Single step process for the preparation of poly...

Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – From organic oxygen-containing reactant

Reexamination Certificate

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C562S401000, C562S407000, C562S418000, C562S509000, C562S512000, C562S538000, C562S590000, C562S859000, C524S714000, C524S725000, C524S765000, C524S770000, C524S878000

Reexamination Certificate

active

06239252

ABSTRACT:

FIELD
This invention relates to a single step process for the preparation of poly (oxyalkylene)-alpha, omega-dicarboxylic acids having formula HO
2
CCH
2
O(CH
2
CHRO)
n
CH
2
CO
2
H, wherein R is hydrogen, methyl or mixtures of hydrogen and methyl on the individual molecule and n is an integer from 100 to about 2500. More particularly, the invention relates to a process for the preparation of poly (oxyalkylene)-alpha, omega-dicarboxylic acids by oxidation of corresponding poly (oxyalkylene glycol)s in the presence of an oxidizing agent.
BACKGROUND
Poly (oxyalkylene)-alpha, omega-dicarboxylic acids are finding ever increasing applications in various branches of chemistry. Some of the applications are as follows:
1. Water soluble support for Merrifield type peptide synthesis (R. P. Garfield and G. M. Ananthramaiah, J. Am. Chem. Soc. 101, 3394 (1979), G. P. Royer, Methods Enzymol. 136, 302 (1987)).
2. Polymeric drug carriers—prodrugs (K. Ulbrich and J. Kopecek, Macromol. Chem. 187, 1131 (1986), T. Ouchi, Y. Hogihara, K. Takashashi, Y. Takano and I. Igarashi, Drug Design and Discovery, 9, 93 (1992), R. B. Greenwald, C. W. Gilbert, A. Pendri, C. D. Conover, J. Xia and A. Maertinez, J. Med. Chem. 39, 424 (1996), S. Zalipski, C. Gilon and A. Zilkha, Eur. Polym. J. 19, 1177 (1983), M. Pecher, J. Strochalm and K. Ulbrich, Makromol. Chem. Phys. 198, 1009 (1997)).
3. Antistatic agents in polyamide/s (I. Jan and C. Frantisek, Czech. CS. 234,832).
4. Conjugates with enzyme-metal ion for improved stability and activity of enzymes (Y. Tukayuki, M. Takeshi, T. Katsunobu, S. Yuji, T. Yukata and I. Yuji, Biochem. Biophys. Res. Commun. 145, 908 (1987), N. Veyarma, M. Nakata and A. Nakamura, Polym. J. (Tokkyo) 17, 721 (1985), T. Katsunobu, O. Kimiko, Y. Takayuki, S. Yuji, K. Yoh, M. Ayako and I. Yuji, J. Biotechnol 8, 135 (1988)).
5. Conjugates with hemoglobin for oxygen carrying blood substitute (A. Yabuki, K. Yamaji, H. Ohki and Y. Iwashita, Transfusion (Philadelphia) 30,516 (1990).
6. Conjugates with lipids for improved longevity in blood circulation (3. Gabriel and C. Greger, Biochem. Biophys. Acta. 1146, 157 (1993).
7. Surface modyfying agents for transition metal alluminides (D. M. Zehner, Surf. Rev. Lett. 3, 1637 (1996).
8. Stabilizer for water based epoxy formulations (H. E. Friend and C. J. Stark, PCT Intl. Appl. WO 9619, 514) and so on.
In order to meet these growing requirements for poly (oxyalkylene)-alpha, omega-dicarboxylic acids, various methods for their preparation have been developed so far which can broadly be classified into following two types.
1. Carboxymethylation of poly (oxyalkylene glycol)s.
In this method of preparation, terminal hydroxymethyl groups of poly (oxyalkylene glycol)s are derivatized with carboxymethyl groups (—CH
2
—COOH groups) so as to obtain poly (oxyalkylene)-alpha, omega-dicarboxylic acids. This method essentially involves following steps: A) Activation of terminal hydroxyl groups by reacting poly (oxyalkylene glycol)s with strong bases such as potassium tertiary butoxide, silver oxide, sodium hydroxide etc. B) Reaction of alcoholate so obtained with reagents like bromo ethyl acetate, chloroethyl acetate etc. C) Saponification of ethyl ester followed by acidification of reaction mixture. D) Isolation of product.
PRIOR ART REFERENCES
The above method has been used by various researchers (R. P. Garfield and G. M. Anantharamaiah, J. Am. Chem. Soc. 101, 3394 (1979), K. Ulbrich, J. Strohalm and J. Kopecek, Makromol. Chem. 187, 1131 (1986), M. Pecher, J. Strohalm and K. Ulbrich, Makromol, Chem. Phys. 198, 1009 (1997), A. F. Buckmann, M. Morr and J. Goete, Makromol. Chem 183, 1379 (1981), I. Keji, I. Yuji and O. Taketashi, Eur. Pat. Appl. EP. 206, 448, A. J. Martinez and R. B. Greenwald, U.S. U.S. Pat. No. 5,605,976A). Since this method of preparation for poly (oxyalkylene)-alpha, omega-dicarboxylic acids is a multistep process involving speciality reagents, it is not attractive for large scale production.
2. Oxidation of Poly (oxyalkylene glycol)s.
A number of patents which are based on this technique have been filed. Japanese patent, Japan Kokai 7300,528 discloses the preparation of low molecular weight poly (oxyethylene)-alpha,omega-dicarboxylic acids by oxidation of poly (ethylene glycol)s using oxygen and concentrated nitric acid as oxidizing agent in an autoclave at 80° C. under 3 Kg/cm
2
pressure (E. Yonemitsue, T. Icshiki, Y. Kijima and T. Matsumoto, Japan Kokai 7300,528). Low molecular weight poly (ethylene glycol)s have also been oxidized using Platinum/charcoal catalysts and oxygen under pressure at 50° C. in a column reactor (Sanyo Chemical Industries Ltd. Jpn. Kokai Tokyo Koho JP 8258,642). Preparation of poly (oxyethylene)-alpha, omega-dicarboxylic acids by oxidation of poly (ethylene glycol)s in presence of cobalt acetate quadrahydrate, using oxygen under pressure at 140° C. and using a mixture of catalysts viz. Copper acetate, ammonium venadate, nitric acid and formaldehyde at 50 to 90° C. has also been reported (Nikka Chemical Industry Co. Ltd. Jpn. Kokai Tokyo Koho JP 5901,443 and W. Disteldorf, W. Eisfeld and H. Hellbach, Gen. Offen. DE. 3,209, 434, respectively).
Czechoslovakian patent CS. 234,832 discloses the preparation of poly (oxyethylene)-alpha, omega-dicarboxylic acids of molecular weights in the range of 1000 to 3000 by oxidation of corresponding poly (ethylene glycol)s using potassium dichromate and sulfuric acid at 70° C. (I. Jan and C. Frantisek, Czech. Cs. 234, 832). Microbial oxidation of poly (ethylene glycol)s of molecular weights from 200 to 2000 by Rhinocladiella actrovirens has been reported, wherein, the time period required for oxidation was up to 14 days (M. Shuichi, Y. Nobuo and Y.Sadao, Makromol. Chem. Rapid. Commun. 10, 63 (1989)). Recently, U.S. Pat. No. 5,256,819 has disclosed preparation of poly (oxyalkylene)-alpha, omega-dicarboxylic acids of wide range of molecular weights by oxidation of corresponding poly (oxyalkylene glycol)s using oxygen, nitric acid and 2,2,6,6 tetramethylpiperidine-1-oxyl as oxidizing agent (H. E. Fried U.S. Pat. No. 5,256,819).
Most of the above cited oxidation processes require either harsh reaction conditions such as high temperature, pressure etc. or special reagents like stable free radicals-2,2,6,6 tetramethylpiperidine-1-oxyl. Also, in most cases conventional work up procedures which involve neutralization of oxidizing agents, concentration of solvents, removal of oxidation by-products and isolation of products, are followed. Thus, there is a need to develop and simpler method for oxidation of poly (oxyalkylene glycol)s having wide range of molecular weights to corresponding dicarboxylic acids.
OBJECTS
It is therefore an object of the present invention to provide a single step process for the preparation of poly (oxyalkylene)-alpha, omega-dicarboxylic acids of low to very high molecular weights in high yields by oxidation of corresponding glycols using commonly available oxidizing agents under mild reaction conditions such as room temperature, atmospheric pressure etc.
Another object is to provide a simpler method for removing the oxidation by-products from reaction mixture and thus obviate the drawbacks in conventional work up procedures.
As compared to various oxidizing agents used in the prior art processes, Jone's reagent, which is a mixture of chromium trioxide and sulfuric acid and water is, a strong oxidizing agent which oxidizes hydroxymethyl groups to carboxyl groups at temperatures in the range of 10° C. to room temperature (25° C.) (L. S. Loeffler, S. F. Britcher and W. Bauumgarten, J. Med. Chem. 13, 926 (1970). Despite such strong oxidizing power, Jone's reagent has not been used in oxidation of poly (oxyalkylene glycol)s to corresponding dicarboxylic acids.
SUMMARY
This invention uses Jone's reagent to achieve the objects of the present invention. It has now been found that poly (oxyalkylene)-alpha, omega-dicarboxylic acids can be produced in high yields by oxidation of poly (oxyalkylene glycol)s using Jone's reagent as oxidizing agent in suitable

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