Process for the preparation of amine oxides

The present invention relates to an improved process for the preparation of high quality amine oxides from secondary and tertiary aliphatic amines by Mg—Al—O—t—Bu hydrotalcites using benzonitrile as an additive. More particularly, the present invention relates to an improved process for the preparation of amine oxides from secondary and tertiary aliphatic amines useful in the preparation of hair conditioners, shampoos, toothpaste, laundry detergent powder, fabric softeners, toilet soap bars, cosmetics and surfactants as well as in other applications as synthetic intermediates and excellent spin trapping reagents.

Amine N-oxides hold a key position in the chemistry of heterocycles as well as in biomedical area. The tertiary amine oxides are widely used in treatment of fabrics and preparation of hair conditioners, shampoos, toothpaste, laundry detergent powder, fabric softeners, toilet soap bars and cosmetics as well as in other applications. They were also used as stoichiometric oxidants in metal catalysed dihydroxylation and epoxidation reactions of olefins. On the other hand, the oxides derived from secondary amines, called nitrones are highly valuable synthetic intermediates and excellent spin trapping reagents. In particular nitrones are excellent 1,3 dipoles and have been utilized for the synthesis of various nitrogen containing biologically active compounds e.g. alkaloids and lactams.

Conventionally tertiary amine oxides are prepared by oxidation of respective tertiary amines with strong oxidising agent like aqueous hydrogen peroxide in a solvent such as water, lower alcohol, acetone or acetic acid. A dilute or preferably concentrated (30-90% by weight) hydrogen peroxide solution is added in stoichiometric or greater amount to an aqueous solution containing the tertiary amine to obtain amine oxide, (U.S. Pat No. 3,215, 741). The drawback is that the reaction transforms into a gel resembling a thick paste long before completion of reaction, which retards further reaction. The yields are only 30-40% by weight of amine oxide. Later several methods such as incorporation of catalyst and/chelating agent have been developed to in order to increase the quality and yields of the product.

In case of secondary amines, the classical methods involve the condensation of N-monosubstituted hydroxylamines with carbonyl compounds or the direct oxidation of N,N-disubstituted hydroxylamines. Later direct oxidation of secondary amines using several oxidising systems such as R 2 C(μ—O 2 ), Na 2 WO 4 —H 2 O 2 , SeO 2 , TPAP-NMO and UHP-M (M═Mo, W), MTO—H 2 O 2 have been developed to accomplish nitrones under homogenous conditions. The drawback in all the above cases is the difficulty in recovering the homogeneous catalyst/reagents from the reaction mixture.

Reference is made to a U.S. Pat. No. 3,283,007 wherein the oxidation of tertiary amines using diethelene trianine penta/tetra acetic acid as chelating agent and sometimes contaminated with heavy metals is recommended to improve the yield. The hydrogen peroxide solution employed has concentration of at least 30-75% by weight. The disadvantages of this process are high reaction temperatures ranging between 40-100° C., longer reaction periods, and lower yields of amine oxides.

Reference is made to U.S. Pat. No. 3,424,780, wherein high yields of tertiary amine oxides are achieved by carrying the oxidation of tertiary amine with 30-70% by weight of aqueous hydrogen peroxide using 0.01 to 2% weight of carbondioxide, in presence of a chelating agent, tetra acetylene diamine, a salt thereof, polyphosphates, stannates, a hydroxy carboxylic acid salts or the salt of poly carboxylic acid. The disadvantages of this process are longer reaction periods and the amine oxide formed is intensively coloured when carbon dioxide atmosphere is used to speed up the reaction and this method necessitates injecting a gas which requires handling facilities. Another disadvantage is more than 30% by weight of hydrogen peroxide is not environmentally friendly.

Reference is made to another U.S. Pat. No. 4,889,954 wherein the tertiary amines are reacted in high yields to give the corresponding amine oxides with a low content of nitrosamine, the oxidation of tertiary amine being carried out in the presence of a dialkyl carboxylic acid ester as catalyst and if appropriate, ascorbic acid as a co-catalyst using 45-70% by weight of hydrogen peroxide. The drawbacks in the above process are the requirement of frequent addition of water to avoid gel formation, high reaction temperatures, longer reaction periods and difficulty in separation of the catalyst from the reaction mixture.

Reference is made to another U.S. Pat. No. 4,565,891 wherein octacyano molybdate or iron salts are used as catalysts and molecular oxygen for oxidation of tertiary amines at high pressures and temperatures. The main drawback of this process is the need of very high temperature of 90-130° C. and low yields of amine oxide reporting 11-52% of conversion.

Reference is made to a U.S. Pat. No. 5,130,488 wherein the solid amine oxide can be prepared by reacting a tertiary amine with hydrogen peroxide using carbon dioxide in presence of acetate and cooling to precipitate the product. This process is superior to previously known methods of preparing amine oxides. However, its use can sometimes lead to cleavage of the solvents, plating on the walls of the vessel used for the precipitation, contamination of the product with residual peroxide, and or discoloration of the product.

Reference is made to a publication by Walter W. Zajac et al., J. Org. Chem.; 53, 5856, 1988 wherein the oxidation of secondary and tertiary amines using 2-sulfonyloxyaziridines (Davis Reagents) were reported. The drawback of the above process is, the reagent was used in stoichiometric amounts.

Reference is made to a publication by Shun-Ichi Murahashi et al., J. Org. Chem.; 55, 1736, 1990 wherein the sodium tungstate was used as catalyst for the oxidation of secondary amines. The drawback is difficulty in recovery of the catalyst from homogeneous conditions.

Reference is made to publication by Murraay et al., J. Org. Chem.; 61, 8099, 1996 wherein methyltrioxorhenium was used as a catalyst in oxidation of secondary amines. The drawback is the difficulty in recovery of the catalyst.

Reference is made to publication by Choudary et al., Chem. Commun.; 2001, 1736 wherein tungstate-exchanged Mg—Al—LDH was used as a catalyst in oxidation of tertiary amines. The time taken for the reaction is 3-4 h.

The main object of the present invention is to provide an eco-friendly and simple process for N-oxidation of secondary and tertiary amines using layered double hydroxides exchanged with anion of alkoxides as a catalyst which is cheaper, non-corrosive and recyclable catalyst utilising only lower percentage of hydrogen peroxide at moderate temperatures to give high yields of product.

Another object of the present invention is to provide an improved process for the preparation of tertiary amine oxides and secondary amine oxides (nitrones), widely used in detergents, shampoos, fabric softers and biomedical area.

Another object of the present invention is the use of non-corrosive and low cost heterogeneous catalysts i.e. layered double hydroxides exchanged with anion of tert-butoxide, isopropoxide, ethoxide and methoxide.

The present invention describes a recyclable heterogeneous catalyst, i.e. layered double hydroxides exchanged with anion of tert-butoxide, isopropoxide, ethoxide or methoxide that catalyses the oxidation of secondary and tertiary amines in presence of an additive selected from benzonitrile, propionitrile, acetonitrile, isobutyronirtile, benzamide, isobutyramide. The advantages such as low cost of the catalyst, reusability for several times and its ability to oxidise the amines at 10-65° C. in a shorter period make the present invention as a promising candidate for a clean and efficient industrial route to amine oxide preparation.

Accordingly the present invention provides a process for the preparation of amine oxide which comprises reacting a tertiary or a secondary amine with hydrogen peroxide as an oxidant in presence of a recyclable heterogeneous catalyst comprising a layered double hydroxide exchanged with an anion selected from the group containing tert-butoxide, ethoxide, isopropoxide and methoxide in the presence of an additive selected from the group consisting of benzonitrile, propionitrile, isobutyronitrile, benzamide and isobutyramide, in an organic solvent, and separating the product and recovering the additive.

In one embodiment of the invention, the reaction is carried out at a temperature in the range of 10-65° C. for a period of 0.5-5 hours under continuous stirring and the product is separated by filtration and subsequent evaporation of the solvent.

In a further embodiment of the invention, the layered double hydroxides exchanged with said anion is of the formula I: [M II (1−x) M III X (OH) 2 ][M n ] x/2 .zH 2 O, derived from LDH having formula II [M II (1−x) M III X (OH) 2 ][A n ] x/2 .zH 2 O, wherein M n− is an anion of tert-butoxide, isopropoxide, ethoxide and methoxide, An is an interstitial anion selected from nitrate, chloride and carbonate, M II is a divalent cation selected from Mg 2+ , Mn2+, Fe 2+ , V 2+ , Co 2+ , Ni 2+ , Cu 2+ , Zn 2+ Pd 2+ , and Ca 2+ , and M III is a trivalent ion selected from group consisting of Al 3+ , Cr 3+ , V 3+ , Mn 3+, Fe3+, Co 3+ , Ni 3+ , Rh3+, Ru 3+ , Ga 3+ and La 3+ .

In another embodiment of the invention, the tertiary amine is of the general formula R 1 R 2 NR 3 wherein R 1 , R 2 and R 3 are the same or different and are straight-chain or branched chain groups selected from alkyl, alkenyl and aralkyls having C 1 -C 24 carbons, and preferably are selected from imidazolines pyridines such as dimethyl decyl amine, dimethyl docyl amine and dimethylbenzylamine; N-substituted piperazines, and N-substituted morpholines such as N-substituted morpholine is N-methylmorpholine.

In another embodiment of the invention, the secondary amine is of the general formula R 1 R 2 NH wherein R 1 and R 2 are the same or different and are straight-chain or branched chain groups selected from alkyl, alkenyl and aralkyls having Cl-C 24 carbons, and cyclic amines.

In another embodiment of the invention, the secondary amine is selected from dibutyl amine, dibenzyl amine, N-benzyl phenethylamine, N-phenyl benzylamine, piperidine and 1,2,3,4 tetrahydro isoquinoline.

In another embodiment of the invention, 30% by weight of aqueous hydrogen peroxide is added slowly in a controlled manner during the period specified.

In another embodiment of the invention, the catalyst is 6-14% by weight of alkoxides selected from tert-butoxide, ethoxide, isopropoxide and methoxide.

In another embodiment of the invention, the reaction is effected at a temperature in the range of 10 to 65° C. for 1-6 hours.

In another embodiment of the invention, the organic solvent is selected from methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol and isobutyl alcohol.

In another embodiment of the invention, the amount of hydrogen peroxide used ranges between 2 to 6 moles per mole of secondary or tertiary amine.

In another embodiment of the invention, the amount of additive used is mole per mole of amine.

The present invention provides an improved process for the preparation of amine oxides of a very high quality which comprises reacting tertiary and secondary amines with hydrogen peroxide as an oxidant in presence of a recyclable heterogeneous catalyst, layered double hydroxides exchanged with anion of alkoxides selected from tert-butoxide, ethoxide, isopropoxide, and methoxide as catalysts in the presence of an additive selected from benzonitrile, propionitrile, isobutyronirtile, benzamide, isobutyramide in an organic solvent at a temperature ranging between 10-65° C. for a period of 1-2 hours under continuous stirring and separating the product by simple filtration and subsequently evaporation of solvents by known methods and recovering the additive for reuse. The heterogeneous catalyst used is the layered double hydroxides exchanged with the anion selected from a group consisting of tert-butoxide, isopropoxide, ethoxide and methoxide having formula I: [M II (1−x) M III x (OH) 2 ][M n− ] x/2 .zH 2 O, which is derived from LDH having formula II [M II (1−x) M III x (OH) 2 ][A n− ] x/2 .zH 2 O where M n− is an anion of tert-butoxide, isopropoxide, ethoxide and methoxide, A n− is interstitial anion, selected from nitrate, chloride, carbonate and M II is a divalent cation selected from the group consisting of Mg 2+ , Mn2+, Fe 2+ , V 2+ , Co 2+ , Ni 2+ , Cu 2+ , Zn 2+ Pd 2+ , or Ca 2+ and M m is a trivalent ion selected from the group consisting of Al 3+ , Cr 3+ , V 3+ , Mn3+, Fe 3+ , Co 3+ , Ni 3+ , Rh 3+, Ru 3+ , Ga 3+ or La 3+ . The tertiary amines used are the formula R 1 R 2 NR 3 wherein R 1 , R 2 and R 3 , which may be the same or different, and are the straight-chain or branched-chain groups selected from alkyl, alkenyl and aralkyls having C 1 -C 24 carbons selected from N,N- dimethyl decyl amine, N,N-dimethyl dodecyl amine, N,N-dimethylbenzylamine, triethylamine, tributylamine and cyclic amines selected from imidazolines pyrididines, N-substituted piperazines, N-substituted piperadines or N-substituted morpholines, e.g., N-methylmorpholine. The secondary amines used are having general formula R 1 R 2 NH wherein R 1 and R 2 may be the same or different and are the straight-chain or branched-chain groups selected from alkyl, alkenyl and aralkyls having C 1 -C 24 carbons, selected from dibutyl amine, dibenzyl amine, N-benzyl phenethylamine, N-phenyl benzylamine and cyclic amines selected from piperidine, 1,2,3,4, tetrahydro isoquinoline. The present invention aqueous hydrogen peroxide is added slowly in a controlled manner for a period ranges between 0-15 min. The catalyst introduced in the system is 6-14% by weight of anion of alkoxides selected from tert-butoxide, isopropoxide, ethoxide and methoxide. The organic solvents are preferably methonol, ethanol, isopropanol, 1-propanol, 1-butanol, 2-butanol and tert-butyl alcohol, acetonitrile, tetrahydrofuran, dichloromethane, dichloroethane.

The reaction is effected at a temperature in the range of 10 to 65° C. for 0.5-5 hours. The amount of hydrogen peroxide used is 2 to 6 moles per mole of amine. The amount of additive benzonitrile, propionitrile, acetonitrile, isobutyronirtile, benzamide or isobutyramide used is mole per mole of amine which can be recovered quantitatively and reused to make the process more economical. The novelty of the invention lies in the use of solid base catalyst for the first time for the N-oxidation of secondary and tertiary amines. The anion of alkoxides, intercalated in the layered double hydroxides, effectively catalyses the oxidation of amines to amine oxides. The filtrate-containing product was removed by decantation and the solid catalyst is recycled for several times by the addition of fresh substrates and solvent without the addition of fresh catalyst. The consistent activity for several cycles under moderate reaction conditions in shorter reaction times makes the process economical and possible for commercial realisation.

Scheme 1. The plausible reaction mechanism for the N-oxidation of amines catalysed by Mg—Al—O—t—Bu hydrotalcite using aqueous hydrogen peroxide.

The plausible reaction mechanism for the oxidation of tertiary and secondary amines is shown in Scheme 1. Initially hydrogen peroxide reacts with basic tert-butoxide of Mg—Al—O—t—Bu hydrotalcite (I) catalyst to form HOO − species (11), which attacks the nirtile (IV) to generate a peroxycarboximidic acid (III) as an active intermediate oxidant. The active peroxycarboximidic acid further delivers electrophilic oxygen to nitrogen atom of tert-amine (VI) forming desired N-oxides (VII) and amide as by product (V). The secondary amine (IX) undergoes nucleophilic reaction with peroxycarboximidic acid (III) species to give hydroxylamine (X). Further oxidation of hydroxylamine (X) followed by dehydration gives nitrone (XI).

The following examples are given by way of illustration of the present invention and therefore should not be construed to limit the scope of the present invention.