Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2001-12-21
2003-03-11
Owens, Amelia (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C549S272000, C549S273000, C549S295000
Reexamination Certificate
active
06531616
ABSTRACT:
FIELD OF THE INVENTION
This invention is in the field of synthetic organic chemistry. This invention pertains to a method to produce &agr;-methylenelactones and &agr;-substituted hydrocarbylidene lactones. More specifically, this invention pertains to a simple, efficient and economic method to produce &agr;-methylene-&ggr;-butyrolactone from &ggr;-butyrolactone.
TECHNICAL BACKGROUND OF THE INVENTION
&agr;-Methylenelactones have been the subject of intensive synthetic studies. Specifically, the &agr;-methylene-&ggr;-butyrolactone group is an important structural feature of many sesquiterpenes of biological importance. In addition, &agr;-methylene-&ggr;-butyrolactones are regarded as potential key monomers in both homopolymers and copolymers. One main use for &agr;-methylene-&ggr;-butyrolactone is as an intermediate for the production of 3-methyltetrahydrofuran. Currently the cost of &agr;-methylene-&ggr;-butyrolactone is too high to warrant commercial production of the resulting polymers. Some of the current synthetic routes suffer from low yields, byproduct formation and expensive starting materials.
An early synthesis of &agr;-methylene-&ggr;-butyrolactone involves two steps (Martin et al.,
J. Chem. Soc
. D 1:27 (1970)). The first is carboxylation of &ggr;-butyrolactone with methyl methoxymagnesium carbonate (Stiles' reagent) to produce the acid. Next, the acid is briefly treated with a mixture of aqueous formaldehyde and diethylamine, followed by a separate treatment of the crude product with sodium acetate in acetic acid. The first step requires 6-7 hours and affords almost quantitative yields, whereas the second step can be accomplished in less than 30 minutes but with yields of only 50%.
Murray et al. (
Synthesis
1:35-38 (1985); see also U.S. Pat. No. 5,166,357) disclose a route to &agr;-methylene-&ggr;-butyrolactone that also involves a two-step sequence consisting of the reaction of &ggr;-butyrolactone with ethyl formate in the presence of base, followed by refluxing the resulting &agr;-formyl-&ggr;-butyrolactone sodium salt under nitrogen with paraformaldehyde in tetrahydrofuran. Distillation affords the desired &agr;-methylene-&ggr;-butyrolactone as a colorless oil. This reaction sequence can best be explained by formyl transfer from carbon to oxygen followed by elimination of carboxylate anion.
Essentially all approaches to &agr;-methylene-&ggr;-butyrolactone are liquid-phase processes. One exception is the vapor-phase process described in JP 10120672, which involves subjecting &ggr;-butyrolactone or an alkyl-substituted &ggr;-butyrolactone, in which one or more hydrogen atoms at the &bgr;- or &ggr;-position of the &ggr;-butyrolactone are substituted with C
1
-C
18
alkyl groups, to a gaseous phase catalytic reaction using a raw material gas containing formaldehyde or its derivative in the presence of a catalyst. Molecular oxygen is preferably added to the raw material gas and the catalyst is preferably silica alumina catalyst. Specifically, a gaseous mixture of &ggr;-butyrolactone, formaldehyde, water, nitrogen and oxygen are passed through a reactor packed with Wakogel C-200, pretreated with an aqueous potassium hydroxide solution and heated at 330° C., to afford &agr;-methylene-&ggr;-butyrolactone at a conversion of 35.5% and a selectivity of 46.9%.
The synthetic approaches to date typically involve two-step processes that use highly flammable solvents such as tetrahydrofuran (THF) or diethyl ether. Impurities are often present at high concentrations and the final distillation leaves significant amounts of residual polymer. In McMurry's synthesis of &agr;-methylene-&ggr;-butyrolactone (
J. Org. Chem
. 42:1180-5 (1977)), a solution of &ggr;-butyrolactone and diethyl oxalate is added to a cooled solution of sodium ethoxide in ethanol. The &agr;-oxalyl sodium salt is formed in solution. The solvent is removed in vacuo and the residual pasty material is taken up in water and diethyl ether and then acidified to give the &agr;-ethyl oxalyl &ggr;-butyrolactone (vide infra). This compound is then dissolved in THF and added to a cooled suspension of lithium hydride in THF. Formaldehyde gas is bubbled in to produce &agr;-methylene-&ggr;-butyrolactone. The final overall yield is reported to be 83%. While this process affords &agr;-methylene-&ggr;-butyrolactone in fairly high yield and purity, it is not readily adapted to large scale reactions required for polymer production.
Although the above methods for the production of &agr;-methylene-&ggr;-butyrolactone and &agr;-substituted hydrocarbylidene lactones are useful, they are time consuming and do not obtain high product purity. In addition, the known methods are not readily adaptable to large scale reactions. Another problem is to find a more effective and economical method of production than are currently available. The present method offers a user-friendly process resulting in high yields and good selectivity. Furthermore, the process eliminates high levels of the residual &ggr;-butyrolactone starting material which has been shown to limit the scope of polymerization methods used in the production of &agr;-methylene-&ggr;-butyrolactone. The critical advance is the isolation of the intermediate compound which is crucial in obtaining high purity of the &agr;-methylene-&ggr;-butyrolactone and &agr;-substituted hydrocarbylidene lactone product as a result of the method presented herein.
SUMMARY OF THE INVENTION
The instant invention relates to a process for preparing &agr;-methylenelactones of Formula III comprising the steps:
(a) contacting lactones of Formula I with an oxalate in the presence of a base and a solvent to form an intermediate mixture comprising the compound of Formula II and isolating the compound of Formula II from the intermediate mixture
(b) treating the isolated compound of Formula II with formaldehyde to form a product mixture; and
(c) optionally isolating the &agr;-methylenelactones of Formula III from the product mixture.
wherein,
n=1-11;
R is hydrocarbyl or substituted hydrocarbyl;
X is a cation; and
R
1
, R
2
, R
3
and R
4
, taken independently are hydrogen, hydrocarbyl or substituted hydrocarbyl, C
1
-C
18
unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted cycloalkyl containing at least one heteroatom, unsubstituted or substituted aromatic ring, and unsubstituted or substituted aromatic ring containing at least one heteroatom.
The invention further provides a process for the preparation of compounds of Formula III wherein any two of R
1
, R
2
, R
3
and R
4
are members of a ring structure selected from the group consisting of, unsubstituted or substituted cycloalkyl, unsubstituted or substituted cycloalkyl containing at least one heteroatom in the ring, unsubstituted or substituted aromatic ring, and unsubstituted or substituted aromatic ring containing at least one heteroatom in the ring.
Another embodiment of the invention is a process for preparing &agr;-substituted hydrocarbylidene lactones of Formula IV comprising the steps:
(a) contacting lactones of Formula I with an oxalate in the presence of a base and a solvent to form an intermediate mixture comprising the compound of Formula II and isolating the compound of Formula II from the intermediate mixture;
(b) treating the isolated compound of Formula II with a formaldehyde derivative to form a product mixture; and
(c) optionally isolating the &agr;-substituted hydrocarbylidene lactones of Formula IV from the product mixture.
wherein,
n=1-11;
R is hydrocarbyl or substituted hydrocarbyl;
X is a cation; and
R is hydrocarbyl or substituted hydrocarbyl; and
R
1
, R
2
, R
3
and R
4
taken independently are hydrogen, hydrocarbyl or substituted hydrocarbyl, C
1
-C
18
unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted cycloalkyl containing at least one heteroatom, unsubstituted or substituted aromatic ring, and unsubstituted o
Brandenburg Charles
Puts Rutger D.
Tarburton Kenneth R.
Belopolsky Inna Y.
E. I. du Pont de Nemours and Company
Owens Amelia
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