more halo groups being possible on alkyl or alkoxy groups. An “aryl” group is a substituent derived from an aromatic compound, including heterocyclic aromatic compounds having at least one nitrogen, oxygen or sulfur atom in the ring. An aryl group has a total of from five to twenty ring atoms, and has one or more rings which are separate or fused. Preferably, aryl groups have from five to ten ring atoms. Substitution on aryl groups of one or more hydroxy, halo, alkoxy, alkyl, alkenyl or alkynyl groups is permitted, with substitution by one or more halo groups being possible on alkyl, alkenyl or alkoxy groups. An “aralkyl” group is an “alkyl” group substituted by an “aryl” group.
In one embodiment of the invention, R
1
is aryl and R
2
is hydrogen. Preferably, R
1
is phenyl and R
3
and R
4
are alkyl, i.e., the substituted malonate is a dialkyl phenylmalonate. R
3
and R
4
represent the same alkyl group or different alkyl groups. The 2-phenyl-1,3-propanediol product obtained in this embodiment is useful as an intermediate for the corresponding diol dicarbamate compound, an important intermediate in the dye industry and in pharmaceutical applications. In another embodiment of the invention, R
1
and R
2
are alkyl, wherein R
1
and R
2
are the same or different alkyl groups. Preferably, R
1
and R
2
are n-butyl and R
3
and R
4
are alkyl, wherein R
3
and R
4
are the same or different alkyl groups.
Typically, the method of this invention is performed in an ethereal solvent in which sodium aluminum hydride is soluble, for example, tetrahydrofuran (“THF”) or glymes. Suitable glymes include, for example, monoglyme (dimethoxyethane), diglyme (2-methoxyethyl ether), triglyme (triethylene glycol dimethyl ether), and tetraglyme (tetraethylene glycol dimethyl ether). The preferred solvent is THF. The preferred temperature range for the reduction is from −90° C. to 150° C., more preferably from 25° C. to 90° C., and most preferably from 40° C. to 75° C. The reduction reaction is continued until the substituted malonate starting material has been substantially consumed. The preferred reaction time is from 0.1 hours to 48 hours, more preferably from 6 hours to 40 hours, and most preferably from 8 hours to 30 hours. Preferably, the amount of SAH, relative to the amount of malonate, is from 1 to 10 equivalents, more preferably from 1 to 5 equivalents, and most preferably from 1 to 2 equivalents. In one embodiment of the invention, sodium aluminum hydride (“SAH”) is introduced in the form of a slurry comprising SAH and toluene. Preferably, the slurry has from 1% to 75% SAH and from 25% to 99% toluene, more preferably from 10% to 60% SAH and from 40to 90% toluene, and most preferably from 30% to 50% SAH and from 50% to 70% toluene.


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