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)
RX-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 C1X, 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 Cx - 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 Clf 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.