Process for preparation of polyhydric alcohols

Details Process for preparation of polyhydric alcohols Process for preparation of polyhydric alcohols

2002-03-05

2003-12-02

Wong, Edna (Department: 1753)

Chemistry: electrical and wave energy

Processes and products

Processes of treating materials by wave energy

Reexamination Certificate

active

06656328

ABSTRACT:

TECHNICAL FIELD
The present invention relates to a process for the preparation of polyhydric alcohol. Specifically, the invention relates to a process for the preparation of polyhydric alcohol by removing from a polyhydric alcohol compound having protected hydroxy groups the protecting groups of the hydroxy groups.
BACKGROUND ART
Compounds having hydroxy groups are highly reactive. Among such compounds, heterocyclic, aromatic, steroid and like compounds having hydroxy groups are useful as pharmaceutical intermediates, resin materials and the like.
When producing compounds such as heterocyclic compounds having hydroxy groups, aromatic compounds having hydroxy groups, steroid compounds having hydroxy groups and the like, the hydroxy groups thereof should be protected by protecting groups because they are extremely reactive.
Etherification is a typical method of protecting hydroxy groups. In this method, alkyl groups substitute for the hydrogen atoms of the hydroxy groups.
However, a method for removing the protecting groups (dealkylation method) without affecting the core chemical structure, easy to conduct and economical enough for industrial application has not yet been found.
Among the alkyl groups, methyl group has long been known to be a very stable protecting group for hydroxy group as described in “Protective Group in Organic Synthesis, Chapter 3, pp. 87-113, Theodora W. Greene (1981)”. Because of the very high stability of methyl group, demethylation must be conducted under severe conditions such as prolonged heating and the like while using expensive reagent, etc.
When demethylation is conducted under severe conditions, side reactions such as decomposition of the core chemical structure and the like occur. When the objective compound is a polyhydric alcohol compound having two or more hydroxy groups, demethylation does not completely progress and part of methylated hydroxy groups remains in the reaction system. This causes a reduced purity and a low yield of the objective compound.
Particularly, when the target compounds are steroid compounds having two or more hydroxy groups, heterocyclic compounds having two or more hydroxy groups or the like, the steroid or heterocyclic skeleton, etc. is unstable, and therefore specific reagents including aluminum halide, boron halide and the like are needed. However, these reagents are expensive and substantially impossible to recover. Furthermore, disposal of the waste liquid thereof is difficult, making these reagents unsuitable for industrial use.
Therefore, although the method of protecting hydroxy group with methyl group is advantageous in that the methyl group is stable as protecting group for hydroxy group, the application is narrowly limited.
Radiat. Phys. Chem., Vol.45, No.4, pp. 567-579 (1995) and AMERICAN LABORATORY, pp.37-40, JULY 1998, etc., disclose that demethylized compounds can be produced at a yield of about 80 to 96% by subjecting aromatic alcohols having hydroxy groups protected by methyl groups to demethylation by conducting microwave irradiation in acetic acid in the presence of 48% hydrogen bromide.
However, use of hydrogen bromide leads to the formation of byproducts which are difficult to remove, and this makes isolation and purification of the objective compounds very difficult. Therefore, the improvement in the purity of the desired compounds results in an extremely lowered yield. In addition, use of hydrogen bromide causes problems of environmental pollution, disposal of the waste after completion of the reaction and the like. Furthermore, this method requires after-treatment to be conducted by using an alkali; however, alkali treatment involves danger because it forms an unduly large amount of neutralization heat. Therefore, in practice, if crystals of the objective compounds are separated out by simply cooling the reaction mixture containing the objective compounds, the resultant crystals can be collected by filtering out and repeatedly washing the obtained crystals with water, or adding the crystals into a large volume of ice water. Employing these methods, when the objective compounds are water-soluble, makes the isolation of the objective compounds difficult. Therefore, the methods described above can be employed only when the objective compounds are compounds insoluble in water and separated out as crystals.
DISCLOSURE OF THE INVENTION
An object of the invention is to provide an industrially advantageous process for preparing polyhydric alcohols by readily removing protecting group(s) from hydroxy group(s) of polyhydric alcohol compounds wherein the hydroxy group(s) is protected.
Another object of the invention is to provide a process whereby the objected polyhydric alcohols are produced in a high yield and high purity.
A further object of the invention is to provide a process for preparing polyhydric alcohols wherein expensive and special reagents are not required and which is free from bothersome waste liquid treatment.
The inventors carried out intensive research to develop a novel process for preparing polyhydric alcohols and found that the above objects can be achieved by irradiating polyhydric alcohol compounds having protected hydroxy groups with microwaves in the presence of a basic compound or an acid having a pKa (acid dissociation exponent) of −8 to 3 at 25° C. The invention is accomplished by the above findings.
The invention provides a process for preparing polyhydric alcohol comprising the hydroxy protecting group(s) in the polyhydric alcohol compound is removed by irradiating polyhydric alcohol compound having protected hydroxy group(s) with microwaves in the presence of basic compound(s) or acid(s) having a pKa (acid dissociation exponent) of −8 to 3 at 25° C.
According to the invention, by irradiating polyhydric alcohol compound having protected hydroxy group(s) with microwaves in the presence of basic compound(s) or acid(s) having a specific acid dissociation exponent, the hydroxy protecting group(s) is removed, and thereby polyhydric alcohol compounds useful as pharmaceutical intermediates, pharmaceutical preparations and resin materials can be obtained in a short time, a high purity and a high yield without producing byproducts. Especially, when the objective polyhydric alcohol compounds are catechol, estradiol, morphine and the like, the process of the invention is advantageously employed because these compounds are used as medicines or raw materials for medicines and the purity thereof is important.
Polyhydric Alcohols
The polyhydric alcohols to be prepared by the process of the invention include heterocyclic compounds having 2 or more (preferably 2 to 6) hydroxy groups, alicyclic hydrocarbon compounds having 2 or more (preferably 2 to 6) hydroxy groups, monocyclic aromatic hydrocarbons having 2 or more (preferably 2 to 9) hydroxy groups and condensed polycyclic hydrocarbons having 2 or more (preferably 2 to 9) hydroxy groups.
Examples of heterocyclic compounds having 2 or more hydroxy groups are heterocyclic compounds having 2 to 6 hydroxy groups such as follows:
pyridines represented by the formula:
wherein n is 2 or 3,
pyrimidines represented by the formula:
wherein n is as defined above,
triazines represented by the formula:
wherein n is as defined above,
triazines represented by the formula:
wherein n is as defined above,
triazines represented by the formula:
wherein n is as defined above,
compounds represented by the formula:
wherein n is as defined above,
flavones represented by the formula:
wherein m
1
and m
2
are integers from 0 to 3, with the proviso m
1
+m
2
2, etc.
Specific examples of such heterocyclic compounds are 2,3-dihydroxypyridine, 2,4-dihydroxypyridine, 2,5-dihydroxypyridine, 2,6-dihydroxypyridine, 3,4-dihydroxypyridine, 3,5-dihydroxypyridine, 2,4,6-trihydroxypyridine, 2,4-dihydroxypyrimidine, 2,5-dihydroxypyrimidine, 3,4-dihydroxypyrimidine, 3,5-dihydroxypyrimidine, 2,4,5-trihydroxypyrimidine, 2,4,6-trihydroxypyrimidine, 4,5,6-trihydroxypyrimidine, 4,5,6-trihydroxytriazine, 3,5,6-trihydroxytriazine, 2,4,6-trihydroxytriazine, D-g

Affiliated with

Also associated with

Rating

Process for preparation of polyhydric alcohols does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Process for preparation of polyhydric alcohols, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for preparation of polyhydric alcohols will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3170074