Organic compounds -- part of the class 532-570 series – Organic compounds – Cyclopentanohydrophenanthrene ring system containing
Reexamination Certificate
2000-08-30
2001-08-14
Badio, Barbara P. (Department: 1616)
Organic compounds -- part of the class 532-570 series
Organic compounds
Cyclopentanohydrophenanthrene ring system containing
C552S615000
Reexamination Certificate
active
06274746
ABSTRACT:
CROSS-REFERENCE TO RELATED APPLICATIONS
Not applicable
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
Not applicable
REFERENCE TO A MICROFICHE APPENDIX
Not applicable
FIELD OF THE INVENTION
This invention relates to a simple, and inexpensive way to allylically oxidize organic compounds having methylene groups activated by adjacent olefinic double bonds to &agr;,&bgr;-unsaturated carbonyl compounds, utilizing a metal hypochlorite and an alkyl hydroperoxide. The process provides a good example of green chemistry; the aqueous waste generated is non-toxic.
BACKGROUND OF THE INVENTION
Allylic oxidation of compounds bearing active methylene groups to corresponding &agr;,&bgr;-unsaturated carbonyl compounds is an important organic reaction having applications in a variety of fields ranging from agricultural products to pharmaceuticals and the like. Allylic oxidation reactions have traditionally been performed using a wide variety of chromium(VI) compounds. Among other common oxidants are potassium permanganate, manganese dioxide, ruthenium compounds, selenium dioxide, copper and its compounds. Catalytic oxidation using oxygen or air is known whereby metal compounds and N-hydroxy cyclic imides have been used as catalysts. Most of these procedures are not environmentally friendly, and typically suffer from one or more additional drawbacks such as unsatisfactory yields, use of large excess of the oxidant(s), harsh reaction conditions, use of toxic chemicals, difficulty in scaling up, generation of copious amount of toxic waste, use of expensive reagents etc. and therefore, are not industrially feasible processes for bulk production.
The use of tert-butyl hydroperoxide in combination with some of the oxidants such as chromium, ruthenium, and copper compounds has afforded allylically oxidized product(s) under relatively milder conditions but the reaction still utilizes the toxic metal compounds, and/or often requires use of toxic solvents such as benzene and the process produces toxic waste making the process eco unfriendly. Also, because of the incomplete and/or partial conversion, the product is often contaminated with the starting material and, quite often, complex mixture of products comprised of alcohols, ketones, hydroperoxides etc. is obtained.
Hence, a continuing need exists for a simple, efficient and cost effective as well as eco-friendly procedure for selectively effecting the allylic oxidation of organic compounds bearing an active methylene group, particularly &Dgr;
5
-steroids into corresponding &agr;,&bgr;-unsaturated ketones.
In our previous patent (Marwah et al, U.S. Pat. No. 5,869,709) we have described a new cost effective, simple procedure for allylic oxidation of a wide variety of organic compounds, utilizing sodium periodate or periodic acid and aqueous tert-butyl hydroperoxide. The procedure was developed successfully and is being utilized for the industrial production of one of our commercial products. However during commercial production it was observed that the only drawback associated with this process was production of large amount of aqueous waste containing salts of various lower oxidation stages of iodine such as iodates, iodides etc.
The present patent deals with a simple, eco-friendly, cost effective procedure based on green chemistry to the extent feasible, for the allylic oxidation of a wide variety of organic compounds having at least two allylic hydrogens into corresponding &agr;,&bgr;-unsaturated carbonyl compounds.
Sodium hypochlorite is a well-known oxidizing agent and a household bleaching agent and disinfectant and is easily and cheaply available under various brand names such as clorox. The commercially available aqueous solution of sodium hypochlorite comes with ~5.0-12.5% available oxidant (w/v, ~0.7 M-1.75 M). Concentration is expressed as % available chlorine since half the chlorine in bleach is present as sodium chloride. In the chemical synthesis, sodium and calcium hypochlorite have been successfully used to oxidize aldehydes into corresponding acids (—CHO into COOH) preferably in presence of a phase transfer catalyst, and secondary alcohols into ketones (—CHOH into —C═O) in presence of acetic acid, and primary alcohols to esters, ethers to esters, and thioethers to sulfoxides. Hypochlorites are effective, although infrequently utilized reagents for epoxidation of enones and polycyclic arenes. They are also reagents for N-chlorination, oxidative coupling, degradation reactions etc. and reactive methylene groups have occasionally been oxidized to the corresponding gem-diols. (Encyclopedia of reagents for organic synthesis; Editor-in-Chief: Leo A, Paquette, John Wiley & Sons 1995, p.966-68, 4580-86; Skarzewski J. and Siedlecka R., Organic Preparation and Procedures International, 24 (1992) 623-647 and Fieser's Reagent in Organic Synthesis, John Wiley & Sons, 1 1084 (1967); 4 456 (1974); 5 617 (1975); 6 543 (1977); 7 337 (1979); 8 461 (1980); 9 430 (1981); 10 365 (1982); 11 107 & 487 (1984); 15 293 (1990); 16 308 (1992); 17 316 (1994); 18 84 & 335 (1999); and 19 313 (1999)). It has also been reported that a methylene or methyl group attached to an aromatic ring can be oxidized to carboxylic acids provided the ring contains also an acetyl group. (Fieser's Reagent in Organic Synthesis 1, 1084) However, to the best of our knowledge, metal hypochlorites have never been used for a one step allylic oxidation of allylically activated methylene group to corresponding &agr;,&bgr;-unsaturated carbonyl compound (>CH
2
into >C═O).
BRIEF SUMMARY OF THE INVENTION
The present invention is concerned with a new green process for the allylic oxidation of organic compounds having at least two allylic hydrogen atoms on the same carbon atom. It is a simple, efficient, cost effective and eco friendly procedure, which generates non-toxic aqueous wastes in minimum possible amount. The present invention is the result of an extensive investigation to discover a process for allylic oxidation involving the use of so called green chemistry to the extent possible. The procedure involves reactively contacting a suitable organic compound with a combination of a metal hypochlorite and an alkyl hydroperoxide under conditions sufficient to effect oxidation of the allylic hydrogens on the organic compound to give corresponding &agr;,&bgr;-unsaturated carbonyl compound.
DETAILED DESCRIPTION OF THE INVENTION
The present process is extremely cost effective and useful both in terms of yield and operational simplicity. It is particularly good for the allylic oxidation of &Dgr;
5
-steroids and benzylic compounds. Good to excellent yields are obtained with low molar ratios of the reactants at sub ambient or near ambient reaction temperatures. A characteristic feature of the present invention is that it is an example of green chemistry to the extent feasible since it generates non-toxic aqueous waste materials in minimum possible amount.
The process of the present invention comprises allylically oxidizing an organic compound having at least two allylic hydrogen atoms on the same carbon atom into corresponding &agr;,&bgr;-unsaturated carbonyl compound.
The term “allylic oxidation” embraces, in the scope of the present invention, oxidation of an allylic compound by replacing two allylic hydrogens with oxygen, wherein the term “allylic compound” signifies in the scope of the present invention any organic compound incorporating the structure >C
a
═C
b
—C
c
H
n
within the molecule, wherein n is 2 or 3.
The term “benzylic compound” as defined in the scope of the present invention refers to an aromatic compound having a —CH
n
(n=2 or 3) group directly attached to an aromatic ring.
As utilized herein, including the claims, the term “reactants” collectively refers to allylic substrates, metal hypochlorite and alkyl hydroperoxide. Solvents, including both aqueous and organic solvents, are specifically excluded from the definition of reactants.
The term “inert organic solvent” as defined in the scope of the present invention refers to o
Lardy Henry A.
Marwah Ashok Kumar
Marwah Padma
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