CA1244031A - Process for preparing nitroxyls of sterically hindered amines - Google Patents
Process for preparing nitroxyls of sterically hindered aminesInfo
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- CA1244031A CA1244031A CA000476966A CA476966A CA1244031A CA 1244031 A CA1244031 A CA 1244031A CA 000476966 A CA000476966 A CA 000476966A CA 476966 A CA476966 A CA 476966A CA 1244031 A CA1244031 A CA 1244031A
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- hydroperoxide
- metal
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- amine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/92—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with a hetero atom directly attached to the ring nitrogen atom
- C07D211/94—Oxygen atom, e.g. piperidine N-oxide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/06—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members
- C07D241/08—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
PROCESS FOR PREPARING NITROXYLS OF STERICALLY HINDERED AMINES
Abstract of the Disclosure Nitroxyls of the formula
Abstract of the Disclosure Nitroxyls of the formula
Description
Case 3-14806/=/CGC 1075 PROCESS FOR PREPARING NITROXYLS OF STERICALLY HINDERED AMINES
Nitroxyls (also called N-oxyls or nitroxides) are free radicals having an unpaired electron. They are obtainable by oxidation of secondary amines and are stable compounds, if the two carbon atoms linked to the nitrogen do not bear a hydrogen atom so that they are tertiary carbon atoms. For their preparation from secondary amines ozone may be used as oxidant tS.D. Ra~umovskii et al., Chem. Abstracts _ (1969), 95987). More frequently used as antioxidants are per-carboxylic acids (G. Chapelet-Letourneux et al., Bull. Soc. Chem.
1965, 3283) or aqueous H202 in the presence of pertungstate ion [O.L. Lebedev et al., Proc. Acad. Sci USSR, Chem. Sect., 140, (1962);
O.L. Lebedev, S.N. ICazarnovskii, Chem. Abstr. S6 (1962), 15479].
The last method is very suitable Eor the oxidation of water-soluble secondary amines. However, if the amine is only sparingly soluble in water, the reaction becomes very slow and the yields are low.
For those amines the oxidation with peracids in organic solvents is preferred, Eor example with m-chloroperbenzoic acid. Such peracids, however, are expensive materials and may cause trouble by salt formation with the amine.
A neutral oxidant which can be used in organic solvents are organic hydroperoxides, such as tert-butylhydroperoxide. O.W. Maender and E.G. Janzen [J. Org. Chem. 34 (1969), 4082] have investigated the use of tert-butylhydroperoxide for the oxidation of secondary trityl amines, but could not obtain the corresponding nitroxyles. In US
patent 3,634,346 some years later it was shown that cyclic secondary d~
amines can be oxidized with organic hydroperoxides in the presence of metal salt catalysts to yield the corresponding lactames. Thus, from the literature it was to conclude that secondary amines cannot be transformed to the nitroxyls by oxidation with organic hydro-peroxides.
Therefore it was surprising to find that by reaction of sterically hindered cyclic secondary amines with organic hydroperoxides in the presence of certain metal compounds as catalysts the corresponding nitroxyls can be obtained in high yield and purity.
Generically the instant invention is a process for the preparation of a nitroxyl of the formula I
~ T ~
E27 ~ E3 (I) O~
where ~he nitrogen atom is flanked by two quaternary carbon atoms, where El, E2, E3 and E4 are independently an organic radical.
and T is a dlvalent gro~lp required to form a cyclic 5- or 6-membered ring which comprises reacting an amine of the formula II
1 / ~ 4 (II) where El, E2, E3, E4 and T have the meanings given above, dissolved in an inert organic solvent, with an organic hydroperoxide in the presence of catalytic amounts of a metal carbonyl, a metal oxide, a metal acetylacetonate or a metal alkoxide where the metal is selected from groups IVb, Vb, VIb, VIIb and VIII
of the periodic table, at a temperature of 0 to 200C, preferably -~%~
50 to 150C, with the mole ratio of hydroperoxide to amine being 50:1 to 1:10, preferably 10:1 to 1:1.
More specifically, the instant invention is a process for the preparation of a nitroxyl of the formula I, wherein El and E3 are independently alkyl of 1 to 5 carbon atoms or phenyl, E2 and E4 are independently alkyl of 1 to 5 carbon atoms, or El and E2 together or E3 and E4 together or both El and E2 together and E3 and E4 together are tetramethylene or pentamethylene, and T is a divalent group required to form a cyclic 5- or 6-membered ring.
Preferably El, E2, E3 and E4 are each methyl.
The nature of T is not critical to the instant process with the understanding that T remains inert, that is T remains chemically tmchanged, to hydroperoxide attack or to subsequent catalytic reduction.
The amines which can be oxidized according to the invention contain a nitrogen atom which is substituted by two tertiary alkyl groups.
Preferred compounds are cyclic amines having the two methylene adjacent to the ring nitrogen fully substituted by alkyl groups.
By way of illustration, 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl, 4-benzoyloxy-2,2,6,6-tetramethylpiperidin-1-oxyl, 3-carbamoyl-
Nitroxyls (also called N-oxyls or nitroxides) are free radicals having an unpaired electron. They are obtainable by oxidation of secondary amines and are stable compounds, if the two carbon atoms linked to the nitrogen do not bear a hydrogen atom so that they are tertiary carbon atoms. For their preparation from secondary amines ozone may be used as oxidant tS.D. Ra~umovskii et al., Chem. Abstracts _ (1969), 95987). More frequently used as antioxidants are per-carboxylic acids (G. Chapelet-Letourneux et al., Bull. Soc. Chem.
1965, 3283) or aqueous H202 in the presence of pertungstate ion [O.L. Lebedev et al., Proc. Acad. Sci USSR, Chem. Sect., 140, (1962);
O.L. Lebedev, S.N. ICazarnovskii, Chem. Abstr. S6 (1962), 15479].
The last method is very suitable Eor the oxidation of water-soluble secondary amines. However, if the amine is only sparingly soluble in water, the reaction becomes very slow and the yields are low.
For those amines the oxidation with peracids in organic solvents is preferred, Eor example with m-chloroperbenzoic acid. Such peracids, however, are expensive materials and may cause trouble by salt formation with the amine.
A neutral oxidant which can be used in organic solvents are organic hydroperoxides, such as tert-butylhydroperoxide. O.W. Maender and E.G. Janzen [J. Org. Chem. 34 (1969), 4082] have investigated the use of tert-butylhydroperoxide for the oxidation of secondary trityl amines, but could not obtain the corresponding nitroxyles. In US
patent 3,634,346 some years later it was shown that cyclic secondary d~
amines can be oxidized with organic hydroperoxides in the presence of metal salt catalysts to yield the corresponding lactames. Thus, from the literature it was to conclude that secondary amines cannot be transformed to the nitroxyls by oxidation with organic hydro-peroxides.
Therefore it was surprising to find that by reaction of sterically hindered cyclic secondary amines with organic hydroperoxides in the presence of certain metal compounds as catalysts the corresponding nitroxyls can be obtained in high yield and purity.
Generically the instant invention is a process for the preparation of a nitroxyl of the formula I
~ T ~
E27 ~ E3 (I) O~
where ~he nitrogen atom is flanked by two quaternary carbon atoms, where El, E2, E3 and E4 are independently an organic radical.
and T is a dlvalent gro~lp required to form a cyclic 5- or 6-membered ring which comprises reacting an amine of the formula II
1 / ~ 4 (II) where El, E2, E3, E4 and T have the meanings given above, dissolved in an inert organic solvent, with an organic hydroperoxide in the presence of catalytic amounts of a metal carbonyl, a metal oxide, a metal acetylacetonate or a metal alkoxide where the metal is selected from groups IVb, Vb, VIb, VIIb and VIII
of the periodic table, at a temperature of 0 to 200C, preferably -~%~
50 to 150C, with the mole ratio of hydroperoxide to amine being 50:1 to 1:10, preferably 10:1 to 1:1.
More specifically, the instant invention is a process for the preparation of a nitroxyl of the formula I, wherein El and E3 are independently alkyl of 1 to 5 carbon atoms or phenyl, E2 and E4 are independently alkyl of 1 to 5 carbon atoms, or El and E2 together or E3 and E4 together or both El and E2 together and E3 and E4 together are tetramethylene or pentamethylene, and T is a divalent group required to form a cyclic 5- or 6-membered ring.
Preferably El, E2, E3 and E4 are each methyl.
The nature of T is not critical to the instant process with the understanding that T remains inert, that is T remains chemically tmchanged, to hydroperoxide attack or to subsequent catalytic reduction.
The amines which can be oxidized according to the invention contain a nitrogen atom which is substituted by two tertiary alkyl groups.
Preferred compounds are cyclic amines having the two methylene adjacent to the ring nitrogen fully substituted by alkyl groups.
By way of illustration, 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl, 4-benzoyloxy-2,2,6,6-tetramethylpiperidin-1-oxyl, 3-carbamoyl-
2,2,5,5-tetramethyl-pyrrolidin-1-oxyl, N-(l-oxyl-2,2,6,6-tetra-methylpiperidin-4-yl)-2-caprolactam, 3-oxyl-2,2,4,4-tetrctmethyl-7-oxa-3,20-diazaspiro[5.1.11.2]heneicosan-21-one, 4-aza-3,3-dimethyl-4-oxyl-1-oxaspiro[4.5]decane or 2,4,4-trimethyl-2-phenyloxazolidin-
3-oxyl can be prepared from the corresponding secondary cyclic amine.
The alkyl hydroperoxides which may be used in the process of this invention are tertiary-alkyl hydroperoxide, i.e., an alkane having a hydroperoxy group substituted on a tertiary carbon atom, or aralkyl hydroperoxides, wherein the hydroperoxy group is attached to the ~-carbon of an aralkyl compound.
Suitable hydroperoxides are tert-butyl hydroperoxide, tert-amyl hydroperoxide, tert-hexyl hydroperoxide, tert-octyl hydroperoxide, ethylbenzene hydroperoxide, tetralin hydroperoxide or cumene (= isopropylbenzene) hydroperoxide.
Preferred hydroperoxides are tert-butyl hydroperoxide, tert-amyl hydroperoxide, ethylbenæene hydroperoxide~ and cumene hydroperoxide.
Especially preferred are tert-butyl hydroperoxide and cumene hydro-peroxide.
The reaction is conducted in the liquid phase in solvents which are substantially inert to the reactants and the products produced theref rom .
Illustrative suitable solvents are esters, such as butyl acetate;
ketones, such as acetone; ethers such as dibutyl ether, dioxane or tetrahydrofuran; chlorinated solvents, such as methylene chloride, 1,2-dichloroethane or dichlorobenzene; alkanes, such as hexane, decane; aromatic solvents, such as benzene, toluene, xylene, isopropylbenzene (cumene).
In most instances the solvent is used in amounts up to 20 moles of solvent per mole of hydroperoxide.
In the preferred procedure the amine, the catalyst and the solvent are charged into a reaction vessel and the reaction mixture is maintained with agitation at the reaction temperature during the -~CL~ ~,3~
addition of peroxide. In another modification, reaction is efEected continuously by contacting the amine and the hydroperoxide in a solvent containing the catalyst.
Suitable reaction temperatures vary from 0 to 200C, but preferably from 50 to 150C.
The catalysts are selected from the group consisting of the metal carbonyls, the metal oxides, the metal acetylacetonates and the metal alkoxides where the metal is selected from the groupsIVb,Vb,VIb, VIIb and VIII of the periodic table. Examples of effective catalysts include vanadyl acetylacetonate, cobalt carbonyl, titanium (IV) isopropoxide, molybdenum hexacarbonyl, molybdenum trioxide and the like. Especially preferred are molybdenum and titanium catalysts.
The amount of metal ion catalyst whicll is added to the reaction mixture is not narrowly critical and need only be added in amounts effective to initiate the reaction. An additional advantage of the instant process is that large amounts of catalyst are not required.
The preferred range of cata]yst is from 0.001 mole percent or lower to about 0.1 mole percent or higher based upon the hydroperoxide employed. Any amount can be used as long as it is catalytically effective. There is no limit to the upper range other than economic considerations.
At the end of the reaction, the product mixture is separated and the desired nitroxyl products are recovered by conventional methods.
Alternatively, the reaction mixture containing the desired nitroxyl compound may be used directly for the preparation of the corresponding hydroxylamine by reductive treatment of the reaction solution. The procedure required for this reduction may be a catalytic hydrogenation in the presence of a noble metal or nickel catalyst or a chemical reduction using zinc,boraneorotherclassical reducing agents.
Thus, another aspect of the instant invention is a process for the preparation of a hydroxylamine of the formula III
T ~
/ y ~ 4 (III) OH
wherein El, E2, E3, E4 and T are as defined above, by reacting a compound of formula II as described before and subsequent reductive treatment of the reaction solution without isolation of the intermediate of formula I.
The compounds of formula I are orange to red coloured compounds and can be used as spin-labels and spin-probes in ESR spectroscopy. They can further be used as polymerization inhibitors for unsaturated compounds or as stabilizers for organic polymers against their thermal and photochemical degradat;on.
The compounds oE Eormula III are colourless compounds and can be used as antioxidants for organic materials. Exc~lples of compounds oE
formula III are 1,4-dihydroxy-2,2,6,6-tetramethylpiperidine,
The alkyl hydroperoxides which may be used in the process of this invention are tertiary-alkyl hydroperoxide, i.e., an alkane having a hydroperoxy group substituted on a tertiary carbon atom, or aralkyl hydroperoxides, wherein the hydroperoxy group is attached to the ~-carbon of an aralkyl compound.
Suitable hydroperoxides are tert-butyl hydroperoxide, tert-amyl hydroperoxide, tert-hexyl hydroperoxide, tert-octyl hydroperoxide, ethylbenzene hydroperoxide, tetralin hydroperoxide or cumene (= isopropylbenzene) hydroperoxide.
Preferred hydroperoxides are tert-butyl hydroperoxide, tert-amyl hydroperoxide, ethylbenæene hydroperoxide~ and cumene hydroperoxide.
Especially preferred are tert-butyl hydroperoxide and cumene hydro-peroxide.
The reaction is conducted in the liquid phase in solvents which are substantially inert to the reactants and the products produced theref rom .
Illustrative suitable solvents are esters, such as butyl acetate;
ketones, such as acetone; ethers such as dibutyl ether, dioxane or tetrahydrofuran; chlorinated solvents, such as methylene chloride, 1,2-dichloroethane or dichlorobenzene; alkanes, such as hexane, decane; aromatic solvents, such as benzene, toluene, xylene, isopropylbenzene (cumene).
In most instances the solvent is used in amounts up to 20 moles of solvent per mole of hydroperoxide.
In the preferred procedure the amine, the catalyst and the solvent are charged into a reaction vessel and the reaction mixture is maintained with agitation at the reaction temperature during the -~CL~ ~,3~
addition of peroxide. In another modification, reaction is efEected continuously by contacting the amine and the hydroperoxide in a solvent containing the catalyst.
Suitable reaction temperatures vary from 0 to 200C, but preferably from 50 to 150C.
The catalysts are selected from the group consisting of the metal carbonyls, the metal oxides, the metal acetylacetonates and the metal alkoxides where the metal is selected from the groupsIVb,Vb,VIb, VIIb and VIII of the periodic table. Examples of effective catalysts include vanadyl acetylacetonate, cobalt carbonyl, titanium (IV) isopropoxide, molybdenum hexacarbonyl, molybdenum trioxide and the like. Especially preferred are molybdenum and titanium catalysts.
The amount of metal ion catalyst whicll is added to the reaction mixture is not narrowly critical and need only be added in amounts effective to initiate the reaction. An additional advantage of the instant process is that large amounts of catalyst are not required.
The preferred range of cata]yst is from 0.001 mole percent or lower to about 0.1 mole percent or higher based upon the hydroperoxide employed. Any amount can be used as long as it is catalytically effective. There is no limit to the upper range other than economic considerations.
At the end of the reaction, the product mixture is separated and the desired nitroxyl products are recovered by conventional methods.
Alternatively, the reaction mixture containing the desired nitroxyl compound may be used directly for the preparation of the corresponding hydroxylamine by reductive treatment of the reaction solution. The procedure required for this reduction may be a catalytic hydrogenation in the presence of a noble metal or nickel catalyst or a chemical reduction using zinc,boraneorotherclassical reducing agents.
Thus, another aspect of the instant invention is a process for the preparation of a hydroxylamine of the formula III
T ~
/ y ~ 4 (III) OH
wherein El, E2, E3, E4 and T are as defined above, by reacting a compound of formula II as described before and subsequent reductive treatment of the reaction solution without isolation of the intermediate of formula I.
The compounds of formula I are orange to red coloured compounds and can be used as spin-labels and spin-probes in ESR spectroscopy. They can further be used as polymerization inhibitors for unsaturated compounds or as stabilizers for organic polymers against their thermal and photochemical degradat;on.
The compounds oE Eormula III are colourless compounds and can be used as antioxidants for organic materials. Exc~lples of compounds oE
formula III are 1,4-dihydroxy-2,2,6,6-tetramethylpiperidine,
4-benzoyloxy-1-hydroxy-2,2,6,6-tetramethylpiperidine, di(l-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl) sebacate or N-(l-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl)-F~caprolactam.
The following examples are presented for the purpose of illustration only and are not to be construed to limit the nature or scope of the instant invention in any manner whatsoever.
xample 1: Preparation of 4-hydroxy-2,2,6,6-tetramethylpiperidin-l-oxyl.
___ A reactor is charged with 50 ml of reagent-grade 1,2-dichloroethane, 8.5 g (0.054 mole) oE 2,2,6,6~tetramethylpiperidin-4-ol and 0.10 g of molybdenum hexacarbonyl, Mo(C0)6. The mixture is brought to reflux to give a clear solution. A dropping funnel is charged with 27 ml of 4M tert-butyl hydroperoxide in 1,2-dichloroethane and this solution is then added dropwise into the reactor, at a rate sufficient to maintain a gentle reflux without external heat.
The addition requires about 0.5 hour after which heat is applied for 4 hours. At this point gas chromatography (~C) showed ~ 2% of unreacted amine. The reaction mixture is cooled, washed with 5 % aqueous sodium sulfite. The aqueous phase is extracted with 50 ml of chloroform and the combined organic phases are dried over anhydrous magnesium sulfate. After evaporation of the solvents, the residue is crystallized from hexane, yielding 8.0 g (86 % yield) of orange crystals, m.p. 69-71 (lit. 71C).
(H. Lemaire, et al, ~ull. Soc. Chim. France 1968, 886).
Example 2: When an equivalent amount of molybdenum (VI) oxide, -MoO3, is substituted for the molybdenum hexacarbonyl catalyst using the method of Example 1, after two hours reaction time more than 98 % of the 2,2,6,6-tetramethylpiperidin-4-ol is converted to the corresponding N-oxyl compound as seen by gas chromatography.
3~
_xample 3: When an equivalent amount of vanadyl acetylacetonate is substituted for the molybdenum hexacarbonyl catalyst using the method of Example 1, some insoluble material is obtained. The reac-tion is slower and after 2 hours only 31 % of the amine is converted to the N-oxyl group as seen by gas chromatography.
xample 4: Preparation of N-(l-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)-~- caprolactam A sample of 25.2 g (0.1 mole) of N-(2,2,6,6-tetramethylpiperidin-4-yl)-~- caprolactam is refluxed for 2 hours with 50 ml of 4M
tert-butylhydroperoxide in the presence of 0.2 g of molybdenum hexacarbonyl, Mo(C0)6 as described in Example 1, to provide 26.6 g of red solid (99% crude yield). Crystallization from hexane gives orange crystals, m.p. 152-159C.
Analysis:
Calcd. for C15H27N202: C, 67.3; H, 10.1; N, 10.4%
Found: C, 66.9; H, 9.9; N, 10.2%
Example 5: When the molebdenum hexacarbonyl catalyst used in Example 4 is replaced by an equivalent amount oE titanlum tetra-isopropoxide with a molar ratio of Ti(IV) to amine of 0.04, gas chromatography shows a 95 % conversion of amine to the product of Example 4 after 5 hours.
xample 6: Preparation of 4-benzoyloxy-2,2,6,6-tetramethylpiperidin-l-oxyl When 13.1 g (0.05 mole) of (2,2,6,6-tetramethylpiperidin-4-yl) benzoate is oxidized as described by the method of Example 1, 9.5 g (69~ yield) of orange crystals are isolated: m.p. 104-106C (from methanol) (lit. m.p. 105C).
Lf~ ~3~, _ g _ [V.A. Golubev, et al, Izv. Akad. Nauk. SSSR, Ser. Khim. 1965, 1927 = CA, 64, 11164e (1966)].
xample 7: Preparation of di-(l-hydroxyl-2,2,6,6-tetramethyl-piperidin-4-yl) sebacate A solution containing 15.0 g (31.2 mmole) of di-(2,2,6,6-tetramethyl-piperidin-4-yl) sebacate and 0.2 g molybdenum hexacarbonyl, Mo(CO)6, (0.76 mmole) in 100 ml 1,2-dichloroethane i5 brought to reflux.
Tert-butyl hydroperoxide (31.5 ml 4M solution in 1,2-dichloroethane, 126 mmole) is added within 15 minutes and the solution is refluxed for 2.5 hours. The solution is cooled to room temperature, washed twice with 100 ml water, and the organic phase transferred to a hydrogenation flask. Catalytic hydrogenation is carried out at room temperature and with a hydrogen pressure of 40 psi (2.8 kg~cm2) to yield the hydroxylamine. The palladium/charcoal catalyst is removed by filtration and the solvent is evaporated. The solid is then recrystalli~ed from ethanol-water (4:1, 250 ml), under a blanket of nitrogen to prevent oxidation of the product. A colorless solid is obtained tl3.6 g, 85 % yield) m.p. 129-134C (lit.m.p. 101C).
[E,F. Litvin, et al, Zh. Org. ~him. 6, 2365 (1970) = CA, 74, 64180u (1971].
xample 8: Preparation of 3-oxyl-2,2,4,4-tetramethyl-7-oxa-3,20-diazaspiro[5.1.11.2]heneicosan-21-one A sample of 18.3 g (0.050 mole) of 2,2,4,4-tetramethyl-7-oxa-3,20-diazaspiro[5.1.11.2]heneicosan-21-one in 100 ml 1,2-dichloroethane is oxidized with 25 ml 4.0 M tert-butylhydroperoxide in the same solvent, using 0.3 g molybdenum hexacarbonyl, Mo(CO)6, catalyst.
After refluxing for 3 hours, thin layer chromatography TLC shows 95 ~ conversion.
- \
Example 9: Preparat;on of 1,1'-ethylenebis-(4-hydroxy-3,3,5,5-tetramethylpiperazin-2-one) Oxidation of 16.9 g (0.05 mole) of 1,1'-ethylenebis-(3,3,5,5-tetra-methylpiperazin-2-one) gives a product, which is hydrogenated without isolation as in Example 7. The hydrogenation catalyst is removed by filtration and the solvent evaporated, giving 15.1 g of light pink product (82% yield) m.p. 193C. Recrystallization from ethyl acetate-methanol gives the title compound as a pure white solid, m.p. 200~C.
Analysis:
Calcd for C18H34N404: C, 58.4; H, 9.3; N, 15.1.
Found: C, 58.5; H, 9.3; N, 15Ø
NMR (DMSO-d6): 1.21 ts, 12H, 4 CH3 axial); 1.43 (s, 12H, 4CH3 equatorial); 3.20 and 3.50 (s, 8H, CH2N); 4.60 (broad s, 2H, 011).
Example 10: Preparation oE 4-benzoyloxy-1-hydroxy-2,2,6,6-tetra-_thylpiperidine A solution containing 26.2 g (0.1 mole) of (2,2,6,6-tetramethyl-piperidin-4-yl) benzoate and 0.2 g molybdenum hexacarbonyl, Mo(CO)6, in 20 ml toluene is warmed to 60C. Cumene hydroperoxide (38.1 g of 80% solution, c.a. 0.2 mole) is added over a 45 minute period, giving a slightly exothermic reaction. Then the red solution is heated for another 30 minutes at 65 and transferred to a hydro-genation bottle.
The material is hydrogenated in the presence of 0.6 g 5% palladium-on-charcoal at 50 psi (3.5 kg/cm ) for 3 hours. The catalyst is then removed by filtration and washed with 100 ml of chloroform.
2~
The filtrate is stripped of chloroform, and 100 ml of hot hexane is added. The mixture is cooled and 20.0 g (72~ yield) of white precipitate is collected: m.p. 145-149C. (lit. 135-146C; see reference in Example 6).
Example 11: Preparation of 4-aza-3,3-dimethyl-4-oxyl-1-oxaspiro-~4.5]decane A solution of 32.1 g (0.19 mole)of 4-a~a-3,3-dimethyl-1-oxaspiro-[4.5]decane and 0.7 g of molybdenum hexacarbonyl, Mo(C0)6, in 75 ml of toluene is heated to 90DC and 100 ml of 4M tert-butylhydro-peroxide in toluene is added over a 30-minute period. The solution is heated for another 45 minutes at 90C to give the corresponding 4-oxyl compound in situ. The starting substituted oxazolidine is prepared by the method given in J. ~m. Chem. Soc. 66, 1738 (1944).
The 4-oxyl compound is described in J. Am. Chem. Soc. 89, 3054 (1967).
Example 12: Preparation oE 2,2,4-trimethyl-2-phenyl-3-oxyloxazolidine When using the procedure of Example ll, an equivalent amount of 2,4,4-trimethyl-2-phenyloxazolidine is substituted Eor the 4-aza-3,3-dimethyl-l-oxaspiro~4.5]decane, the above-named compound is prepared.
The following examples are presented for the purpose of illustration only and are not to be construed to limit the nature or scope of the instant invention in any manner whatsoever.
xample 1: Preparation of 4-hydroxy-2,2,6,6-tetramethylpiperidin-l-oxyl.
___ A reactor is charged with 50 ml of reagent-grade 1,2-dichloroethane, 8.5 g (0.054 mole) oE 2,2,6,6~tetramethylpiperidin-4-ol and 0.10 g of molybdenum hexacarbonyl, Mo(C0)6. The mixture is brought to reflux to give a clear solution. A dropping funnel is charged with 27 ml of 4M tert-butyl hydroperoxide in 1,2-dichloroethane and this solution is then added dropwise into the reactor, at a rate sufficient to maintain a gentle reflux without external heat.
The addition requires about 0.5 hour after which heat is applied for 4 hours. At this point gas chromatography (~C) showed ~ 2% of unreacted amine. The reaction mixture is cooled, washed with 5 % aqueous sodium sulfite. The aqueous phase is extracted with 50 ml of chloroform and the combined organic phases are dried over anhydrous magnesium sulfate. After evaporation of the solvents, the residue is crystallized from hexane, yielding 8.0 g (86 % yield) of orange crystals, m.p. 69-71 (lit. 71C).
(H. Lemaire, et al, ~ull. Soc. Chim. France 1968, 886).
Example 2: When an equivalent amount of molybdenum (VI) oxide, -MoO3, is substituted for the molybdenum hexacarbonyl catalyst using the method of Example 1, after two hours reaction time more than 98 % of the 2,2,6,6-tetramethylpiperidin-4-ol is converted to the corresponding N-oxyl compound as seen by gas chromatography.
3~
_xample 3: When an equivalent amount of vanadyl acetylacetonate is substituted for the molybdenum hexacarbonyl catalyst using the method of Example 1, some insoluble material is obtained. The reac-tion is slower and after 2 hours only 31 % of the amine is converted to the N-oxyl group as seen by gas chromatography.
xample 4: Preparation of N-(l-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)-~- caprolactam A sample of 25.2 g (0.1 mole) of N-(2,2,6,6-tetramethylpiperidin-4-yl)-~- caprolactam is refluxed for 2 hours with 50 ml of 4M
tert-butylhydroperoxide in the presence of 0.2 g of molybdenum hexacarbonyl, Mo(C0)6 as described in Example 1, to provide 26.6 g of red solid (99% crude yield). Crystallization from hexane gives orange crystals, m.p. 152-159C.
Analysis:
Calcd. for C15H27N202: C, 67.3; H, 10.1; N, 10.4%
Found: C, 66.9; H, 9.9; N, 10.2%
Example 5: When the molebdenum hexacarbonyl catalyst used in Example 4 is replaced by an equivalent amount oE titanlum tetra-isopropoxide with a molar ratio of Ti(IV) to amine of 0.04, gas chromatography shows a 95 % conversion of amine to the product of Example 4 after 5 hours.
xample 6: Preparation of 4-benzoyloxy-2,2,6,6-tetramethylpiperidin-l-oxyl When 13.1 g (0.05 mole) of (2,2,6,6-tetramethylpiperidin-4-yl) benzoate is oxidized as described by the method of Example 1, 9.5 g (69~ yield) of orange crystals are isolated: m.p. 104-106C (from methanol) (lit. m.p. 105C).
Lf~ ~3~, _ g _ [V.A. Golubev, et al, Izv. Akad. Nauk. SSSR, Ser. Khim. 1965, 1927 = CA, 64, 11164e (1966)].
xample 7: Preparation of di-(l-hydroxyl-2,2,6,6-tetramethyl-piperidin-4-yl) sebacate A solution containing 15.0 g (31.2 mmole) of di-(2,2,6,6-tetramethyl-piperidin-4-yl) sebacate and 0.2 g molybdenum hexacarbonyl, Mo(CO)6, (0.76 mmole) in 100 ml 1,2-dichloroethane i5 brought to reflux.
Tert-butyl hydroperoxide (31.5 ml 4M solution in 1,2-dichloroethane, 126 mmole) is added within 15 minutes and the solution is refluxed for 2.5 hours. The solution is cooled to room temperature, washed twice with 100 ml water, and the organic phase transferred to a hydrogenation flask. Catalytic hydrogenation is carried out at room temperature and with a hydrogen pressure of 40 psi (2.8 kg~cm2) to yield the hydroxylamine. The palladium/charcoal catalyst is removed by filtration and the solvent is evaporated. The solid is then recrystalli~ed from ethanol-water (4:1, 250 ml), under a blanket of nitrogen to prevent oxidation of the product. A colorless solid is obtained tl3.6 g, 85 % yield) m.p. 129-134C (lit.m.p. 101C).
[E,F. Litvin, et al, Zh. Org. ~him. 6, 2365 (1970) = CA, 74, 64180u (1971].
xample 8: Preparation of 3-oxyl-2,2,4,4-tetramethyl-7-oxa-3,20-diazaspiro[5.1.11.2]heneicosan-21-one A sample of 18.3 g (0.050 mole) of 2,2,4,4-tetramethyl-7-oxa-3,20-diazaspiro[5.1.11.2]heneicosan-21-one in 100 ml 1,2-dichloroethane is oxidized with 25 ml 4.0 M tert-butylhydroperoxide in the same solvent, using 0.3 g molybdenum hexacarbonyl, Mo(CO)6, catalyst.
After refluxing for 3 hours, thin layer chromatography TLC shows 95 ~ conversion.
- \
Example 9: Preparat;on of 1,1'-ethylenebis-(4-hydroxy-3,3,5,5-tetramethylpiperazin-2-one) Oxidation of 16.9 g (0.05 mole) of 1,1'-ethylenebis-(3,3,5,5-tetra-methylpiperazin-2-one) gives a product, which is hydrogenated without isolation as in Example 7. The hydrogenation catalyst is removed by filtration and the solvent evaporated, giving 15.1 g of light pink product (82% yield) m.p. 193C. Recrystallization from ethyl acetate-methanol gives the title compound as a pure white solid, m.p. 200~C.
Analysis:
Calcd for C18H34N404: C, 58.4; H, 9.3; N, 15.1.
Found: C, 58.5; H, 9.3; N, 15Ø
NMR (DMSO-d6): 1.21 ts, 12H, 4 CH3 axial); 1.43 (s, 12H, 4CH3 equatorial); 3.20 and 3.50 (s, 8H, CH2N); 4.60 (broad s, 2H, 011).
Example 10: Preparation oE 4-benzoyloxy-1-hydroxy-2,2,6,6-tetra-_thylpiperidine A solution containing 26.2 g (0.1 mole) of (2,2,6,6-tetramethyl-piperidin-4-yl) benzoate and 0.2 g molybdenum hexacarbonyl, Mo(CO)6, in 20 ml toluene is warmed to 60C. Cumene hydroperoxide (38.1 g of 80% solution, c.a. 0.2 mole) is added over a 45 minute period, giving a slightly exothermic reaction. Then the red solution is heated for another 30 minutes at 65 and transferred to a hydro-genation bottle.
The material is hydrogenated in the presence of 0.6 g 5% palladium-on-charcoal at 50 psi (3.5 kg/cm ) for 3 hours. The catalyst is then removed by filtration and washed with 100 ml of chloroform.
2~
The filtrate is stripped of chloroform, and 100 ml of hot hexane is added. The mixture is cooled and 20.0 g (72~ yield) of white precipitate is collected: m.p. 145-149C. (lit. 135-146C; see reference in Example 6).
Example 11: Preparation of 4-aza-3,3-dimethyl-4-oxyl-1-oxaspiro-~4.5]decane A solution of 32.1 g (0.19 mole)of 4-a~a-3,3-dimethyl-1-oxaspiro-[4.5]decane and 0.7 g of molybdenum hexacarbonyl, Mo(C0)6, in 75 ml of toluene is heated to 90DC and 100 ml of 4M tert-butylhydro-peroxide in toluene is added over a 30-minute period. The solution is heated for another 45 minutes at 90C to give the corresponding 4-oxyl compound in situ. The starting substituted oxazolidine is prepared by the method given in J. ~m. Chem. Soc. 66, 1738 (1944).
The 4-oxyl compound is described in J. Am. Chem. Soc. 89, 3054 (1967).
Example 12: Preparation oE 2,2,4-trimethyl-2-phenyl-3-oxyloxazolidine When using the procedure of Example ll, an equivalent amount of 2,4,4-trimethyl-2-phenyloxazolidine is substituted Eor the 4-aza-3,3-dimethyl-l-oxaspiro~4.5]decane, the above-named compound is prepared.
Claims (7)
1. A process for the preparation of a nitroxyl of the formula I
(I) wherein the nitrogen atom is flanked by two quaternary carbon atoms, where E1 and E3 are independently alkyl of 1 to 5 carbon atoms or phenyl, E2 and E4 are independently alkyl of 1 to 5 carbon atoms, or E1 and E2 together or E3 and E4 together or both El and E2 together and E3 and E4 together are tetramethylene or pentamethylene and T is a divalent group required to form a cyclic 5- or 6-membered ring, which comprises reacting an amine of the formula II
(II) where E1, E2, E3, E4 and T have the meanings given above, dissolved in an inert organic solvent, with an organic hydroperoxide in the presence of catalyst selected from a metal carbonyl, a metal oxide, a metal acetyl-acetonate or a metal alkoxide where the metal is selected from groups IVb, Vb, VIb, VIIb and VIII of the periodic table, at a temperature of 0 to 200°C, with the mole ratio of hydroperoxide to amine being 50:1 to 1:10.
(I) wherein the nitrogen atom is flanked by two quaternary carbon atoms, where E1 and E3 are independently alkyl of 1 to 5 carbon atoms or phenyl, E2 and E4 are independently alkyl of 1 to 5 carbon atoms, or E1 and E2 together or E3 and E4 together or both El and E2 together and E3 and E4 together are tetramethylene or pentamethylene and T is a divalent group required to form a cyclic 5- or 6-membered ring, which comprises reacting an amine of the formula II
(II) where E1, E2, E3, E4 and T have the meanings given above, dissolved in an inert organic solvent, with an organic hydroperoxide in the presence of catalyst selected from a metal carbonyl, a metal oxide, a metal acetyl-acetonate or a metal alkoxide where the metal is selected from groups IVb, Vb, VIb, VIIb and VIII of the periodic table, at a temperature of 0 to 200°C, with the mole ratio of hydroperoxide to amine being 50:1 to 1:10.
2. A process according to claim 1, wherein E1, E2, E3 and E4 are each methyl.
3. A process according to claim 1, wherein the catalyst is used in an amount of from 0.001 to 0.1 mole percent, based on the hydro-peroxide.
4. A process according to claim 1, wherein the temperature is 50 to 150°C.
5. A process according to claim 1, wherein the mole ratio of hydro-peroxide to amine is 10:1 to 1:1.
6. A process according to claim 5, wherein the hydroperoxide is tert-butyl hydroperoxide or cumene hydroperoxide.
7. A process according to claim 1, wherein the catalyst is vanadyl acetylacetonate, cobalt carbonyl, titanium (IV) isopropoxide, molybdenum hexacarbonyl or molybdenum trioxide.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US59231784A | 1984-03-22 | 1984-03-22 | |
| US592317 | 1984-03-22 |
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| Publication Number | Publication Date |
|---|---|
| CA1244031A true CA1244031A (en) | 1988-11-01 |
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ID=24370183
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000476966A Expired CA1244031A (en) | 1984-03-22 | 1985-03-20 | Process for preparing nitroxyls of sterically hindered amines |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0157738B1 (en) |
| JP (1) | JPS60237065A (en) |
| CA (1) | CA1244031A (en) |
| DE (1) | DE3569514D1 (en) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3851931T2 (en) * | 1987-09-21 | 1995-03-16 | Ciba Geigy Ag | Stabilization of a coating with sterically hindered N-hydroxy substituted amines. |
| JP2830329B2 (en) * | 1990-03-22 | 1998-12-02 | 住友化学工業株式会社 | Stabilized resin composition |
| DE4219459A1 (en) * | 1992-06-13 | 1993-12-16 | Huels Chemische Werke Ag | Process for the preparation of 2,2,6,6-tetramethylpiperidine-N-oxyl and its derivatives substituted in the 4-position |
| ES2148469T3 (en) * | 1994-11-15 | 2000-10-16 | Moreno Paolini | N-HYDROXIPIPERIDINES AS SUPEROXIDE RADICAL SWEEP AGENTS. |
| DE4446451A1 (en) * | 1994-12-23 | 1996-06-27 | Basf Ag | Process for the preparation of retinal by oxidation of retinol with oxygen in the presence of 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl and copper (I) chloride |
| FR2730241B1 (en) | 1995-02-07 | 1997-02-28 | Atofina | PROCESS FOR MANUFACTURING A COMPOSITION COMPRISING A VINYLAROMATIC POLYMER AND A RUBBER BY POLYMERIZATION IN THE PRESENCE OF A FREE STABLE RADICAL |
| FR2730240A1 (en) | 1995-02-07 | 1996-08-09 | Atochem Elf Sa | STABILIZATION OF A POLYMER BY A STABLE FREE RADICAL |
| DE19531649A1 (en) * | 1995-08-29 | 1997-03-06 | Basf Ag | Dowel compound for chemical fastening technology |
| DE19601924B4 (en) * | 1996-01-12 | 2005-01-13 | Ivoclar Vivadent Ag | Stable organic radical-containing light-curing composite material and its use and the use of a stable organic radical for the production of a dental material |
| US5849929A (en) * | 1997-09-26 | 1998-12-15 | Uniroyal Chemical Company, Inc. | Process for the preparation of imidazoline nitroxyl |
| EP1061059A4 (en) | 1998-03-03 | 2004-12-22 | Nippon Zeon Co | Polymerization-inhibiting composition, polymerization inhibitor and method for inhibiting polymerization |
| GB2344103B (en) * | 1998-11-24 | 2003-04-16 | Ciba Sc Holding Ag | Piperazinone derivatives |
| KR20010089632A (en) * | 1999-02-05 | 2001-10-06 | 에프. 아. 프라저, 에른스트 알테르 (에. 알테르), 한스 페터 비틀린 (하. 페. 비틀린), 피. 랍 보프, 브이. 스펜글러, 페. 아에글러 | Process for the preparation of 2,2,6,6-tetraalkylpiperidin-1-oxyl via 1,2,3,6-tetrahydro-2,2,6,6-tetraalkylpyridine |
| FR2791979B1 (en) * | 1999-04-08 | 2003-05-16 | Atochem Elf Sa | PROCESS FOR THE PREPARATION OF ALCOXYAMINES FROM NITROXIDES |
| DE60332012D1 (en) | 2002-05-02 | 2010-05-20 | Basf Se | STABILIZED BODY CARE AND BUDGET PRODUCTS |
| KR20060013632A (en) | 2002-05-17 | 2006-02-13 | 오쎄라 파마슈티걸즈, 인크. | Amelioration of the development of cataracts and other opthalmic diseases |
| US7825134B2 (en) | 2003-05-19 | 2010-11-02 | Othera Holding, Inc. | Amelioration of cataracts, macular degeneration and other ophthalmic diseases |
| CA2762361A1 (en) * | 2009-06-08 | 2010-12-16 | Basf Se | Novel sterically hindered amine light stabilizers |
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| US3634346A (en) * | 1969-08-15 | 1972-01-11 | Union Carbide Corp | Oxidation of cyclic amines to lactams |
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1985
- 1985-03-18 DE DE8585810115T patent/DE3569514D1/en not_active Expired
- 1985-03-18 EP EP19850810115 patent/EP0157738B1/en not_active Expired
- 1985-03-20 CA CA000476966A patent/CA1244031A/en not_active Expired
- 1985-03-22 JP JP60057671A patent/JPS60237065A/en active Granted
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| Publication number | Publication date |
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| EP0157738B1 (en) | 1989-04-19 |
| DE3569514D1 (en) | 1989-05-24 |
| JPS60237065A (en) | 1985-11-25 |
| EP0157738A1 (en) | 1985-10-09 |
| JPH0560464B2 (en) | 1993-09-02 |
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