WO1999021825A1

WO1999021825A1 - Hydroxy fatty acid saccharide amides

Info

Publication number: WO1999021825A1
Application number: PCT/US1998/022722
Authority: WO
Inventors: Hans B. Frykman; Terry A. Isbell
Original assignee: The United States Of America, As Represented By The Secretary Of Agriculture
Priority date: 1997-10-27
Filing date: 1998-10-27
Publication date: 1999-05-06
Also published as: AU1122999A

Abstract

Novel 5-monohydroxy fatty acid amides are described which may be used as biodegradable surfactants in detergents, soaps, cosmetics, foods, pharmaceuticals, and polymers. The compounds of this invention are of formula (I) wherein R1 is selected from C¿2?-C17 hydrocarbons which may be saturated or unsaturated, or branched or straight chain, R?2¿ is selected from H and C¿1?-C20 hydrocarbons which may be saturated or unsaturated, branched or straight chain, and optionally substituted with one or more alkoxy or hydroxy groups, R?3¿ is selected from open chain mono- or polyhydroxy hydrocarbons, and R4 is selected from the group consisting of H and mono- or polyhydroxy hydrocarbons. In the preferred embodiment, the compound is a 5-monohydroxy fatty acid saccharide amide, wherein the combined -R3-O-R4 moiety is derived from a mono- or oligosaccharide. The 5-monohydroxy fatty acid amides may be produced in the absence of a solvent and in high yields by reaction of fatty acid δ-lactones with an aminated mono- or polyhydroxy hydrocarbon. The reaction may be conducted substantially in the absence of a solvent and with high yields, even when reacting the δ-lactones with saccharide amines having a short chain hydrocarbon functional group.

Description

HYDROXY FATTY ACID SACCHARIDE AMIDES

Background of the Invention Field of the Invention

This invention relates to novel 5-monohydroxy fatty acid amides useful as surfactants and a process for their production. Description of the Prior Art

Meadowfoam oil and its fatty acids have been used recently in the development of novel materials having a variety of industrial applications. The oil has been vulcanized and the resultant factice has exhibited good properties in rubber applications as described by Erhan and Kleiman (1990, J. Am. Oil Chem. Soc, 67:670-674; 1990, Rubber World, 203:33-36; and 1993, J. Am. Oil Chem. Soc, 70:309-311). The meadowfoam fatty acids have been converted into amides (Burg and Kleiman, 1991, J. Am. Oil Chem. Soc, 68:190-192), dimer acids (Burg and Kleiman, 1991, J. Am. Oil Chem. Soc, 68:600-603), and estolides, which may also be hydrolyzed to hydroxy fatty acids (Erhan et al . , 1993, J. Am. Oil Chem. Soc, 70:461-465; and Burg et al . , U.S. Patent no. 5,380,894). More recently, the production of δ-lactones from the Δ⁵ unsaturated fatty acids of meadowfoam oil has been described (Isbell and Kleiman, 21st World Congress and Exhibition of the International Society for Fat Research, October 1-5, 1995, The Hague, Netherlands) .

Summary of the Invention We have now invented novel 5-monohydroxy fatty acid amides for use as biodegradable surfactants in detergents, soaps, cosmetics, foods, pharmaceuticals, and polymers. In the preferred embodiment, the compound is a 5-monohydroxy fatty acid saccharide amide, wherein the combined -R³-0-R⁴ moiety is derived from a mono- or oligosaccharide . We have also invented a novel process of producing 5-monohydroxy fatty acid amides in the absence of a solvent and in high yields. One or more non-hydroxylated fatty acid δ-lactones may be reacted with an aminated mono- or polyhydroxy hydrocarbon under conditions and for a period of time effective to form the 5-monohydroxy fatty acid. Surprisingly, the reaction may be conducted substantially in the absence of a solvent and with high yields, even when reacting the δ-lactones with saccharide amines having a short chain hydrocarbon functional group .

In accordance with this discovery, it is an object of this invention to provide novel hydroxy fatty acid amides having utility as biodegradable surfactants .

It is a further object of the invention to provide novel hydroxy fatty acid saccharide amides having utility as biodegradable surfactants .

Another object of the invention is to provide a method for producing the hydroxy fatty acid amides in high yields .

Other objects and advantages of this invention will become readily apparent from the ensuing description.

Detailed Description of the Invention

The compounds of this invention are 5-monohydroxy fatty acid amides of the formula:

OH 0 R

(I)

R^X-CH- (CH₂) ,-C-N-R³-0-R⁴

wherein R¹ is selected from C₂-C₁₇ hydrocarbons (non-hydroxylated) which may be saturated or unsaturated, or branched or straight chain, R² is selected from H and C^-C^ hydrocarbons which may be saturated or unsaturated, branched or straight chain, and optionally substituted with one or more oxy, alkoxy, or hydroxy groups, R³ is selected from open chain (linear) mono- or polyhydroxy hydrocarbons, and R⁴ is selected from H, or mono- or polyhydroxy hydrocarbons . In accordance with the preferred embodiment, the monohydroxy fatty acid component of the compound, R¹-CHOH- (CH₂) ₃-C0- , is derived from commercially available unsaturated fatty acids in the manner described in greater detail hereinbelow. Consequently, R¹ is preferably a C_1X, C₁₃, C₁₅, or C₁₇ hydrocarbon, with C₁₃ and C₁₅ hydrocarbons being particularly preferred.

The -R³-0-R⁴ component of the amide is preferably derived from commercially available monosaccharides or oligosaccharides, also as described in greater detail below. Accordingly, in the preferred embodiment, R³ is selected from the following:

-CH₂- (CHOH) _n-CH₂- and alkoxylated derivatives thereof,

-CH(CH₂0H) - (CHOH^-CH,- and alkoxylated derivatives thereof , and

-CH₂- (CHOH) ₂-CH (-CHOH-CH₂OH) - and alkoxylated derivatives thereof, wherein n is an integer between 1 to 5 , and particularly 1 to 4 , inclusive. Amides wherein n is 3 or 4, and R⁴ is H, a monosaccharide, or an oligosaccharide are particularly preferred, especially those wherein R³ is -CH₂- (CHOH) _n-CH₂- and R⁴ is H. Specific examples of preferred amides include those wherein R³-0- taken together is 1- deoxy-glucosyl, deoxy-sorbitolyl, 1-deoxy- mannosyl, deoxy-mannitolyl, 1-deoxy-galactosyl, 2-deoxy-fructosyl, or 2-deoxy-sorbosyl. Without being limited thereto, monosaccharide and oligosaccharides which are suitable for use as the -R³-0-R⁴ component of the amide of this invention include those described for example, by Connor et al . (U.S. Patent 5,194,639) or Scheibel (U.S. Patent 5,500,150), the contents of each of which are incorporated by reference herein.

A variety of hydrocarbons are suitable for use in the R² functional group, including those described for example, by Connor et al . or Scheibel et al . ( ibid) . However, preferred R² groups include C-. - C₈ hydrocarbons, especially C_x - C₃ hydrocarbons and oxyhydrocarbons . Specific examples of preferred R² moieties include methyl, propyl, hexyl, ethylhexyl, and dimethyl ketone .

In general, the 5-monohydroxy fatty acid amides of this invention are prepared by reaction of a δ-lactone with an aminated mono- or polyhydroxy hydrocarbon, generally an aminated mono- or oligosaccharide. Specifically, a fatty acid δ-lactone of the formula :

i o ₁

I I ⁽ID

R-CH- (CH₂)₃-C=0

wherein R is a hydrocarbon which may be saturated or unsaturated, or branched or straight chain, is reacted with a polyhydroxy amine, preferably a saccharide amine, of the formula:

R²

I (III)

H-N-R³-0-R⁴

wherein R², R³, and R⁴ are as described above, under conditions and for a period of time effective to form the 5-monohydroxy fatty acid saccharide amide of formula (I) .

Because of the relatively high reactivity of the δ-lactone, reaction conditions are typically mild and use of a catalyst is optional. Generally, the reaction may be conducted with agitation over a wide temperature range between about 20 to 130°C, although a temperature of about 90°C is preferred. Suitable catalysts include a variety of bases, including but not limited to, small trialkyl amines and pyridine . Use of a solvent, which may be either organic or non-organic, is also optional. If present, examples of suitable solvents include organic alcohols such as t- butanol. As illustrated in the examples, the time of reaction may vary significantly with the starting materials, choice of solvent and/or catalyst, and temperature. Using the process described hereinabove, reaction yields of 5-monohydroxy fatty acid amides greater than 50% have been readily obtained, with yields ranging from 50 to 97% after reactions between 16 and 130 hours.

In a particularly preferred embodiment, we have unexpectedly found that high yields of 5-monohydroxy fatty acid amides may be obtained by reaction of a δ-lactone with saccharide amines having a short chain hydrocarbon functional group in the absence of a solvent. These saccharide amines are surprisingly soluble in the δ-lactones. Specifically, when reacting the δ-lactones with a saccharide amine of formula III wherein R² is a C_lf C₂ or C₃ hydrocarbon, in the absence of a solvent, reaction yields in excess of 70% may be readily obtained; yields greater than 90% may even be obtained in the absence of a solvent when R² is a C hydrocarbon .

Following the reaction, the 5-monohydroxy fatty acid amides may be recovered by solvent extraction. By way of example, the product amide may be first separated from residual amine by dissolving the reaction product in a suitable solvent, such as methanol, and crystallizing at -25 or -80°C until crystals are formed. The crystals, which are usually white or brown, may be recovered by filtration and dried. The amides may be further purified and separated from residual lactone and fatty acid by dissolving the recovered crystals in a second solvent, such as hexane, followed by a crystallization, filtration and drying in the same manner as described above. If the reaction is conducted in the presence of a solvent, it should be first removed in vacuo prior to extraction.

The δ-lactones and aminated mono- or polyhydroxy hydrocarbons used as starting materials in the production of the 5-hydroxy amides may be produced using previously described techniques . The δ-lactones, for instance, may be produced from unsaturated fatty acids using the process described by Isbell and Plattner, U.S. Patent application serial no. 08/534,810, the contents of which are incorporated by reference herein. While this process was described for the production of the δ-lactones from Δ⁵ and Δ⁶ fatty acids such as found in meadowfoam oil, it may also be used to produce the δ-lactones from a variety of other unsaturated fatty acids as well, particularly Δ⁹ and Δ¹³ fatty acids. Preferred unsaturated fatty acids for use herein include free and esterified Δ⁵, Δ⁶, Δ⁹, or Δ¹³ fatty acids, particularly 5-eicosenoic acid (20:1 Δ⁵) , 5-docosenoic acid (22:1 Δ⁵) , 5 , 13-docosadienoic acid (22:2, Δ⁵'¹³) , petroselinic acid (16:1 Δ⁶) , oleic acid (18:1 Δ⁹) , palmitoleic acid (16:1 Δ⁹) , and erucic acid (22:1 Δ¹³) .

In review, the δ-lactones are formed by reacting the unsaturated fatty acid in the presence of an effective amount of an acidic catalyst such as HC10₄ or H₂S0₄, usually at a temperature between about 20 to 50°C. In the preferred embodiment, the unsaturated fatty acids are provided in a non-aqueous solvent having a relatively high dielectric constant, such as cyclohexane, t-butanol, CH₂C1₂, or CHC1₃, and the concentration of the catalyst should be between about 0.5 to 10 molar equivalents.

The aminated mono- or polyhydroxy hydrocarbons, and aminated saccharides in particular, may be obtained from commercial sources or produced by a conventional reductive amination reaction of the hydroxylated hydrocarbon. Preferred hydroxylated hydrocarbons for use herein include mono- or oligosaccharides, particularly glucose, sorbitol, mannose, mannitol, galactose, fructose, and sorbose. Briefly, the hydroxylated hydrocarbon or saccharide, R⁴- 0-R³=0 is reacted with an amine, NH₃ or NH₂R², in a suitable solvent, such as methanol, in the presence of an effective amount of a Pt/C catalyst . Preferred reaction conditions include a temperature of between room temperature and about 90°C for 1-12 hours at 1,000 psi H₂. Solid amine may be recovered by evaporation of the solvent. Alternative reactions suitable for use herein are also described by Scheibel et al . (U.S. Patent 5,500,150) .

The 5-monohydroxy fatty acid amides produced in accordance with this invention may be used as surfactants in detergents, soaps, cosmetics, foods, pharmaceuticals, and polymers.

The following examples are intended only to further limit the scope of the subject matter which is defined by the claims.

Example 1

4.0032 g (14.19 mmol) of δ-stearolactone and 2.7765 g (14.22 mmol) of N-methyl-D-glucamine were mixed at 90°C, using a mechanical stirrer in a water heated reactor. The reaction was stopped after 16 hours to yield a white colored product . This product was dissolved in 1-6 equivalents of methanol and allowed to crystallize at -25 or -80°C until white crystals were formed. The crystals were filtered and dried, then dissolved in 1-5 equivalents of hexane, and again allowed to crystallize at -25 or -80°C until white crystals were formed. The resultant crystals were again filtered and dried.

HPLC analysis of the crystalline product revealed a 97% yield of 5-monohydroxy stero-N-methyl-glucamide . Product identity was confirmed by NMR and microanalysis .

Example 2

3.0086 g (9.72 mmol) of δ-eicosanoic lactone and 2.85 g (9.73 mmol) of N-2-ethylhexyl-D-glucamine were dissolved in 50 ml t- butanol in a 100 ml round bottom flask. The reaction mixture was refluxed for 130 hours using a magnetic stirrer. After 130 hours, the reaction was stopped and t-butanol solvent was removed in vacuo . The remaining reaction product was purified in the same manner described in Example 1. HPLC analysis of the crystalline product revealed a 52% yield of 5-monohydroxy eicosano-N-2-ethylhexyl-glucamide . Product identity was confirmed by NMR and microanalysis .

Example 3

1 g (3.23 mmol) of δ-eicosanolactone and 0.7074 g (3.23 mmol) of N-propyl-D-glucamine were mixed at 90°C, using a mechanical stirrer in a water heated reactor. The reaction was stopped after 18 hours to yield a brown colored product. This product was purified as described in Example 1.

HPLC analysis of the crystalline product revealed a 76% yield of 5-monohydroxy eicosano-N-propyl-glucamide . Product identity was confirmed by NMR and microanalysis .

Example 4

1.58 g (5.12 mmol) of δ-eicosanoic lactone and 1 g (5.12 mmol) of N-methyl-D-glucamine were dissolved in 20 ml t-butanol in a 100 ml round bottom flask. The reaction mixture was refluxed for 64 hours using a magnetic stirrer, yielding a brown colored product. After 64 hours, the reaction was stopped and t-butanol solvent was removed in vacuo. The remaining reaction product was purified in the same manner described in Example 1.

HPLC analysis of the crystalline product revealed a 52% yield of 5-monohydroxy eicosano-N-methyl-glucamide . Product identity was confirmed by NMR and microanalysis.

Example 5

1.556 g (5.52 mmol) of δ-sterolactone and 1 g (5.52 mmol) of 1-amino-l-deoxy-d-sorbitol were dissolved in 20 ml t-butanol in a 100 ml round bottom flask. The reaction mixture was refluxed for 27 hours using a magnetic stirrer, yielding a brown colored product. After 27 hours, the reaction was stopped and t-butanol solvent was removed in vacuo . The remaining reaction product was purified in the same manner described in Example 1. HPLC analysis of the crystalline product revealed a 92% yield of 5-monohydroxy stero-N-glucamide . Product identity was confirmed by NMR and microanalysis.

Example 6

1.26 g (4.484 mmol) of δ-sterolactone and 1 g (4.484 mmol) of N-propyl-D-glucamine were mixed at 90°C, using a mechanical stirrer in a water heated reactor. The reaction was stopped after 44 hours to yield a white colored product . This product was purified as described in Example 1.

HPLC analysis of the crystalline product revealed a 69% yield of 5-monohydroxy stero-N-propyl-glucamide . Product identity was confirmed by NMR and microanalysis.

It is understood that the foregoing detailed description is given merely by way of illustration and that modifications and variations may be made therein without departing from the spirit and scope of the invention.

Claims

We claim :

1. A 5-monohydroxy fatty acid amides of the formula:

OH 0 R² R'-CH- (CH₂) ₃-C-N-R³-0-R⁴

wherein R¹ is selected from C₂-C₁₇ hydrocarbons which may be saturated or unsaturated, branched or straight chain, R² is selected from the group consisting of H and C^C^ hydrocarbons which may be saturated or unsaturated, branched or straight chain, and optionally substituted with one or more, oxy, alkoxy or hydroxy groups, R³ is selected from open chain mono- or polyhydroxy hydrocarbons, and R⁴ is selected from the group consisting of H and mono- or polyhydroxy hydrocarbons.

2. The 5-monohydroxy fatty acid amide of claim 1 wherein R¹ is selected from the group consisting of C_11# C₁₃, C_1S, and C₁₇ hydrocarbons .

3. The 5-monohydroxy fatty acid amide of claim 2 wherein R¹ is selected from the group consisting of C₁₃ and C_1S hydrocarbons .

4. The 5-monohydroxy fatty acid amide of claim 1 wherein R² is selected from the group consisting of C_1# C₃, and C₈ hydrocarbons .

5. The 5-monohydroxy fatty acid amide of claim 1 wherein R³ is a C₃-C₆ hydrocarbon having one to four hydroxy groups.

6. The 5-monohydroxy fatty acid amide of claim 1 wherein R³ is selected from the group consisting of:

-CH₂- (CH0H)_n-CH₂- and alkoxylated derivatives thereof, -CT(C╬ù₂OH)-(CHOH)_n_₁-CH₂- and alkoxylated derivatives thereof , and

-CH₂- (CHOH) ₂-CH(-CHOH-CH₂0H) - and alkoxylated derivatives thereof , wherein n is an integer between 1 to 5 , inclusive.

7. The 5-monohydroxy fatty acid amide of claim 6 wherein n is 3 or 4 and R⁴ is selected from the group consisting of H and monosaccharides .

8. The 5-monohydroxy fatty acid amide of claim 7 wherein R³ is -CH₂- (CHOH)_n-CH₂- and R⁴ is H.

9. The 5-monohydroxy fatty acid amide of claim 1 wherein R³-0- taken together is selected from the group consisting of 1- deoxy-glucosyl, deoxy-sorbitolyl, 1-deoxy-mannosyl, deoxy- mannitolyl, 1-deoxy-galactosyl, 2-deoxy-fructosyl, and 2-deoxy- sorbosyl .

10. The 5-monohydroxy fatty acid amide of claim 1 wherein R⁴ is selected from the group consisting of H, monosaccharides, and oligosaccharides

11. A process for the production of 5-hydroxy fatty acid amides comprising reacting one or more non-hydroxy fatty acid ╬┤- lactones of the formula : i o 1

I I

R-CH- (CH,)₃-C=0 wherein R is a hydrocarbon which may be saturated or unsaturated, or branched or straight chain, with an amine of the formula:

R^*

H-N-R-O-R⁴

wherein R² is selected from C_x-C₃ hydrocarbons which may be saturated or unsaturated, branched or straight chain, and optionally substituted with one or more oxy, alkoxy or hydroxy groups, R³ is selected from open chain mono- or polyhydroxy hydrocarbons, and R⁴ is selected from the group consisting of H and mono- or polyhydroxy hydrocarbons, substantially in the absence of a solvent and under conditions and for a period of time effective to form a 5-monohydroxy fatty acid amide of the formula: OH 0 R²

R^X-CH- (CH₂) ₃-C-N-R³-0-R⁴

wherein R¹ is selected from C₂-C₁₇ hydrocarbons which may be saturated or unsaturated, branched or straight chain.

12. The process of claim 11 wherein R² is a C_x hydrocarbon.

13. The process of claim 11 wherein R³ is a C₃-C₃ hydrocarbon having one to four hydroxy groups .

14. The process of claim 11 wherein R³ is selected from the group consisting of:

-CH₂- (CH0H)_n-CH₂- and alkoxylated derivatives thereof,

-CH(CH₂0H) - (CHOH)_n._x-CH₂- and alkoxylated derivatives thereof , and

-CH₂- (CHOH) ₂-CH(-CHOH-CH₂OH) - and alkoxylated derivatives thereof, wherein n is an integer between 1 to 5 , inclusive.

15. The process of claim 14 wherein n is 3 or 4 and R⁴ is selected from the group consisting of H and monosaccharides.

16. The process of claim 15 wherein R³ is -CH₂- (CHOH) _n-CH₂- and R⁴ is H.

17. The process of claim 11 wherein R³-0- taken together is selected from the group consisting of 1- deoxy-glucosyl, deoxy- sorbitolyl, 1-deoxy-mannosyl, deoxy-mannitolyl , 1-deoxy- galactosyl, 2-deoxy-fructosyl, and 2-deoxy-sorbosyl .

18. The process of claim 11 wherein R¹ is selected from the group consisting of C_X1, C₁₃, C₁₅, and C₁₇ hydrocarbons.

19. The process of claim 18 wherein R¹ is selected from the group consisting of C₁₃ and C₁₅ hydrocarbons .