Synthesis of triethylene glycol bis(2-ethylhexanoate)

Abstract

A process for the transesterification of methyl-2-ethylhexanoate with triethylene glycol to produce triethylene glycol di-2-ethylhexanoate is provided. In the process, methyl-2-ethylhexanoate is combined with triethylene glycol to form a first mixture. The first mixture is heated in the presence of a catalyst to form a second mixture comprising methanol and triethylene glycol di-2-ethylhexanoate. Methanol is separated from the second mixture to yield triethylene glycol di-2-ethylhexanoate. Na.sub.2CO.sub.3, Cs.sub.2CO.sub.3, K.sub.2CO.sub.3, Rb.sub.2CO.sub.3, sodium methoxide or titanium isopropoxide are suitable catalysts.

Claims

1. A process for preparing triethyleneglycol di-2-ethylhexanoate comprising: a) combining methyl-2-ethylhexanoate, triethylene glycol, and a catalyst to form a first mixture; b) heating the first mixture to form a second mixture comprising methanol and triethyleneglycol di-2-ethylhexanoate; and c) separating methanol from the second mixture to yield triethyleneglycol di-2-ethylhexanoate wherein the catalyst is a Group I carbonate salt, and wherein the triethyleneglycol di-2-ethylhexanoate yield is at least 90%.

2. The process of claim 1 wherein the catalyst is selected from the group consisting of Na.sub.2CO.sub.3, Cs.sub.2CO.sub.3, K.sub.2CO.sub.3, and Rb.sub.2CO.sub.3.

3. The process of claim 1 wherein step b) is conducted at a temperature of about 100 C. to about 180 C. for about 2 hours to about 8 hours.

4. The process of claim 1 further comprising the step of washing the catalyst from said triethyleneglycol di-2-ethylhexanoate with water after step c).

5. The process of claim 1 wherein the molar ratio of methyl-2-ethylhexanoate to triethylene glycol in said first mixture is from 1:1 to 3:1.

6. The process of claim 1 wherein the molar amount of the catalyst in said first mixture is from about 1 mole percent to about 5 mole percent.

7. A process for preparing triethyleneglycol di-2-ethylhexanoate (TEG-2EH) comprising: a) combining methyl-2-ethylhexanoate, triethylene glycol, and a catalyst selected from the group consisting of Cs.sub.2CO.sub.3 and K.sub.2CO.sub.3 to form a first mixture; b) heating the first mixture at a temperature of about 100 C. to about 180 C. for about 2 hours to about 8 hours to form a second mixture comprising methanol and TEG-2EH; and c) separating methanol from the second mixture to yield TEG-2EH wherein the TEG-2EH yield is at least 90%.

8. The process of claim 7 further comprising the step of washing the catalyst from said triethyleneglycol di-2-ethylhexanoate with water after step c).

9. The process of claim 7 wherein the molar ratio of methyl-2-ethylhexanoate to triethylene glycol in said first mixture is from 1:1 to 3:1.

10. The process of claim 7 wherein the molar amount of the catalyst in said first mixture is from about 1 mole percent to about 5 mole percent.

11. The process of claim 7 wherein step b is conducted at a temperature of about 135 C. to about 165 C.

12. A process for preparing triethyleneglycol di-2-ethylhexanoate comprising: a) combining methyl-2-ethylhexanoate, triethylene glycol, and a catalyst to form a first mixture; b) heating the first mixture form a second mixture comprising methanol and triethyleneglycol di-2-ethylhexanoate; and c) separating methanol from the second mixture to yield triethyleneglycol di-2-ethylhexanoate; wherein said catalyst is selected from the group consisting of Na.sub.2CO.sub.3, Cs.sub.2CO.sub.3, and K.sub.2CO.sub.3, and wherein the triethyleneglycol di-2-ethylhexanoate yield is at least 90%.

13. The process of claim 12 wherein step b) is conducted at a temperature of about 100 C. to about 180 C. for about 2 hours to about 8 hours.

14. The process of claim 12 further comprising the step of washing catalyst from said triethyleneglycol di-2-ethylhexanoate with water after step c).

15. The process of claim 12 wherein the molar ratio of methyl-2-ethylhexanoate to triethylene glycol in said first mixture is from 1:1 to 3:1.

Description

DETAILED DESCRIPTION OF THE INVENTION

(1) As used herein the following terms have the meaning as defined below:

(2) The term M2EH refers to methyl-2-ethylhexanoate.

(3) The term TEG refers to triethylene glycol.

(4) The term TEG-2EH refers to triethylene glycol di-2-ethylhexanoate.

(5) The term MeOH refers to methanol.

(6) The term Ti(OiPr).sub.4 refers to titanium isopropoxide (Ti[OCH(CH.sub.3).sub.2].sub.4)

(7) The abbreviation wt % means weight percent.

(8) The abbreviation mol % means mole percent.

(9) As used herein, the indefinite articles a and an mean one or more, unless the context clearly suggests otherwise. Similarly, the singular form of nouns includes their plural form, and vice versa, unless the context clearly suggests otherwise.

(10) While attempts have been made to be precise, the numerical values and ranges described herein should be considered to be approximations (even when not qualified by the term about). These values and ranges may vary from their stated numbers depending upon the desired properties sought to be obtained by the present invention as well as the variations resulting from the standard deviation found in the measuring techniques. Moreover, the ranges described herein are intended and specifically contemplated to include all sub-ranges and values within the stated ranges. For example, a range of 0 to 100 is intended to describe and include all values within the range including sub-ranges such as 0.1 to 99.9, 1 to 99, 50-100, 60 to 90 and 70 to 80.

(11) It has been surprisingly discovered that an efficient method to form a variety of methyl esters is via direct coupling of oxo aldehydes with methanol in the presence of Shvo's catalyst (Equation (1)).

(12) ##STR00001##

Shvo's Catalyst

(13) Shvo's catalyst (1-Hydroxytetraphenyl-cyclopentadienyl(tetraphenyl-2,4-cyclopentadien-1-one)-mu-hydrotetracarbonyldiruthenium(II)) is available commercially from Millipore Sigma.

(14) ##STR00002##

(15) The yields and selectivities for these reactions were found to be excellent and generally fall within 95-99%. Of particular interest, is the reaction between 2-ethylhexanal and methanol to produce methyl-2-ethylhexanoate in 99.5% yield and high selectivity. This discovery has allowed us to consider a new route that employs a transesterification reaction between methyl-2-ethylhexanoate and triethylene glycol to produce triethylene glycol di-2-ethylhexanoate (TEG-2EH) as the product (Equation (2)). Low-boiling methanol is the sole byproduct of this reaction and therefore it is possible to thermodynamically drive the reaction to completion by continuously removing methanol from the reaction system.

(16) We examined a variety of readily available catalysts to carry out the transesterification reaction between methyl-2-ethylhexanoate and triethylene glycol. The formation of TEG-2EH occurs in two steps: one equivalent of methyl-2-ethylhexanoate reacts with triethylene glycol to afford TEG-2EH monoester (Equation (3)) and the second equivalent of methyl-2-ethylhexanoate further reacts with the monoester to yield desired TEG-2EH diester (Equation (4)).

(17) In some embodiments of this invention suitable catalysts include carbonate salts. In some embodiments of this invention, suitable catalysts include Na.sub.2CO.sub.3, Cs.sub.2CO.sub.3, K.sub.2CO.sub.3, Rb.sub.2CO.sub.3, sodium methoxide and titanium isopropoxide and mixtures thereof.

(18) The temperature conducive for the TEG-2EH reaction may range, for example, from 100 to 180 C., 105 to 180 C., 110 to 180 C., 120 to 180 C., 125 to 180 C., 130 to 180 C., 135 to 180 C., 140 to 180 C., 100 to 175 C., 100 to 170 C., 100 to 165 C., 120 to 165 C., 125 to 165 C., 130 to 165 C., or 135 to 165 C.

(19) The pressure at which the transesterification reaction may be carried out is not particularly limiting. For example, the pressure may range from atmospheric to 2 MPa. The reaction may be performed in an open reactor where the produced methanol may be withdrawn as the reaction proceeds. Alternatively, the reaction may be performed in a sealed reactor where the produced methanol remains in the reactor.

(20) Preferably, the transesterification reaction is carried out in the absence of water.

(21) The transesterification reaction may be conducted in the presence or absence of an organic solvent. Suitable solvents include aromatic and alkylaromatic solvents such as benzene, toluene and or xylenes, C.sub.9-C.sub.11 aromatics mixtures, substituted aromatics such as anisole, benzonitrile, or diphenyl ether, ethers of ethylene glycol such as diglyme, triglyme, or tetraglyme. Cyclic ethers such as tetrahydrofuran or dioxane may also be used. Saturated hydrocarbons such as cyclohexane, hexanes, heptane or octanes or chlorinated hydrocarbons such as chlorobenzene, dichlorobenzenes, dichloroethane, trichloroethylene and the like may also be used. Carboxylic acids, esters or alcohols are not preferred as they can complicate transesterification equilibria. Likewise, carboxylic amide solvents such as dimethyl acetamide or dimethyl formamide are also not preferred.

(22) The transesterification reaction can take place with catalyst loadings of about 1 to 5 mole percent.

(23) Methanol is readily separated from the reaction liquids by distillation, condensed and purified for alternative uses. These operations may be carried out in a batch or continuous mode.

(24) The TEG-2EH recovered from the methanol TEG-2EH reaction mixture may be washed with water to remove the catalyst.

(25) The process according to the invention can produce TEG-2EH with yields of at least 90%, at least 95% or at least 99%. The reaction times in which these yields may be achieved include, 8 hours or less, 7 hours or less, 6 hours or less, 5 hours or less, 4 hours or less, 3 hours or less, 2 hours or less, or 1 hour or less.

(26) The present invention includes and expressly contemplates any and all combinations of embodiments, features, characteristics, parameters, and/or ranges disclosed herein. That is, the invention may be defined by any combination of embodiments, features, characteristics, parameters, and/or ranges mentioned herein.

(27) This invention can be further illustrated by the following examples of preferred embodiments thereof, although it will be understood that these examples are included merely for purposes of illustration and are not intended to limit the scope of the invention unless otherwise specifically indicated.

EXAMPLES

Synthesis of methyl-2-ethylhexanoate

(28) Anhydrous methanol (47.4 mole, 1523 grams) was added to a 5 L vessel and brought to 3.5 C. while stirring under a N.sub.2 sparge. N-propanol (250 mL) was added to the collection trap and placed in a dry ice Dewar. 2-ethylhexanoyl chloride (1.46 mole, 237.5 grams) was added to a funnel and added dropwise to methanol under positive N.sub.2 pressure over 20 min. Upon addition of all of the 2-ethylhexanoyl chloride (8.76 mole, 1425 grams) the vessel was allowed to stir overnight at room temperature under N.sub.2 sparge. Half of the reaction mixture was transferred to a 5 L separatory funnel and washed twice with 2 L deionized water. This step was repeated, and the remaining mixture and all organics were transferred to a 3 L three neck flask equipped with thermowell, glass stopper, ten plate older Shaw column with L/L distillation head with magnetic reflux arm, condenser, and fraction take off arm. The mixture was brought to reflux at 135 torr and a reflux rate of 2. After discarding the first ten percent, methyl-2-ethylhexanoate (99.8% purity by GC) was collected.

Example 1. Brnsted Acid-Catalyzed Transesterification Between M2EH and TEG

(29) A four-neck round-bottom flask equipped with a magnetic stirrer, N2 purge line, sampling port and a condenser was charged with methyl-2-ethylhexanoate (0.284 mole, 10 eq, 45 gram), TEG (0.0284 mole, 4.27 gram), and an acid catalyst (1.42 millimole, 0.270 gram). The resulting two-phase mixture was heated using a pre-heated oil-bath. As the reaction progressed, the two-phase system began to disappear, and a dark brown colored one-phase solution formed. This reaction mixture was analyzed by gas chromatography and weight percent values for different analytes were obtained from GC analysis. A Brnsted acid, p-toluenesulfonic acid (PTSA), catalyzed the formation of TEG-2EH. When methyl-2-ethylhexanoate and TEG were mixed in a relative mole ratio of 10:1 and the resulting mixture was heated to 138 C. for 6 hours in the presence of 5 mole % of PTSA, TEG-2EH was produced in a high yield (96.3 wt %) and 3.7 wt % of monoester was also generated (Table 1, Run 1). The color of the resulting solution turned dark brown during the course of 6 hours. Note that it is important to produce lightly colored TEG-2EH in order to avoid downstream bleaching process. Furthermore, when PTSA loading was decreased from 5 mol % to 1 mol %, the reactivity dropped significantly and only 52.1 wt % of TEG-2EH was produced after 6 hours. When methyl-2-ethylhexanoate was reacted in the presence of excess of TEG, TEG-2EH monoester was produced exclusively after 4 hours (Run 2). Other Brnsted acids such as 2-ethylhexanoic acid (2-HOEH), and phenol (PhOH) failed to catalyze the transesterification reaction (Runs 3 and 4).

(30) ##STR00003##

(31) TABLE-US-00001 TABLE 1 Reactivity of Brnsted Acid Catalysts. TEG-2EH Catalyst Time Temp. Conv. Mono TEG-2EH Run M2EH:TEG (loading) (h) ( C.) (%) (wt %) (wt %) 1 10:1 PTSA 6 138 90 3.72 96.28 5 mol % 2 1:0 PTSA 4 138 100 100 5 mol % (exclusive) 3 10:1 2-HOEH 22 138 0 0 0 5 mol % 4 10:1 PhOH 24 138 0 0 0 5 mol %

Example 2. Brnsted Base-Catalyzed Transesterification Between M2EH and TEG

(32) As thermal degradation of Brnsted acid catalysts posed challenges, we next turned our attention to Brnsted bases (Table 2). A four-neck round-bottom flask equipped with a magnetic stirrer, N.sub.2 purge line, sampling port and a condenser was charged with methyl-2-ethylhexanoate (0.284 mole, 10 eq, 45 gram), TEG (0.0284 mole, 4.27 gram), and a base catalyst (1.41 millimoel, 0.0767 gram). The resulting two-phase mixture was heated using a pre-heated oil-bath. As the reaction progressed, the two-phase system began to disappear, and a yellow solution resulted. This reaction mixture was analyzed by gas chromatography and weight percent values for different analytes were obtained from GC analysis. When 5 mol % of NaOMe was employed, both TEG-2EH monoester and TEG-2EH were produced with a relative wt % ratio of 69:100 after 6 hours at 138 C. (Run 5). After 22 hours, the relative ratio between monoester and TEG-2EH changed to 56:100 and the color of the solution remained faint yellow.

(33) Although NaOMe showed reactivity, it proceeded with a much slower rate than PTSA.

Example 3. Ti or Ru-Catalyzed Transesterification Between M2EH and TEG

(34) A four-neck round-bottom flask equipped with a magnetic stirrer, N.sub.2 purge line, sampling port and a condenser was charged with methyl-2-ethylhexanoate (0.0852 mole, 3 eq), TEG (0.0284 mole, 4.27 gram), and a Ti or Ru catalyst (1.41 millimole). The resulting two-phase mixture was heated using a pre-heated oil-bath. As the reaction progressed, the two-phase system began to disappear, and a yellow solution resulted. This reaction mixture was analyzed by gas chromatography and weight percent values for different analytes were obtained from GC analysis. With 1 mol % of Cs.sub.2CO.sub.3, quantitative conversion of TEG was achieved and TEG-2EH was produced exclusively (Run 7, Table 2). This reaction was carried out at 160 C. for 4 hours with a slow nitrogen purge to remove methanol from the system. Only a trace amount of TEG-2EH monoester was detected by GC.

(35) ##STR00004##

(36) TABLE-US-00002 TABLE 2 Catalytic Reactivity of Brnsted Bases..sup.a TEG-2EH Catalyst Time Temp. Conv. Mono TEG-2EH Run M2EH:TEG (loading) (h) ( C.) (%) (wt %) (wt %) 5 10:1 NaOMe 6 138 ? 40.97 59.03 5 mol % 6 10:1 NaOMe 22 138 98.34 35.92 64.08 5 mol % 7 3:1 Cs.sub.2CO.sub.3 4 160 100 <0.1 >99.9 2 mol % 8 3:1 K.sub.2CO.sub.3 4 160 100 0.04 99.96 2 mol %

Example 4. K2CO3 (1 mol %), a Carbonate Analogue, was Employed as the Catalyst

(37) A four-neck round-bottom flask equipped with a magnetic stirrer, N.sub.2 purge line, sampling port and a condenser was charged with methyl-2-ethylhexanoate (2.022 mole, 3.03 eq, 320 gram), TEG (0.667 mole, 100 gram), and K2CO3 (13.32 millimole, 1.841 gram). The resulting two-phase mixture was heated using a pre-heated oil-bath. As the reaction progressed (continuous MeOH removal using a distillation head), the two-phase system began to disappear, and a yellow solution resulted. This reaction mixture was analyzed by gas chromatography and weight percent values for different analytes were obtained from GC analysis. This reaction yielded >99 wt % of TEG-2EH after 3.5 hour (Run 8, Table 2)

(38) To demonstrate the feasibility of scaling up this reaction, we carried out the K.sub.2CO.sub.3-catalyzed transestification reaction in a liter scale and successfully reproduced the synthesis of TEG-2EH under such conditions. K.sub.2CO.sub.3 and Cs.sub.2CO.sub.3-catalyzed reactions produced yellowish crude product and when passed through a Celite or Sillica Gel column, the color of the filtrate turned out to be faintly yellow. This indicates that a significant amount of color bodies could be removed by simply filtering the crude product through these materials. As carbonate salts are water soluble and TEG-2EH is insoluble in water, washing of the crude mixture with water could be used as a catalyst separation method.

Example 5

(39) In addition to Brnsted acids and bases, we have also investigated the transesterification reaction in the presence of titanium isopropoxide and Shvo's catalyst (Table 3). While Shvo's complex showed no catalytic activity (Run 9), Ti(OiPr).sub.4 catalyst exhibited excellent reactivity under moisture-free conditions. When 2.7 mol % of Ti(OiPr).sub.4 was employed, TEG-2EH was produced with a high yield (98.9 wt %) and selectivity after 6 hours at 138 C. (Run 10). Best catalytic activity was observed when the titanium catalyst was added at the reaction temperature 138 C. As expected, when wet TEG was used in this reaction, Ti(OiPr).sub.4 reacted with water to form a white residue and the respective yield of TEG-2EH was much lower after 6 h (Run 11).

(40) ##STR00005##

(41) TABLE-US-00003 TABLE 3 Reactivity of Ti(OiPr).sub.4 and Shvo's Catalyst..sup.a TEG-2EH M2EH: Catalyst Time Temp. Conv. Mono TEG-2EH Run TEG (loading) (h) ( C.) (%) (wt %) (wt %) 9 3:1 Shvo 24 160 <5 0 0 5 mol % 10 3:1 Ti(OiPr).sub.4 6 138 100 1.1 98.9 2.7 mol % .sup.11.sup.a 3:1 Ti(OiPr).sub.4 6 138 27 25.8 1.2 2.7 mol % .sup.a10 wt % of water added to TEG.

(42) Best catalytic results have been observed when anhydrous K.sub.2CO.sub.3 was used as the catalyst. With 2 mol % of K.sub.2CO.sub.3 catalyst and a 3:1 mixture of M2EH and TEG, TEG-2EH was produced with a high yield (98.9 wt %) and selectivity after 3.5 hours at 160 C. Only a trace amount of TEG-2EH monoester (0.03 wt %) was detected under this condition. Cs.sub.2CO.sub.3 and Ti(OiPr).sub.4 also turned out to be effective catalysts for this reaction.

(43) In summary, we have discovered that carbonate salts, and in particular, K.sub.2CO.sub.3, efficiently catalyzes the transesterification reaction between methyl-2-ethylhexanoate and TEG to produce TEG-2EH in unprecedentedly high yields and selectivities under mild conditions. Cs.sub.2CO.sub.3 and Ti(OiPr).sub.4 are also effective catalysts for this transformation. Successful employment of carbonate salts offers simple catalyst separation procedures including washing the product with water.

(44) In the specification, there have been disclosed certain embodiments of the invention and, although specific terms are employed, they are used in a generic and descriptive sense only and not for purposes of limitation, the scope of the invention being set forth in the following claims.