Process for preparing monoacetylated hydroquinone compounds

Details Process for preparing monoacetylated hydroquinone compounds Process for preparing monoacetylated hydroquinone compounds

2000-10-03

2002-11-05

Killos, Paul J. (Department: 1625)

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

Organic compounds

Carboxylic acid esters

C568S319000, C568S322000, C568S323000

Reexamination Certificate

active

06476253

ABSTRACT:

The present invention relates to a process for preparing monoacetylated hydroquinone compounds and to the novel final products of the process.
Hydroquinone compounds are intermediates in demand for preparing natural substances, vitamins and carotenoids. For example 2,3,6-trimethylhydroquinone is used in the industrial total synthesis of &agr;-tocopherol (vitamin E) (Ullmann's Encyclopedia of Industrial Chemistry, 5
th
edition, Vol. A27, pp. 484 et seq., 4.11.2).
To prepare vitamin E compounds with olefinic isoprenoid side chains such as tocotrienol, another synthetic route is necessary because the acidic synthesis conditions usual for preparing tocopherol lead to isomerization or cyclization of the olefinic side chain (P. Karrer, H. Reutschler,
Helv. Chim. Acta
1944, 27, 20 1297; H. J. Kabbe, A. Widdig,
Angew. Chem. Int. Ed. Engl
. 1982, 21, 247-256, P. Schudel, H. Mayer, J. Metzger, R. Rüegg, O. Isler,
Helv. Chim. Acta
1963, 46, 2517).
Tocotrienols as well as tocopherols can be synthesized, for example, by reacting dihydroxyacetophenone compounds and E,E-farnesylacetone under basic conditions to give the corresponding 4-oxotocotrienols (H. J. Kabbe et al.,
Angew. Chem. Int. Ed. Engl
. 1982, 21, 247-256; B. C. Pearce et al.,
J. Med. Chem
. 1994, 37, 526) and subsequently reducing the 4-oxotocotrienols to the tocotrienols (H. J. Kabbe, H. Heitzer,
Synthesis
1978, 888; B. C. Pearce et al.,
J. Med. Chem
. 1994, 37, 526-541).
Monoacetylated hydroquinone compounds which can be converted into the corresponding dihydroxyacetophenone compounds by hydrolysis with, for example, methanolic sodium hydroxide (N. Cohen et al, J. Org. Chem 1978, 43 (19), 3723-3726) are therefore intermediates in particularly great demand.
It is known to prepare 2-acetyl-3,5,6-trimethylhydroquinone which is monoacetylated on the position 4 oxygen from 2,3,6-trimethylhydroquinone by reaction with BF
3
/acetic acid (N. Cohen et al, J. Org. Chem 1978, 43 (19), 3723-3726).
This process has the disadvantage that the precursors employed are themselves hydroquinones which have to be prepared from low-cost precursors such as phenols by an elaborate process with at least two synthesis steps (Ullmann's Encyclopedia of Industrial Chemistry, 5
th
edition, Vol. A27, p. 485, 4.11.3).
It is an object of the present invention to remedy the described deficiencies and to provide a novel process for preparing monoacetylated hydroquinone compounds with advantageous properties.
We have found that this object is achieved by a process for preparing monoacetylated hydroquinone compounds of the formula I
where
R
1
, R
2
or R
3
is, independently of one another, hydrogen or methyl, which comprises reacting diacetylphenol compounds of the formula
with peroxo compounds, where appropriate in the presence of an acid.
It was not to be expected that oxidation of asymmetrically acetylated phenols can be carried out with high selectivity in relation to an acetyl group in high yields.
Höfle et al. describe the monooxidation of a symmetrically diacylated dimethoxyphenol by means of a Baeyer-Villiger oxidation (Liebigs Ann. Chem. 1984, 1883-1904).
It is moreover known from another class of substances that re action of 3, 5-diacetyl-1,2,4-trimethoxybenzene with peracetic acid provides 5-acetoxy-3acetyl-1,2,4-trimethoxybenzene as byproduct in 30% yield (H.H. Lee et al., J. Chem. Soc. 1965, 2743-2749).
Peroxo compounds mean according to the invention inorganic or organic compounds comprising a peroxide group. Examples of preferred peroxo compounds are H
2
O
2
or peracids or salts thereof.
H
2
O
2
can be employed in the process according to the invention for example as aqueous solution.
Examples of preferred peracids are inorganic peracids or optionally substituted percarboxylic acids such as, for example, optionally substituted aryl peracids or optionally substituted C
1
-C
4
-alkyl peracids.
Examples of suitable substituents for the aforementioned percarboxylic acids are NO
2
or halogen.
Preference is given to optionally halogenated percarboxylic acids such as, for example, optionally halogenated aryl peracids or optionally halogenated C
1
-C
4
-alkyl peracids.
Halogenated percarboxylic acids mean percarboxylic acids which may be substituted by up to 6 identical or different halogen radicals such as, for example, F, Cl, Br or I, preferably F or Cl.
In a preferred embodiment of the process, the optionally substituted percarboxylic acids can be prepared in situ using H
2
O
2
and the corresponding optionally substituted carboxylic acid.
Examples of preferred optionally halogenated C
1
-C
4
-alkyl peracids are performic acid, peracetic acid, trif luoroperacetic acid or monopermaleic acid.
Examples of preferred optionally substituted aryl peracids are perbenzoic acid, m-chloroperbenzoic acid, 3,5-dinitroperbenzoic acid, p-nitroperbenzoic acid, monoperphthalic acid.
Suitable and preferred salts of the optionally substituted percarboxylic acids are their alkali metal or alkaline earth metal salts such as, for example, the magnesium salt of monoperphthalic acid.
Examples of preferred inorganic peracids or salts thereof are peroxosulfuric acids such as H
2
S
2
O
8
or H
2
SO
5
or alkali metal or alkaline earth metal salts thereof, such as, for example, K
2
S
2
O
8
, or peroxophosphoric acids such as H
4
P
2
O
8
or H
3
PO
5
or sodium perborates such as, for example, NaBO
3
.
Suitable and particularly preferred peroxo compounds in the process according to the invention are H
2
O
2
or m-chloroperbenzoic acid.
The diacetylphenol compounds of the formula II are reacted in the process according to the invention with peroxo compounds in the presence or absence of an acid.
The process according to the invention for preparing monoacetylated hydroquinone compounds of the formula I can in principle be carried out with peroxo compounds in the absence of an acid.
The process according to the invention for preparing monoacetylated hydroquinone compounds of the formula I can advantageously be carried out in a preferred embodiment in the absence of an acid specifically on use of peracids such as, for example, performic acid, peracetic acid, trifluoroperacetic acid, monopermaleic acid, perbenzoic acid, m-chloroperbenzoic acid, 3,5-dinitroperbenzoic acid, p-nitroperbenzoic acid, monoperphthalic acid, H
2
S
2
O
8
, H
2
SO
5
, H
4
P
2
O
8
or H
3
PO
5
as peroxo compounds.
The process can preferably and particularly advantageously be carried out when the diacetylphenol compounds of the formula II are reacted with peroxo compounds in the presence of an acid.
An acid means according to the invention a Brönsted or Lewis acid, a mixture of Brönsted acids, a mixture of Lewis acids or a mixture of Br6nsted and Lewis acids.
Preferred Brönsted acids are inorganic acids such as, for example, H
2
SO
4
or HCl or carboxylic acids, in particular optionally halogenated carboxylic acids, such as optionally halogenated C
1
-C
4
-alkylcarboxylic acids, such as, for example, formic acid, acetic acid, propionic acid or trifluoroacetic acid.
Preferred Lewis acids are the halides of main group three, such as, for example, BF
3
or AlCl
3
.
Preferred acids are formic acid and trifluoroacetic acid.
In a particularly preferred embodiment of the process, the following combinations of peroxo compounds and acids are used:
H
2
O
2
and formic acid,
H
2
O
2
and H
2
SO
4
,
H
2
O
2
and BF
3
,
m-chloroperbenzoic acid and trifluoroacetic acid,
K
2
S
2
O
8
and H
2
SO
4
,
NaBO
3
and trifluoroacetic acid or
NaBO
3
and trifluoroacetic acid/acetic acid.
The process according to the invention can advantageously be carried out with the addition of a buffer system such as, for example, an Na
2
HPO
4
buffer.
The process for preparing the compounds of the formula I can be carried out without additional solvent or in inert organic solvents such as, for example, CH
2
Cl
2
or CHCl
3
.
In the case where the process for preparing the compounds of the formula I is carried out without additional solvent, the acid may act as solvent. The acid is employed in excess in this case. The am

Affiliated with

Also associated with

Rating

Process for preparing monoacetylated hydroquinone compounds 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 preparing monoacetylated hydroquinone compounds, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for preparing monoacetylated hydroquinone compounds will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2966505