Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acids and salts thereof
Reexamination Certificate
2003-04-16
2004-03-23
Killos, Paul J. (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acids and salts thereof
C585S639000
Reexamination Certificate
active
06710206
ABSTRACT:
INTRODUCTION
This invention pertains to poly(3-cyclopropyl-3-hydroxypropionate) compositions (I), a process for the preparation thereof and processes for the preparation of derivatives of (I). More specifically, this invention pertains to poly(3-cyclopropyl-3-hydroxypropionate) and its preparation by the reaction of cyclopropanecarboxaldehyde (CPCA) with ketene. The present invention also includes additional embodiments comprising the preparation of 3-cyclopropyl-3-hydroxypropionic acid (II) and salts (III) and esters (IV) thereof, 3-cyclopropylacrylic acid (V) and esters thereof (VI), and vinylcyclopropane (VII) from poly(3-cyclopropyl-3-hydroxypropionate) (I). Further embodiments of the present invention comprise a plurality of steps wherein (I) is first prepared and then converted to one or more of compounds (II), (III), (IV), (V), (VI) and (VII).
BACKGROUND OF THE INVENTION
Cyclopropylacetylene is a useful intermediate in the synthesis of reverse transcriptase inhibitors. Known processes for the synthesis of cyclopropylacetylene are limited, require the use of expensive starting materials and are difficult and expensive to practice. For example, J. M. Fortunak, Z. Wang and Y. Jin disclose in PCT Published Patent Application WO 99/06341 the condensation of cyclopropanecarboxaldehyde with malonic acid, halogenation of the formed 3-cyclopropylacrylic acid and dehydrohalogenation of the formed 1-halo-2-cyclopropylethylene to produce cyclopropylacetylene. Malonic acid is expensive and a significant weight portion of it is lost in the production of carbon dioxide byproduct. M. Nakazawa, T. Mitani, Y. Satake, S. Ohzono, G. Asanyma, and M. Shiono disclose in Published European Patent Application EP 847974 A1 a process for the halogenation of 3-cyclopropylacrylic acid followed by base treatment of the formed 2,3-dibromo-3-cyclopropylpropionic acid to produce cyclopropylacetylene. S. Slobodin,
Zh. Obshch. Khim.,
22, 1952,195,197, discloses the treatment of vinylcyclopropane with bromine and treatment of the formed (1,2-dibromoethyl)cyclopropane with potassium hydroxide in 2-ethoxyethanol to inherently produce the unisolated intermediates 1-bromo-1-cyclopropylethylene and 1-bromo-2-cyclopropylethylene which are converted under the basic reaction conditions to cyclopropylacetylene. Vinylcyclopropane is difficult to prepare and is not commercially available in bulk.
In view of the above-described state of the art, it would be very desirable to produce vinylcyclopropane and 3-cyclopropylacrylic acid using inexpensive and readily available starting materials.
BRIEF SUMMARY OF THE INVENTION
The first embodiment of the present invention concerns novel poly(3-cyclopropyl-3-hydroxypropionate) compositions (I) and the preparation thereof, i.e., compositions (I) having the general formula:
wherein n is an integer greater than 1, e.g., 2 to 2000, preferably 10 to 500, and most preferably, about 10 to 100. Compositions (I) may be prepared by contacting cyclopropanecarboxaldehyde (CPCA) and ketene in the presence of a catalyst.
Further embodiments of our invention include:
(a) The preparation of 3-cyclopropyl-3-hydroxypropionic acid (II) by contacting (I) with water.
(b) The preparation of metal 3-cyclopropyl-3-hydroxypropionate salts (III) by contacting (I) with an aqueous metal base.
(c) The preparation of alkyl 3-cyclopropyl-3-hydroxypropionate esters (IV) and the oxidation products thereof by contacting (I) with an alkanol.
(d) The preparation of 3-cyclopropylacrylic acid (V) by heating (I).
(e) The preparation of alkyl 3-cyclopropylacrylate esters (VI).
(f) The preparation of vinylcyclopropane (VII) by heating (I).
(g) The preparation of a mixture of 3-cyclopropylacrylic acid (V) and vinylcyclopropane (VII) by heating (I).
(h) The preparation of vinylcyclopropane (VII) by heating 3-cyclopropyl-acrylic acid (V)
(i) The preparation of vinylcyclopropane (VII) by heating 3-cyclopropyl-3-hydroxypropionic acid (II)
(j) 3-Cyclopropyl-3-acyloxypropionic acids wherein the acyloxy group is the residue of a C
2
-C
14
carboxylic acid (VIII).
(k) The preparation of vinylcyclopropane (VII) by the steps comprising: (1) contacting 3-cyclopropyl-3-hydroxypropionic acid (II) with a carboxylic acid anhydride to provide an anhydride of a 3-cyclopropyl-3-acyloxypropionic acid (VIII); (2) contacting the anhydride from step (1) with water to form a 3-cyclopropyl-3-acyloxypropionic acid (VIII); and (3) contacting the 3-cyclopropyl-3-acyloxypropionic acid from step (2) with heat, an acid or a base to convert acid (VIII) to vinylcyclopropane (VII).
(l) A mixed carboxylic anhydride comprising a 3-cyclopropyl-3-acyloxypropionyl residue and the acyl residue of a carboxylic acid.
(m) The preparation of 3-cyclopropyl-3-hydroxypropionic acid (II) by contacting 3-cyclopropylacrylic acid (V) with water.
(n) 3-Cyclopropyl-beta-propiolactone.
(o) The preparation of vinylcyclopropane by heating 3-cyclopropyl-betapropiolactone.
Further embodiments of the invention include the combination of the step of preparing composition (I) with any of processes (b), (d), and (f)-(i). The compositions which may be obtained in accordance with the present invention may be converted ultimately to cyclopropylacetylene according to known procedures such as those discussed hereinabove.
DETAILED DESCRIPTION OF THE INVENTION
As mentioned above, the first embodiment of the present invention concerns novel poly(3-cyclopropyl-3-hydroxypropionate) compositions (I) and the preparation thereof. The novel compositions (I) have the general formula:
wherein n is an integer greater than 1, e.g., 2 to 2000, preferably 10 to 500, and most preferably, about 10 to 100. Because of their lower viscosity and ease of handling, compositions (I) having lower molecular weights, e.g., wherein n is an integer of 10 to 500 are preferred. The most preferred compositions (I) are those wherein n is an integer of 10 to 100. As used herein n when multiplied by the molecular weight of the repeat unit in the polymer defines the number average molecular weight for the polymer.
The novel poly(3-cyclopropyl-3-hydroxypropionates) may be prepared by the reaction of ketene and CPCA in the presence of a catalyst and, optionally, in the presence of solvent. Catalysts for the reaction include Lewis acids, e.g., salts such as halides, carboxylates and alkoxides of various metals such as alkali metals, alkaline earth metals, and transition metals, e.g., lithium, sodium, potassium, rubidium, cesium, beryllium, magnesium, calcium, strontium, barium, manganese, osmium, titanium, aluminum, zinc, cadmium, mercury, copper, silver, gold, nickel, palladium, platinum, cobalt, rhodium, iridium, iron, ruthenium, chromium, molybdenum, tungsten, vanadium, niobium, tantalum, zirconium and hafnium, tin, lead and antimony; boron trifluoride; and tertiary amines such as trialkylamines, e.g., trialkylamines containing a total of up to about 30 carbon atoms, pyridine, N-alkylmorpholine and the like. The anion of the salts may be a halide, e.g., chloride or bromide; a carboxylate selected from the residues of saturated and unsaturated, branched or linear aliphatic, mono- and poly-carboxylic acids; and alkoxides containing up to about 12 carbon atoms. Zinc, iron and magnesium salts of aliphatic, mono-carboxylic acids containing 2 to 20 carbon atoms represent the preferred metal carboxylate catalysts. Specific examples of such compounds include iron acetate, magnesium acetate, zinc acetate and zinc 2-ethylhexanoate. These catalysts may be employed in concentrations of up to 10 weight percent, based on the weight of the metal or amine component of the catalyst and the weight of the final polymer (I) product. Normally, the catalyst will be used in concentrations of about 100 to 10,000 parts per million by weight (ppmw), preferably about 200 to 3000 ppmw (same basis).
Although the process for the preparation of the poly(3-cyclopropyl-3-hydroxypropionates) may be carried out over a broad temperature range, e.g., −20 to 250° C., the use of temperatures in the range of about 0 to 100° C. are more typical.
Barnette Theresa Sims
Boaz Neil Warren
Hubbs John Clark
Blake MIchael J.
Eastman Chemical Company
Killos Paul J.
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