# US 2008/0188680 A1 · Process Improvement Using Solubility Characteristics

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- Number: US 2008/0188680 A1
- Document ID: US20080188680A1
- Status: Published application
- Kind: A1
- Application number: 11/817,263
- Filed: 2006-02-21
- Published: 2008-08-07
- Earliest claimed: 2005-02-28
- Inventors: Michael J. Gentilcore
- Web page: https://patentgrep.com/patent/US20080188680A1

## CPC

- C07C 201/12: by reactions not involving the formation of nitro groups
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

The present invention is directed to a process of maximizing the solubility of a nonelectrolyte solute in a solvent by operating within an optimal temperature range at conditions wherein the nonelectrolyte solute is not a pure liquid. In particular, the process of the present invention is directed to conversion of a carboxylic acid compound to an ester under conditions wherein the solubility of the ester in an alcoholic solvent approaches ideal solubility behavior.

## Claims

### Claim at position 1

1-43. (canceled)

### Claim 44

A process having an operating temperature range, Tmin to Tmax, at which solubility of a non-electrolyte solute in a solvent is maximized, the process comprising:
forming a mixture comprising the non-electrolyte solute and the solvent, wherein the solubility of the solute in the solvent is less than the ideal solubility at temperature, T, the temperature of the mixture being between Tmin and Tmax; wherein
γsolute is the activity coefficient of the solute in a two component mixture of the solute in the solvent at a temperature, T, derived from equation (5);
ln


γ
solute

x
solute
=
-
Δ


H
solute
F
R

(
1
T
-
1
T
m

(
solute
)
)
(
5
)
γsolute is the mole fraction of dissolved solute in a saturated two component mixture of solute and solvent at a temperature, T, in K;
R is the ideal gas constant in cal/K·mol;
−ΔHFsolute is the heat of fusion in cal/g·mol of the solute;
Tm(solute) is the absolute melting temperature of the solute, in K;
Tmin is a temperature, in K, where an absolute value of γsolute is greater than one and less than about 10 and the second derivative of a function of γsolute with respect to temperature becomes a positive value; and
Tmax is a temperature, in K, which is greater than Tmin and less than (Tmin+0.8(Tm(solute)−Tmin)).

### Claim 45

A process having an operating temperature range, Tmin to Tmax, at which solubility of a non-electrolyte solute in a solvent is maximized, the process comprising forming a mixture comprising the non-electrolyte solute and the solvent, wherein the solubility of the solute in the solvent is less than the ideal solubility at a temperature, T, the temperature of the mixture being between Tmin and Tmax; wherein
xsolute is the mole fraction of dissolved solute in a saturated two component mixture of solute and solvent at a temperature, T;
Tm(solute) is the normal melting temperature of the solute;
Tmin is a temperature where the second derivative of a function of xsolute with respect to temperature becomes a negative value; and
Tmax is a temperature greater than Tmin and less than (Tmin+0.8(Tm(solute)−Tmin)).

### Claim 46

A process having an operating temperature range, Tmin to Tmax, at which solubility of a non-electrolyte solute in a solvent is maximized, the process comprising forming a mixture comprising the non-electrolyte solute and the solvent, wherein the solubility of the solute in the solvent is less than the ideal solubility at a temperature, T, the temperature of the mixture being between Tmin and Tmax; wherein
wt. %solute is the wt. % of dissolved solute in a saturated two component mixture of solute and solvent at a temperature, T;
Tm(solute) is the normal melting temperature of the solute;
Tmin is a temperature where the second derivative of a function of wt. %solute with respect to temperature changes becomes a negative value; and
Tmax is a temperature greater than Tmin and less than about (Tmin+0.8(Tm(solute)−Tmin)).

### Claim 47 (depends on 44)

The process of claim 44 wherein the non-electrolyte solute comprises an ester or an ether.

### Claim 48 (depends on 47)

The process of claim 47 wherein the ester is selected from compounds having structures corresponding to
(a) Formula 1A,
(b) Formula 2A,
(c) Formula 3A, or
(d) Formula 4A
wherein
R12, R13, R14, R15 and R16 are independently hydrogen, hydrocarbyl, substituted hydrocarbyl, halogen, heterocyclo, alkoxy, alkenoxy, alkynoxy, aryloxy, hydroxy, protected hydroxy, acyl, acyloxy, nitro, amido, cyano, thiol, hydroxycarbonyl or alkoxycarbonyl; and
R10 is substituted or unsubstituted aryl or substituted or unsubstituted C1-C20 straight, branched or cyclic alkyl, alkenyl or alkynyl;
R21 is hydrogen, —COOH, —COOR11, hydrocarbyl, substituted hydrocarbyl, halogen, heterocyclo, alkoxy, alkenoxy, alkynoxy, aryloxy, hydroxy, protected hydroxy, acyl, acyloxy, nitro, amido, cyano, thiol, ketal, or acetal; and
R11 is hydrogen or substituted or unsubstituted aryl or C1-C20 straight, branched or cyclic alkyl, alkenyl or alkynyl.

### Claim 49 (depends on 44)

The process of claim 44 wherein Tmax is less than about (Tmin+0.6(Tm(solute)−Tmin)).

### Claim 50 (depends on 49)

The process of claim 49 wherein Tmax is less than about (Tmin+0.4(Tm(solute)−Tmin)).

### Claim 51 (depends on 50)

The process of claim 50 wherein Tmax is less than about (Tmin+0.2(Tm(solute)−Tmin)).

### Claim 52

A process for preparing an ester from a carboxylic acid comprising
(a) reacting a carboxylic acid substrate with an alcohol to form a reaction mixture comprising the carboxylic acid substrate, the alcohol, and the ester wherein at least about 25% of the carboxylic acid substrate measured on a molar basis is converted to the ester;
(b) adding solid acid catalyst and contacting the reaction mixture with the solid acid catalyst to form a reaction product comprising the ester wherein at least about 97% of the carboxylic acid substrate measured on a molar basis is converted to ester.

### Claim 53 (depends on 52)

The process of claim 52 further comprising
(c) crystallizing the reaction product and separating the crystallized reaction product from the reaction mixture.

### Claim 54 (depends on 52)

The process of claim 52 wherein solid acid catalyst is added at step (a) and the ratio of the amount of the solid acid catalyst added in step (b) to the amount of the solid acid catalyst added in step (a) is greater than about 1:1.

### Claim 55 (depends on 54)

The process of claim 54 wherein solid acid catalyst is added at step (a) and the ratio of the amount of the solid acid catalyst added in step (b) to the amount of the solid acid catalyst added in step (a) is greater than about 10:1.

### Claim 56 (depends on 52)

The process of claim 52 wherein the carboxylic acid substrate and corresponding product ester are selected from compounds having structures corresponding to
(a) Formula 1 and 1A, respectively,
(b) Formula 2 and 2A, respectively,
(c) Formula 3 and 3A, respectively, or
(d) Formula 4 and 4A, respectively
wherein
R12, R13, R14, R15 and R16 are independently hydrogen, hydrocarbyl, substituted hydrocarbyl, halogen, heterocyclo, alkoxy, alkenoxy, alkynoxy, aryloxy, hydroxy, protected hydroxy, acyl, acyloxy, nitro, amino, amido, cyano, thiol, hydroxycarbonyl or alkoxycarbonyl; and
R10 is aryl or substituted or unsubstituted C1-C20 straight, branched or cyclic alkyl, alkenyl or alkynyl;
R21 is hydrogen, —COOH, —COOR11, hydrocarbyl, substituted hydrocarbyl, halogen, heterocyclo, alkoxy, alkenoxy, alkynoxy, aryloxy, hydroxy, protected hydroxy, acyl, acyloxy, nitro, amido, cyano, thiol, ketal, or acetal; and
R11 is substituted or unsubstituted aryl or C1-C20 straight, branched or cyclic alkyl, alkenyl or alkynyl.

### Claim 57 (depends on 52)

The process of claim 52 wherein the alcohol has the formula of R22OH wherein R22 is C1-C20 straight, branched or cyclic alkyl.

### Claim 58 (depends on 52)

The process of claim 52 wherein the solid acid catalyst is a strong acid cation exchange resin.

### Claim 59 (depends on 52)

The process of claim 52 wherein the conversion is carried out at a temperature from about Tmin to about Tmax;
wherein Tmin is a temperature, in K, where an absolute value of γsolute is greater than one and less than about 10 and the second derivative of a function of γsolute with respect to temperature becomes a positive value; and
Tmax is a temperature, in K, which is greater than Tmin and less than (Tmin+0.8(Tm(solute)−Tmin));
wherein γsolute is the activity coefficient of the solute in a two component mixture of the solute in the solvent at a temperature, T, derived from equation (5);
ln


γ
solute

x
solute
=
-
Δ


H
solute
F
R

(
1
T
-
1
T
m

(
solute
)
)
(
5
)
xsolute is the mole fraction of dissolved solute in a saturated two component mixture of solute and solvent at a temperature, T, in K;
R is the ideal gas constant in cal/K·mol;
−ΔHFsolute is the heat of fusion in cal/g·mol of the solute; and Tm(solute) is the absolute melting temperature of the solute, in K.

### Claim 60 (depends on 52)

The process of claim 52 further comprising
drying the reaction mixture by contacting the reaction mixture with dry alcohol vapor wherein the water content (in wt. %) of dry alcohol vapor is less than the water content of the vapor (in wt. %) in equilibrium with the reaction mixture; and
feeding the dry alcohol vapor to a knockback condenser to separate a dialkyl ether byproduct from the alcohol, wherein the amount of the dialkyl ether byproduct in the reaction mixture is less than about 0.3 wt. %.

### Claim 61 (depends on 60)

The process of claim 60 wherein the reaction mixture is dried by contacting it with the dry alcohol vapor via countercurrent flow.

### Claim 62 (depends on 60)

The process of claim 60 wherein the water content (in wt. %) of dry alcohol vapor is about 50% less than the water content of the vapor (in wt. %) in equilibrium with the reaction mixture.

### Claim 63 (depends on 60)

The process of claim 60 wherein the reaction mixture is removed from contact with the solid acid catalyst.

### Claim 64

A process for separating a mixture of an alcohol, an ether and water, the process comprising:
introducing an aqueous mixture of an alcohol and an ether into a distillation column;
separating the mixture to produce water and a vapor comprising the ether and the alcohol;
introducing the vapor exiting an upper portion of the column into a lower portion of a knockback condenser; and
condensing the vapor in the knockback condenser to form an ether-rich vapor exiting an upper portion of the knockback condenser and an alcohol-rich liquid exiting the lower portion of the knockback condenser, wherein the ether-rich vapor contains at least about 50 wt. % of the ether in the mixture.

### Claim 65 (depends on 64)

The process of claim 64 wherein the ether-rich vapor contains at least about 60 wt. % of the ether in the mixture.

### Claim 66 (depends on 64)

The process of claim 64 wherein the alcohol-rich liquid is recycled to the upper portion of the column.

### Claim 67 (depends on 64)

The process of claim 64 wherein the alcohol is methanol.

### Claim 68 (depends on 64)

The process of claim 64 wherein the ether is dimethyl ether.