Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Reexamination Certificate
2001-04-23
2003-11-25
Barts, Samuel (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
C564S017000
Reexamination Certificate
active
06653505
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to novel 1-(3-methoxybenzyl)-3-substituted thiourea compounds and lipid and oil compositions supplemented with such compounds having enhanced oxidative stability.
BACKGROUND OF THE INVENTION
Natural lipids and oils are used in pharmaceutical preparations, food products, cosmetics, and various industrial products such as lubricants, coatings, inks, paints, plastics and the like. Such lipids are subject to oxidative degradation which can affect color, odor, viscosity, and lubricity characteristics thereof, adversely affecting the quality of the commercial products containing such lipids. In the food, cosmetics and pharmaceutical industries, maintaining high quality color and odor of oils and other lipids is important to avoiding oxidation-induced rancidity which is affected by factors such as the oxygen concentration, light and heat, as well as the degree of unsaturation of the lipid or oil, and the amount of natural or synthetic antioxidants present therein. Biodegradable lipids, oils and derivatives thereof used as cutting lubricants are recognized to be adversely affected by heat induced oxidation.
Meadowfoam (
Limnanthes alba
) seed oil has been demonstrated to be highly stable to oxidation. Although the identity of the compound(s) responsible for exceptional oxidative stability of meadowfoam oil is heretofore unknown, mixing meadowfoam oil with other oils imparts enhanced oxidative stability to the mixture. (Isbell, T. A., Abbott, T. A. and Carlson, K. D. 1999. Ind. Crops Prod. 9(2):115-123). Several minor constituents in meadowfoam oil which either diminish oxidative stability or impart small increases in oxidative stability of meadowfoam oil are known, however. (Abbott, T. P. and Isbell, T. A. 1998. Abstracts of the 89th American Oil Chemist's Society Annual Meeting & Expo, Chicago, Ill., May 10-13, 1998. p 66). Refined meadowfoam oil (and other refined seed oils and vegetable oils) exhibit reduced oxidative stability as a result of the refining process. Meadowfoam is known to contain 3-methoxyphenyl actetonitrile, 3-methoxybenzyl isothiocyanate and 3-methoxybenzaldehyde. When added to refined meadowfoam oil at levels from about 0.1% to 1.0%, these compounds exhibit only small to moderate antioxidative effects, at best.
Thiourea has been shown to possess antioxidative activity in oils (Kajimoto and Murakami Nippon Eiyo, Shokuryo Gakkaishi 51(4):207-212, 1998; Chemical Abstract 129:188538); but thiourea is not very soluble in oils. The oxidative stability of ester-based synthetic lubricants (i.e., not vegetable oils) stabilized with amine antioxidants has been shown to be enhanced with specific thioureas (Chao and Kjonaas Amer. Chem. Soc. Preprints, Div. Pet. Chem. 27(2):362-379, 1982). Camenzind and Rolf, Eur. Pat. Appl. EP 91-810474, Chemical Abstract 117:30273, show that certain acylated thioureas are able to increase the oxidative stability to lubricants and hydraulic fluids.
Mono- and di-substituted thiourea compounds also have been described in U.S. Pat. Nos. 2,154,341, 2,662,096, 3,852,348, and 3,991,008. Migirab et al.
Phytochem.
16(11):1719-1721, (1977) disclose methoxy-substituted aromatic thioureas such as N,N′-bis[(4-methoxyphenyl)methyl]-thiourea (CAS #22313-70-8), which is isolated from P. brazzeana.
There is a need for antioxidant compounds and compositions, especially natural antioxidants or derivatives thereof, that are soluble in lipids and oils and are capable of imparting oxidative stability thereto when added at low concentrations.
SUMMARY OF THE INVENTION
We have now unexpectedly discovered that excellent oxidative stability may be imparted to lipids and oils by compounds of the formula I,
wherein R is a C
1
-C
20
linear or branched alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, octyl, decyl, nonyl, dodecyl, and the like, C
5
-C
7
cycloalkyl, such as cyclopentyl, cyclohexyl or cycloheptyl and the like, C
6
-C
7
aryl such as phenyl or benzyl and the like, hydroxy- or alkoxy-substituted C
6
-C
7
aryl such as hydroxyphenyl, methoxyphenyl, ethoxyphenyl, hydroxybenzyl, methoxybenzyl, ethoxybenzyl. Among compounds of the formula I, a presently preferred compound is 1,3-di(3-methoxybenzyl) thiourea, that is a compound of such formula I where R is a 3-methoxybenzyl moiety. An amount of a compound of formula I sufficient to impart oxidative stability to a lipid or oil (or compositions containing such lipids or oils) is from about 0.01 wt. % to about 5.0 wt. % based on the total weight of the lipid or oil.
The present invention also provides oxidatively stable lipid compositions comprising from about 95 wt. % to about 99.99 wt. % of a base lipid or oil and between about 0.01 wt. % and about 5.0 wt. %, more preferably between about 0.05 wt. % and 2.0 wt. %, and most preferably between about 0.1 wt. % and 1.0 wt. % of a compound of formula I. Lipids or oils of the present invention containing between about 3 wt. % and about 5 wt. % or more of a substituted thiourea compound of formula I, based on the total weight of the base lipid or oil composition, may be used as “concentrates” and conveniently added to processed seed oils or other lipids in need of enhanced oxidative stability to provide a lipid or oil composition of the present invention.
The present invention further provides a method for imparting oxidative stability to a base lipid or oil composition in need of enhanced oxidative stability, comprising the step of supplementing a base lipid or oil with an amount of a compound of formula I sufficient to impart enhanced oxidative stability to the base lipid or oil.
Presently preferred compounds of formula I are 1,3-di(3-methoxybenzyl) thiourea; 1-(3-methoxybenzyl)-3-ethyl-2-thiourea; 1-(3-methoxybenzyl)-3-propyl-2-thiourea; 1-(3-methoxybenzyl)-3-hexyl-2-thiourea; 1-(3-methoxybenzyl)-3-dodecyl-2-thiourea; 1-(3-methoxybenzyl)-3-(4-hydroxyphenyl)-2-thiourea; and 1-(3-methoxybenzyl)-3-(3-methoxyphenyl)-2-thiourea. 1,3-di(3-methoxybenzyl) thiourea, which the inventors have identified as a significant natural antioxidant in meadowfoam seed oil, is a particularly preferred compound of the invention.
It also has been surprisingly found that compounds of formula I, in combination with a benzylamine compound such as N-substituted benzylamines, exhibit a synergistic oxidative stabilizing effect in lipids and oils. Various naturally occurring lipids and oils, such as seed oils and vegetable oils contain benzylamine compounds. In these cases, the synergistic effect may be obtained by supplementing such a base lipid or oil with a compound of formula I and, optionally, with an exogenously added benzylamine compound in an amount sufficient to impart yet a further enhancement in oxidative stability. Thus, another aspect of the present invention entails lipid compositions comprising (i) a compound of Formula I and (ii) a benzylamine or N-substituted benzylamine compound to impart enhanced oxidative stability.
DETAILED DESCRIPTION OF THE INVENTION
In one of its aspects, the present invention entails 1-(3-methoxybenzyl)-3-substituted thiourea compounds of the formula:
wherein R is selected from the group consisting of C
1
-C
20
linear or branched alkyl; C
5
-C
7
cycloalkyl; alkoxy-substituted C
5
-C
7
cycloalkyl; hydroxy-substituted C
5
-C
7
cycloalkyl; C
6
-C
7
aryl; hydroxy-substituted C
6
-C
7
aryl; and alkoxy-substituted C
6
-C
7
aryl. In a particularly preferred embodiment, the substituted aryl moiety is a 3-hydroxy-substituted or 3-alkoxy-substituted aryl compound.
In another of its aspects, the present invention entails a lipid composition with enhanced oxidative stability comprising from about 95 wt. % to about 99.99 wt. % of a base lipid and from about 0.01 wt. % to about 5.0 wt. %, more preferably between about 0.05 wt. % and 2.0 wt. %, and still more preferably about 0.1 wt. % to about 1.0 wt. % of a 1-(3-methoxybenzyl)-3-substituted thiourea compound of the formula:
wherein R is selected from the group consisting of C
1
-C
20
linear or
Abbott Thomas P.
Wohlman Alan
Barts Samuel
Feder Scott B.
Hastreiter Roberta L.
Lord, Bissell & Brook
Price Elvis O.
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