ES2358690T3 - PROCESS FOR THE PREPARATION OF STERICALLY IMPEDED NITROXYL ETERS. - Google Patents

Abstract

A process for the preparation of a sterically hindered nitroxyl ether comprising reacting a corresponding sterically hindered nitroxyl radical with an alkyl radical, which is formed in the reaction of a ketone, aldehyde, diketone or oligoketone dialdehyde or oligoaldehyde with a hydroperoxide in the presence of a metal catalyst, with the proviso that, if the sterically hindered nitroxyl radical is 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), the ketone is not acetone.

Description

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The present invention relates to a novel process for the preparation of a sterically hindered nitroxyl ether of the corresponding sterically hindered nitroxyl radical by reacting it with a carbonyl compound and a hydroperoxide. The compounds prepared by this process are effective as stabilizers for polymers against harmful effects of light, oxygen and / or heat, as flame retardants for polymers, as rheology modifiers and as polymerization regulators.

The term sterically hindered nitroxyl radical used in the present invention is a synonym for the term sterically hindered nitroxide, which is also frequently used in the literature. Subsequently, the term sterically hindered nitroxyl ether used in the present invention is used as a synonym for sterically hindered nitroxide ether or sterically hindered alkoxyamine.

Because sterically hindered nitroxyl ethers are of considerable industrial interest, many attempts have been made to develop industrially applicable processes for their manufacture.

For example, WO 01/92228 describes a process for the preparation of nitroxyl ethers, for example hindered N-hydrocarbyloxy substituted amine compounds, by reacting the corresponding N-oxyl intermediate with a hydrocarbon in the presence of an organic hydroperoxide and a catalyst. coppermade.

WO 03/045919 describes a process for the preparation of nitroxyl ethers, for example hindered amine compounds substituted by N-hydrocarbyloxy, by reacting the corresponding N-oxyl intermediate with a hydrocarbon in the presence of an organic hydroperoxide and an iodide catalyst.

The reactions of 2,2,6,6-tetramethyl-1-oxopiperidinium chloride with ketones carrying an α-H atom for example are described by T. Ren et al. in bull. Chem. Soc. Jpn., 69, 2935-2941 (1996) and by Y.-C. Liu et al. in Chinese Journal of Chemistry, 14 (3), 252-258 (1996).

Surprisingly it has been found that sterically hindered nitroxyl ethers can be prepared by reacting a sterically hindered nitroxyl compound with a compound containing a carbonyl group, such as a ketone or an aldehyde in the presence of a hydroperoxide and a metal catalyst. .

In many cases, very high yields are achieved in short reaction times. Additionally, the concentration of the starting material can be selected very high, thus leading to excellent volume time performance. The reaction conditions are moderate when compared to other prior art processes and the reaction is very selective without concomitant formation of dimeric, trimeric or oligomeric by-products. Moreover, the current process allows the formation of sterically hindered nitroxyl ethers that have defined alkoxide residues instead of a mixture of isomers as in another state of the art processes.

Additionally, the current process allows the preparation of sterically hindered nitroxyl ethers, which cannot be prepared, or are only prepared with insufficient production with the prior art processes.

One aspect of the invention is a process for the preparation of a sterically hindered nitroxyl ether comprising reacting a corresponding sterically hindered nitroxyl radical with an alkyl radical, which is formed in the reaction of a ketone, aldehyde, diketone or oligoketone dialdehyde or oligoaldehyde with a hydroperoxide in the presence of a metal catalyst, with the proviso that, if the sterically hindered nitroxyl radical is 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), the ketone is not acetone.

The term "alkyl radical" should not be limited to a free radical but also includes a transition state between the reaction components, where the electrons are separated.

In general, the metal catalyst must be present in the reaction, in order to achieve the desired high yields. However, there are cases where the reaction can be carried out without the metal catalyst.

For example, the ketone, aldehyde, diketone or dialdehyde is of the Formula (Ia)

image 1

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where

R101 and R102 are independently hydrogen, straight or branched C1-C24 alkyl, straight or branched C2-C18 alkenyl, C2-C18 alkynyl, C5-C12 cycloalkyl, C5-C12 cycloalkenyl, phenyl, naphthyl or C7C15 alkyl; or C1-C24 straight or branched alkyl, C2-C24 straight or branched alkenyl, C5-C12 cycloalkyl, C5-C12 cycloalkenyl, C2-C18 alkynyl can be substituted by one or more - halogen, -OH, -OR122 , -NH2, -NHR122, N (R122) 2, -NHCOR122, -NR122COR122, -OCOR122, -COR122, -SO2R122, -SR122, -SOR122, -P (OR122) 3, -P (O) (OR122) 2 , P (R122) 3; or said substituted or unsubstituted straight or branched C1-C24 alkyl, substituted or unsubstituted straight or branched C2-C24 alkenyl, C5-C12 cycloalkyl, C5-C12 cycloalkenyl or C2-C18 alkynyl can also be interrupted by one or more groups -O-, -NH- or -NR122- or combinations thereof; or

said phenyl, naphthyl or phenyl C7-C15 alkyl can also be substituted by one or more halogen, -CN, -CF3, -NO2,

image2

-NHR122, -N (R122) 2, -OH, -OR122, -COR122;

with the proviso that at least one of R101 and R102 is not hydrogen;

where * denotes the point of adhesion;

R122 is straight or branched C1-C18 alkyl, straight or branched C2-C18 alkenyl, C5C10 cycloalkyl, phenyl, naphthyl, or C7-C15 phenylalkyl; Y

R103 is a direct bond, C 1 -C 24 alkylene, C 5 -C 12 cycloalkylene, phenylene, C 1 -C 6 alkylene-phenylene, C 1 -C 6 phenylene alkylene or C 1 -C 6 alkylene-C 1 -C 6 alkylene.

The alkyl radicals in the various substituents can be linear or branched. Examples of alkyl containing 1 to 24 carbon atoms are methyl, ethyl, propyl, isopropyl, butyl, 2-butyl, isobutyl, t-butyl, pentyl, 2pentyl, hexyl, heptyl, octyl, 2- ethylhexyl, t-octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, hexadecyl and octadecyl.

C5-C12 cycloalkyl is typically, cyclopentyl, methylcyclopentyl, dimethylcyclopentyl, cyclohexyl, methylcyclohexyl.

C5-C12 cycloalkenyl is for example cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, bicyclo [2.2.1] hept-2enyl which includes its isomers.

C2-C18 alkenyl is for example propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, dodecenyl which includes its isomers.

C2-C18 alkyl interrupted by at least one O atom is for example -CH2-CH2-O-CH2-CH3, -CH2-CH2-OCH3 or -CH2-CH2-O-CH2-CH2-CH2-O-CH2- CH3. This is preferably derived from polyethylene glycol. A general description is - ((CH2) a-O) b-H / CH3, where a is a number from 1 to 6 and b is a number from 2 to 10.

Any of the C2-C24 alkylene radicals are, for example, ethylene, propylene, 2,2-dimethylpropylene, tetramethylene, hexamethylene, octamethylene, decamethylene or dodecamethylene.

C1-C24 alkyl substituted by hydroxy-, cyano-, alkoxycarbonyl- or carbamide- may be, for example, 2-hydroxyethyl, 2hydroxypropyl, 2-cyanoethyl, methoxycarbonylmethyl, 2-ethoxycarbonylethyl, 2-aminocarbonylpropyl or 2 (dimethylaminocarbonyl) ethyl

When a diketone or dialdehyde is used, dimeric nitroxyl ethers can be obtained which are linked by the R3 group of the Formula (Ib). Products of the N-O-R3-O-N type can be schematically prepared, particularly when R3 is a longer alkyl spacer group. When R3 is a direct bond, N-O-acyl compounds can be obtained.

In particular the ketone or aldehyde is of the Formula (Ia)

image2

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wherein R101 and R102 are hydrogen, straight or branched C1-C24 alkyl, straight or branched C2-C18 alkenyl, C2-C18 alkynyl, C5-C12 cycloalkyl, C5-C12 cycloalkenyl, phenyl, naphthyl or C7- phenylalkyl C15 that can be substituted or not replaced by 1 to 3 OH groups.

Preferably R101 and R102 are hydrogen, straight or branched C1-C12 alkyl, the alkyl of which can be substituted or not substituted by 1 OH group.

Aldehydes and individual ketones that are particularly useful in the current process are acetaldehyde, propionaldehyde, butyraldehyde, pentanealdehyde, hexanealdehyde, 2-ethylhexanal, cyclohexylcarboxaldehyde, cyclohexenylcarboxaldehyde, nonaldehyde, pivalaldehydehydehydehydehydehydehydehydehydehydehydehydehydehydehyde, hydroxydehyde, phenohydehydehydehydehydehydehydehydehydehydehydehydehydehydehydehydehydehydehydehydehydehydehydehydehydehydehydehydehydehydehydehydehydehydehydehydehydehydedehydedehydedehydehydehydedehyde groups. , diethyl ketone, 3,3-Dimethyl-2,4-pentanedione, diisopropyl ketone, methyl isopropyl ketone, methyl n-propyl ketone, methyl cyclohexyl ketone, methyl octyl ketone in its different isomers, esters of 2-methyl acetoacetic acid, methoxyacetone, dimethyl acetal acetyl acetonedehyde, , methyl acetoacetate, dimethyl (2-oxopropyl) phosphonate, methanesulfonylacetone, hydroxy-2-methyl-pentanone and methyl pyruvate.

Mainly when asymmetric ketones are used in the reaction, the radical with greater stability is preferably formed and recombined with the nitroxyl radical. For example, when methyl isopropyl ketone is used, isopropyl nitroxyl ether is formed with high selectivity, typically in a ratio of 1:10.

The ketone or aldehyde can also be prepared and reacted in situ. For example, the corresponding alcohol is oxidized with an excess of hydroperoxide in the presence of a suitable catalyst and the resulting aldehyde or ketone is reacted in situ with a hydroperoxide and the same or a second catalyst to produce the alkyl radicals that can be sequestered by the nitroxyl radical In some cases a mixture of alcohol and ketone or aldehyde may be of advantage as starting materials.

For example, hydroperoxide is of Formula (II)

image2

wherein R104 is hydrogen, C5-C12 cycloalkyl, C1-C24 alkyl, phenyl or phenyl substituted by 1-4 C1-C4 alkyl groups.

Preferably the hydroperoxide is tert hydroperoxide. butyl, cumyl hydroperoxide or H2O2.

Particularly preferred is H2O2.

Hydroperoxide and in particular H2O2 is typically dissolved in water and can be used in a concentration of 1% to 90% by weight based on the weight of the total solution. Preferably the concentration is between 20% and 70% by weight.

Hydroperoxide and in particular H2O2 can also be prepared in situ, for example by electrolysis.

The metal catalyst can be selected from the group of transition metal catalysts or from the group of metal decatalizers with the character of Lewis Acid or from the group of ionic water soluble compounds and is preferably selected from the group consisting of scandium, titanium, vanadium, chrome, manganese, iron, cobalt, nickel, copper, zinc, gallium, germanium, yttrium, zirconium, niobium, molybdenum, ruthenium, rhodium, palladium, silver, cadmium, indian, tin, antimony, lanthanum, cerium, hafnium, tantalum, Tungsten, rhenium, osmium, iridium, platinum, gold, mercury, thallium, lead, bismuth, aluminum, magnesium, calcium, lithium, barium, boron, sodium, potassium, cesium, strontium or their combinations.

The metal catalyst can be linked to an organic or inorganic polymer structure, which provides a homogeneous or heterogeneous catalyst system.

The above-mentioned metal catalyst may contain anionic ligands commonly known in the complex chemistry of transition metals, such as anions derived from organic or inorganic acids, examples are halides, for example F-, Cl-, Br- or I- , fluoro complexes of the type BF4-, PF6-, SbF6- or AsF6-, anions of oxygen acids, alcoholates or cyclopentadiene anions or oxides.

Additional examples are: sulfate, phosphate, perchlorate, perbromate, periodate, antimony, arsenate, nitrate, carbonate, the anion of a C1-C30 carboxylic acid, such as format, acetate, trifluoroacetate, trichloroacetate, propionate, butyrate, benzoate, stearate, phenylacetate, mono-, di- or trichloro- or -fluoroacetate, sulphonates, for example methylsulfonate, ethyl sulphonate, propylsulfonate, butylsulfonate, trifluoromethylsulfonate (triflate), unsubstituted or C1C4- alkyl, C1-C4 alkoxy- or halo-, especially benzyl sulfonate or Phenylsulfonate substituted by fluoro-, chloro- or bromo-, carboxylates, for example tosylate, mesylate, brosylate, p-methoxy- or p-ethoxyphenylsulfonate, pentafluorophenylsulfonate or 2,4,6-triisopropylsulfonate, phosphonates, for example methylphosphonate, ethylphosphonate, , butyl phosphonate, phenylphosphonate, p-methylphenylphosphonate or benzylphosphonate, and also C1-C12 alcoholates, such as straight or branched C1-C12 alcoholates, for example methanolate or ethanolate

Neutral and anionic ligands can also be present up to the preferred coordination number of the metal catalyst complex cation, especially four, five or six. Additional negative charges are counterbalanced by cations, especially monovalent cations such as Na +, K +, NH4 + or (C1-C4 alkyl) 4N +. These neutral and anionic ligands can be applied to adjust the reactivity of the corresponding transition metal, for example in order to decrease the activity of the catalyst.

Neutral ligands are commonly known in the chemistry of transition metal complexes. Suitable inorganic ligands are selected from the group consisting of water (H2O), amino, nitrogen, carbon monoxide and nitrosyl. Suitable organic ligands are selected from the group consisting of phosphines, for example (C6H5) 3P, (i-C3H7) 3P, (C5H9) 3P or (C6H11) 3P, di-, tri-, tetra- and hydroxyamines, such as ethylenediamine, ethylenediaminetetraacetate (EDTA), N, N-dimethyl-N ', N'-bis (2-dimethylaminoethyl) -ethylenediamine (Me6TREN), catechol, N, N'-dimethyl-1,2-benzenediamine, 2- (methylamino ) phenol, 3- (methylamino) -2-butanol or N, N'-bis (1,1-dimethylethyl) -1,2ethanediamine, N, N, N ', N ", N" -pentamethylene ethiethyltriamine (PMDETA), glycols C1-C8 or glycerides, for example ethylene or propylene glycol or its derivatives, for example di-, tri- or tetraglyme, and monodentate and bidentate e-heterocyclic donor ligands.

The metal catalyst, in particular the transition metal catalyst may additionally contain e-heterocyclic donor ligands that are derived, for example, from substituted or unsubstituted heteroarenos of the group consisting of furan, thiophene, pyrrole, pyridine, bis-pyridine , picolylimine, phenanthroline, pyrimidine, bis-pyrimidine, pyrazine, indole, leave, coumarone, thionaphthene, carbazole, dibenzofuran, dibenzothiophene, pyrazole, imidazole, benzimidazole, oxazole, thiazole, bis-thiazole, isoxazole, isothiazole, quinoline, bis-quinoline , isoquinoline, bis-isoquinoline, acridine, chromene, phenazine, phenoxazine, phenothiazine, triazine, thiantrene, purine, bis-imidazole and bis-oxazole.

For example, the metal catalyst is a salt or complex of Ag, Mn, Fe, Cu, Zr, Na, Mg, Ca, Al, Pd, In, Bi or Ce in any oxidation state.

For example, the metal catalyst is a salt or a complex of Fe, Cu, Mn, Na, Mg, Pd, In, Zr or Bi in any oxidation state.

Preferably the metal catalyst is a Fe2 + or Fe3 + salt, a Cu + or Cu2 + salt, a Na + salt or a Ca2 + salt.

In the case of Na +, the use of halite (road salt, salt for cattle) may be advantageous.

The metal catalyst is typically present in an amount of 0.0005 to 10.0 molar equivalents, metal dependent. Cu, for example, is preferably used in amounts of 0.0005 to 0.2 molar equivalents and more preferably 0.005 to 0.05 molar equivalents, based on the molar equivalents of the sterically hindered nitroxyl radical. Na, for example, is preferably used in amounts of 0.005 to 3.0 molar equivalents and more preferably 0.01 to 2.0 molar equivalents, based on the molar equivalents of the sterically hindered nitroxyl radical.

The process is typically carried out at normal atmospheric pressure. In the case of aldehydes or ketones with very low boiling points, it may be advantageous to apply pressure during the reaction.

The reaction time is usually short, depending on the sterically hindered nitroxyl radical used. For example the reaction time varies from 0.5 hours to 20 hours, for example this is from 1 hour to 7 hours.

The reaction is typically carried out at a temperature between 0 ° and 100 ° C depending on the catalyst used. For example, if Cu is used, the reaction temperature is in particular between 10 ° and 60 ° C and preferably between 25 ° and 50 ° C. If Na is used, the reaction temperature is preferably between 25 and 120 ° C, more preferably between 60 and 100 ° C.

The pH value may vary from 1 to 10. Preferably this is neutral to highly acidic, for example pH 4 to 6. In the case of ketones the pH is preferably between 2.5 and 4.

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A variety of organic and inorganic acids can be used to maintain the pH value in the preferred range, examples of organic and inorganic acids have already been mentioned above. Typical examples are HCl, H2SO4, H3PO4, CH3COOH, CH3SO3H or buffer systems based, for example, on H3PO4 or CH3COOH.

The reaction can be carried out with or without additional solvent. In some cases this may be advantageous when the reaction is carried out in a two phase system, for example a phase that has water. Two-phase systems may also prevail in those cases, where aldehyde or ketone is not completely soluble in the aqueous phase. The sterically hindered nitroxyl radical may be in the aqueous phase or in the organic phase and the ketone or aldehyde in the other respective phase. In the case of immiscible phases, it may be advantageous to apply a phase transfer catalyst, typically an amphiphilic molecule or a suitable inert co-solvent. Typical phase transfer catalysts are salts containing anions, such as halides, hydroxides, hydrogen sulfates, tetraalkylammonium phosphates and alkyl arylphosphonium compounds. Current examples of phase transfer processes can be found, for example, in the Chemical Industry Digest (2005), 18 (7), 49-62, Topics in Catalysis (2004), 29 (3-4), 145 -161 or in Catalysis Interface (2003), 159-201.

Typical inert solvents are, for example, water, alkanes, toluene, xylene, nitrobenzene, acetic acid, esters such as ethyl acetate, alcohols such as ethanol or tert-butanol, halogenated solvents such as methylene chloride or chlorobenzene, ionic liquids, ethers such as tetrahydrofuran or tert-butyl methyl ether, NMP or supercritical carbon dioxide. Basically, all stable hydroperoxide solvents (for example, stable hydrogen peroxide) can be used in this process. As mentioned above, alcohols can be used as co-solvents in the current process, in particular those that form the aldehyde or ketone used after oxidation. For example, ethanol can be used in such processes, where the species that forms the radical is acetaldehyde.

Aldehyde or ketone and hydroperoxide can be used in a wide concentration range. They are typically used in an excess amount, compared to the sterically hindered nitroxyl radical. Typically for the aldehyde or ketone it is an excess of 1.05 to 20 mol equivalents, for example 1.25 to 5 mol equivalents, based on the molar amount of the sterically hindered nitroxyl radical. Hydroperoxide is typically used in an excess of 1 to 10 mol equivalents, for example 1.5 to 3 mol equivalents, based on the molar amount of the sterically hindered nitroxyl radical.

The reaction can be carried out in several ways. For example, the sterically hindered nitroxyl radical dissolves in the aldehyde or ketone. If necessary, an inert co-solvent is added. To this solution is added an aqueous solution of the hydroperoxide and after a short time of stirring the metal catalyst is added dissolved in water or in an appropriate solvent or directly, for example, in the form of a powder. The mixture is stirred and reacted for an appropriate time. In another embodiment of the process it is possible to dissolve the aldehyde or ketone in an appropriate solvent and add the hydroperoxide later. After a certain time the hindered nitroxide radical is dissolved in an appropriate solvent or alone, followed by the catalyst. It is also possible to dissolve the hindered nitroxyl radical in an appropriate solvent, add the catalyst and then add the aldehyde or ketone and hydroperoxide during the course of time - simultaneously or one after the other. Preferably, the oxidant is added over the course of time to a solution of the hindered nitroxyl radical and the aldehyde or ketone and the metal catalyst in an appropriate solvent or the oxidant and the aldehyde or ketone are added to a solution over the course of time. of the hindered nitroxyl radical and the metal catalyst.

It is possible to use aldehyde / ketone at the beginning of the full amount or only a part of it. The remaining amount can then be dosed in the reaction mixture for the desired time. The hydroperoxide and the metal catalyst may be fine to be completely added initially to the reaction mixture or added in portions for a certain time.

For example, the sterically hindered nitroxyl radical contains a structural element of Formula (Xa) or is of Formula (Xb)

image2

wherein G1, G2, G3 and G4 are independently alkyl of 1 to 4 carbon atoms or G1 and G2 and / or G3 and G4 are together tetramethylene or pentamethylene and * indicates a valence;

image2

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where

R201, are each independently of each other hydrogen, halogen, NO2, cyano, P (O) (OC2H5) 2, CONR205R206, - (R209) COOR204, -C (O) -R207, -OR208, -SR208, - NHR208, -N (R208) 2, carbamoyl, di (C1C18 alkyl) carbamoyl, -C (= NR205) (NHR206); unsubstituted C1-C18 alkyl, C2-C18 alkenyl, C2-C18 alkynyl, C7-C9 phenylalkyl, C3-C12 cycloalkyl or C2-C12 heterocycloalkyl; or C1-C18 alkyl, C2-C18 alkenyl, C2-C18 alkynyl, C7-C9 phenylalkyl, C3-C12 cycloalkyl or C2-C12 heterocycloalkyl, which are substituted by NO2, halogen, amino, hydroxy, cyano, carboxy, C1- alkoxy C4, C1-C4 alkylthio, C1-C4 alkylamino or di (C1-C4 alkyl) amino; or phenyl, naphthyl, which are substituted or not substituted by C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, halogen, cyano, hydroxy, carboxy, C1-C4 alkylamino or di (C1-C4 alkyl) amino;

R204 is hydrogen, C1-C18 alkyl, phenyl, an alkali metal cation or a tetraalkylammonium cation;

R205 and R206 are hydrogen, C1-C18 alkyl, C2-C18 alkyl which is substituted by at least one hydroxy group or, taken together, form a C2-C12 alkylene bridge or a C2-C12 alkylene bridge interrupted by at least one atom O or / and NR207;

R207 is hydrogen, C1-C18 alkyl or phenyl;

R208 is hydrogen, C1-C18 alkyl or C2-C18 alkyl which is substituted by at least one hydroxy group;

R209 is C1-C12 alkylene or a direct bond; or

all R201 together form the residue of a polycyclic cycloaliphatic ring system or a polycyclic heterocycloaliphatic ring system with at least one di or trivalent nitrogen atom.

In general, sterically hindered nitroxyl radicals containing a structural element of Formula (Xa) are preferred.

For example the sterically hindered nitroxyl radical is of the Formula (Xb) or (Xc)

image2

where

R201, are each independently of each other hydrogen, halogen, NO2, cyano, P (O) (OC2H5) 2, CONR205R206, - (R209) COOR204, -C (O) -R207, -OR208, -SR208, - NHR208, -N (R208) 2, carbamoyl, di (C1C18 alkyl) carbamoyl, -C (= NR205) (NHR206); C1-C18 unsubstituted alkyl, C2-C18 alkenyl, C2-C18 alkynyl, C7-C9 phenylalkyl, C3-C12 cycloalkyl or C2-C12 heterocycloalkyl; or C1-C18 alkyl, C2-C18 alkenyl, C2-C18 alkynyl, C7-C9 phenylalkyl, C3-C12 cycloalkyl or C2-C12 heterocycloalkyl, which are substituted by NO2, halogen, amino, hydroxy, cyano, carboxy, C1- alkoxy C4, C1-C4 alkylthio, C1-C4 alkylamino or di (C1-C4 alkyl) amino; or phenyl, naphthyl, which are substituted or not substituted by C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, halogen, cyano, hydroxy, carboxy, C1-C4 alkylamino or di (C1-C4 alkyl) amino;

R204 is hydrogen; C1-C18 alkyl, phenyl, an alkali metal cation or a tetraalkylammonium cation;

R205 and R206 are hydrogen, C1-C18 alkyl, C2-C18 alkyl which is substituted by at least one hydroxy group or, taken together, form a C2-C12 alkylene bridge or a C2-C12 alkylene bridge interrupted by at least one O or / and NR8 atom;

R207 is hydrogen, C1-C18 alkyl or phenyl;

R208 is hydrogen, C1-C18 alkyl or C2-C18 alkyl which is substituted by at least one hydroxy group; R209 is C1-C12 alkylene or a direct bond; or

all R201 together form the residue of a polycyclic cycloaliphatic ring system or a polycyclic heterocycloaliphatic ring system with at least one di or trivalent nitrogen atom;

G1, G2, G3 and G4 are independently alkyl of 1 to 4 carbon atoms or G1 and G2 and / or G3 and G4 are together tetramethylene or pentamethylene; Y

A is a divalent group required to form a 5-, 6-, or 7-membered cyclic or heterocyclic ring, which is substituted

or it is not replaced by -OH, = O or by one or two organic residues containing a total of 1-500 carbon atoms and optionally 1-200 heteroatoms.

Sterically hindered nitroxyl radicals that are formed by Formula (Xc) are preferred.

In a preferred process the sterically hindered nitroxyl radical is of Formula (A) to (O)

image2

image2

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where

G1, G2, G3, G4 are independently C1-C4 alkyl and G5 is hydrogen or methyl;

R1 is H and R2 is OH;

m is 0 or 1;

R3 is hydrogen, hydroxy or hydroxymethyl, C1-C22 alkanoyl, C1-C22 alkoxycarbonyl, C1-C22 alkanoyloxy;

R4 is hydrogen, alkyl of 1 to 12 carbon atoms or alkenyl of 2 to 12 carbon atoms;

n is 1 to 4;

when n is 1, R5 is hydrogen, alkyl of 1 to 18 carbon atoms, alkoxycarbonylalkylenecarbonyl of 4 to 18 carbon atoms, alkenyl of 2 to 18 carbon atoms, glycidyl, 2,3-dihydroxypropyl, 2-hydroxy or 2- (hydroxymethyl) substituted alkyl of 3 to 12 carbon atoms whose alkyl is interrupted by oxygen, an acyl radical of an unsaturated aliphatic or aliphatic carboxylic or carboxylic acid containing 2 to 18 carbon atoms, an acyl radical of a carbamic or carboxylic acid cycloaliphatic containing 7 to 12 carbon atoms, or acyl radical of an aromatic acid containing 7 to 15 carbon atoms;

when n is 2,

R5 is alkylene of 2 to 18 carbon atoms, a divalent acyl radical of an unsaturated aliphatic or aliphatic dicarboxylic or dicarboxylic acid containing 2 to 18 carbon atoms, a divalent acyl radical of a cycloaliphatic dicarbamic or dicarboxylic acid containing 7 to 12 carbon atoms, or a divalent acyl radical of an aromatic dicarboxylic acid containing 8 to 15 carbon atoms;

when n is 3,

R5 is a trivalent acyl radical of an unsaturated aliphatic or aliphatic tricarboxylic acid containing 6 to 18 carbon atoms, or a trivalent acyl radical of an aromatic tricarboxylic acid containing 9 to 15 carbon atoms;

when n is 4,

R5 is a tetravalent acyl radical of an unsaturated aliphatic or aliphatic tetracarboxylic acid, especially 1,2,3,4-butanetetracarboxylic acid, 1,2,3,4-but-2-enotetracarboxylic acid, 1,2,3,5 -pentanotetracarboxylic acid and 1,2,4,5-pentanotetracarboxylic acid, or

R5 is a tetravalent acyl radical of an aromatic tetracarboxylic acid containing 10 to 18 carbon atoms;

p is 1 to 3;

R6 is hydrogen, alkyl of 1 to 18 carbon atoms or acyl of 2 to 6 carbon atoms or phenyl;

when p is 1,

R7 is hydrogen, phenyl, alkyl of 1 to 18 carbon atoms, an acyl radical of an unsaturated aliphatic or aliphatic carboxylic or carboxylic acid containing 2 to 18 carbon atoms, an acyl radical of a cycloaliphatic carbamic or carboxylic acid containing 7 at 12 carbon atoms, an acyl radical of an aromatic carboxylic acid containing 7 to 15 carbon atoms, or

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R6 and R7 together are - (CH2) 5CO-, phthaloyl or a divalent maleic acid acyl radical;

when p is 2, R7 is alkylene of 2 to 12 carbon atoms, a divalent acyl radical of a dicarbamic or dicarboxylic acid aliphatic or unsaturated aliphatic containing 2 to 18 carbon atoms, a divalent acyl radical of an acid

dicarbamic or cycloaliphatic dicarboxylic containing 7 to 12 carbon atoms, or a divalent acyl radical of a aromatic dicarboxylic acid containing 8 to 15 carbon atoms; when p is 3, R7 is a trivalent acyl radical of an unsaturated aliphatic or aliphatic tricarboxylic acid containing 6 to 18 atoms

carbon, or a trivalent acyl radical of an aromatic tricarboxylic acid containing 9 to 15 carbon atoms; r is 1 to 4; when r is 1, R8 is alkoxy of 1 to 18 carbon atoms, alkenyloxy of 2 to 18 carbon atoms, -NHalkyl of 1 to 18 atoms of

carbon or -N (alkyl) 2 from 2 to 36 carbon atoms; when r is 2, R8 is alkylenedioxy of 2 to 18 carbon atoms, alkenylenedioxy of 2 to 18 carbon atoms, -NH-alkylene-NH-

from 2 to 18 carbon atoms or -N (alkyl) -alkylene-N (alkyl) - from 2 to 18 carbon atoms, or R8 is 4-methyl-1,3-phenylenediamino; when r is 3, R8 is a trivalent alkoxy radical of a saturated or unsaturated aliphatic triol containing 3 to 18 carbon atoms;

when r is 4, R8 is a tetravalent alkoxy radical of a saturated or unsaturated aliphatic tretraol containing 4 to 18 atoms of carbon;

R9 and R10 are independently chlorine, alkoxy of 1 to 18 carbon atoms, -O-T1, amino substituted by 2-hydroxyethyl, -NH (alkyl) of 1 to 18 carbon atoms, -N (alkyl) T1 with alkyl of 1 to 18 carbon atoms, or N (alkyl) 2 of 2 to 36 carbon atoms;

R11 is oxygen, or R11 is nitrogen substituted by hydrogen, alkyl of 1 to 12 carbon atoms or T1;

T1 is

image2

R12 is hydrogen or methyl; q is 2 to 8; R13 and R14 are independently hydrogen or the T2 group; T2 is

image2

R15 is hydrogen, phenyl, straight or branched alkyl of 1 to 12 carbon atoms, alkoxy of 1 to 12 carbon atoms, straight or branched alkyl of 1 to 4 carbon atoms substituted by phenyl, cycloalkyl of 5 to 8 carbon atoms , cycloalkenyl of 5 to 8 carbon atoms, alkenyl of 2 to 12 carbon atoms, glycidyl, allyloxy,

Straight or branched hydroxyalkyl of 1 to 4 carbon atoms, or silyl or silyloxy substituted three times independently by hydrogen, by phenyl, by alkyl of 1 to 4 carbon atoms or by alkoxy of 1 to 4 carbon atoms;

R16 is hydrogen or silyl substituted three times independently by hydrogen, by phenyl, by alkyl of 1 to 4 carbon atoms or by alkoxy of 1 to 4 carbon atoms;

10 d is 0 or 1;

h is 0 to 4;

k is 0 to 5;

x is 3 to 6;

and is 1 to 10;

15 z is an integer such that the compound has a molecular weight of 1000 to 4000 amu, for example z may be in the range of 3-10;

R17 is morpholino, piperidino, 1-piperizinyl, alkylamino of 1 to 8 carbon atoms, especially branched alkylamino of 3 to 8 carbon atoms such as tert-octylamino, -N (alkyl) T1 with alkyl of 1 to 8 carbon atoms , or -N (alkyl) 2 of 2 to 16 carbon atoms;

R18 is hydrogen, acyl of 2 to 4 carbon atoms, carbamoyl substituted by alkyl of 1 to 4 carbon atoms, striazinyl substituted once by chlorine and once by R17, or s-triazinyl substituted twice by R17 with the condition that the two R17 substituents may be different;

R19 is chlorine, amino substituted by alkyl of 1 to 8 carbon atoms or by T1, -N (alkyl) T1 with alkyl of 1 to 8 carbon atoms, -N (alkyl) 2 of 2 to 16 carbon atoms, or the T3 group;

25 T3 is

image2

Y

R21 is hydrogen, acyl of 2 to 4 carbon atoms, carbamoyl substituted by alkyl of 1 to 4 carbon atoms, striazinyl substituted twice by -N (alkyl) 2 of 2 to 16 carbon atoms or s-triazinyl substituted twice by 30 N (alkyl) T1 with alkyl of 1 to 8 carbon atoms.

In the definitions the term "alkyl" comprises within the given limits of carbon atoms, for example methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, 2-ethylbutyl, n-pentyl, isopentyl , 1-methylpentyl, 1,3-dimethylbutyl, n-hexyl, 1-methylhexyl, n-heptyl, 2-methylheptyl, 1,1,3,3-tetramethylbutyl, 1-methylheptyl, 3-methylheptyl, n-octyl, 2-ethylhexyl , 1,1,3-trimethylhexyl, 1,1,3,3-tetramethylpentyl, nonyl, decyl, undecyl, 1-methylundecyl or dodecyl.

Examples of alkenyl are within the given limits of carbon atoms vinyl, allyl, and the branched and unbranched isomers of butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl and dodecenyl. The term alkenyl also comprises residues with more than one double bond that can be conjugated

or not conjugate, for example it may comprise a double bond.

Examples of alkynyl are within the given limits of ethynyl and propynyl carbon atoms and unbranched butomyl, pentinyl, hexinyl, heptinyl, octinyl, noninyl, decinyl, undecinyl and dodecinyl isomers. The term "alkynyl" also comprises residues with more than one triple bond that can be conjugated or not conjugated and residues with at least one triple bond and at least one double bond, for example comprises residues with a triple bond.

Examples of alkylene are within the given limits of branched and unbranched isomeric carbon atoms of vinyl, alkylene, butylene, pentylene, hexylene, heptylene, octylene, nonylene, decylene, undecylene and dodecylene.

Some examples of cycloalkyl are cyclopentyl, cyclohexyl, methylcyclopentyl, dimethylcyclopentyl and methylcyclohexyl.

Some examples of cycloalkenyl are cyclopentenyl, cyclohexenyl, methylcyclopentenyl, dimethylcyclopentenyl and methylcyclohexenyl. The cycloalkenyl can comprise more than one double bond that can be conjugated or not conjugated, for example it can comprise a double bond.

Aryl is for example phenyl or naphthyl.

Aralkyl is for example benzyl or α, α-dimethylbenzyl.

The term "alkoxy" may comprise within the limits of the given number of carbon atoms, for example methoxy and ethoxy and the branched and unbranched isomers of propoxy, butoxy, pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, decyloxy, undecyloxy, dodecyloxy, tridecyloxy, tetradecyloxy, pentadecyloxy, hexadecyloxy, heptadecyloxy and octadecyloxy.

The term halogen may comprise chlorine, bromine and iodine; For example halogen is chlorine.

The term halide can comprise fluoro, chloride, bromide or iodide.

For example, the alkali metal comprises Li, Na, K, Rb or Cs.

For example, the alkaline earth metal comprises Be, Mg, Ca, Sr or Ba.

The acyl radicals of monocarboxylic acids have, within the definitions, a residue of the Formula -CO-R ", wherein R" may remain inter alia for an alkyl, alkenyl, cycloalkyl or aryl radical as defined. Preferred acyl radicals include acetyl, benzoyl, acryloyl, methacryloyl, propionyl, butyryl, valeroyl, hexanoyl, heptanoyl, octanoyl, nonanoyl, decanoyl, undecanoyl, dodecanoyl, pentadecanoyl, stearoyl. The polyacil radicals of polyvalent acids are of the Formula (-CO) n-R ", where n is the valence, for example 2, 3 or 4.

Some examples of an aliphatic carboxylic acid are acetic, propionic, butyric, stearic acid. An example of a cycloaliphatic carboxylic acid is cyclohexanoic acid. An example of an aromatic carboxylic acid is benzoic acid. An example of an aliphatic dicarboxylic acid is malonyl, maleoyl or succinyl, or sebacic acid. An example of a residue of an aromatic dicarboxylic acid is phthaloyl.

Preferably G1 and G3 are ethyl and G2, G4 and G5 are methyl or G1 and G2 are methyl, G3 and G4 are ethyl and G5 is hydrogen or G1, G2, G3 and G4 are methyl and G5 is hydrogen.

More preferred G1, G2, G3 and G4 are methyl and G5 is hydrogen.

Preferably the sterically hindered nitroxyl radical is of the Formula (A), (B), (B '), (C), (C'), (G), (N) or (O), more preferably of the Formula ( C), (G) or (N).

In a preferred embodiment the current process leads to a sterically hindered nitroxyl ether containing a structural element of the Formula (XI)

image2

wherein G1, G2, G3 and G4 are as defined above and E has the meaning of R101 or R102 as defined above.

The individual compounds that can be prepared by the current process are for example:

image2

image2

image3

Where n is a number from 1 to 10;

image2

image2

Sterically hindered nitroxyl radicals are widely known in the art; they can be prepared by oxidation of the corresponding sterically hindered amine N-H with a suitable oxygen donor, for example by the reaction of the corresponding sterically hindered amine NH with peroxide of

5 hydrogen and sodium tungsten as described by E.G. Rozantsev et al., In Synthesis, 1971, 192; or with tert-butyl hydroperoxide and molybdenum (VI) as taught in US Patent No. 4,691,015, or obtained in an analogous manner.

Precursor compounds of sterically hindered nitroxyl radicals (sterically hindered NH compounds) are essentially known and partially commercially available. All of them can be

10 prepare by known processes. Its preparation is described, for example, in:

US-A-5,679,733, US-A-3,640,928, US-A-4,198,334, US-A-5,204,473,

US-A-4,619,958, US-A-4,110,306, US-A-4,110,334, US-A-4,689,416,

US-A-4,408,051, SU-A-768,175 (Derwent 88-138,751 / 20), US-A-5,049,604,

US-A-4,769,457, US-A-4,356,307, US-A-4,619,956, US-A-5,182,390,

15 GB-A-2,269,819, US-A-4,292,240, US-A-5,026,849, US-A-5,071,981,

US-A-4,547,538, US-A-4,976,889, US-A-4,086,204, US-A-6,046,304,

US-A-4,331,586, US-A-4,108,829, US-A-5,051,458, WO-A-94 / 12,544

(Derwent 94-177,274 / 22), DD-A-262,439 (Derwent 89-122,983 / 17), US-A-4,857,595,

US-A-4,529,760, US-A-4,477,615, CAS 136,504-96-6, US-A-4,233,412, US-A-4,340,534, WO-A-98 / 51,690 and EP-A20 1,803, in particular US 4 442 250 or US-A-6,046,304.

The oxidation can be carried out in analogy to the oxidation of 4-hydroxy-2,2,6,6-tetramethylpiperidine described in US 5,654,434 with hydrogen peroxide. Another suitable oxidation process is also described in WO 00/40550 using peracetic acid. A thorough description of the chemistry of nitroxide (nitroxyl radical) can be found, for example, in L.B. Volodarsky, V.A, Reznikov, V.I. Ovcharenko .: "Synthetic Chemistry of Stable

25 Nitroxides ", CRC Press, 1994.

A further aspect of this process includes the generation in situ of the nitroxyl compounds starting from the corresponding piperidines. For example, this can be achieved by intermediate formation of peracids, such as peracetic acid or meta-chloroperbenzoic acid, by using an excess of hydrogen peroxide in the presence of a suitable acid and ketone / aldehyde. Alternatively, suitable peracids can be used in

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the first place to generate the nitroxyl compound, followed by the direct addition of ketone / aldehyde. The addition of an additional metal catalyst that is capable of promoting the oxidation of piperidine to the corresponding nitroxyl in the presence of a suitable oxidant such as hydrogen peroxide, and ketone / aldehyde, is another possibility to develop the current process. Alternatively, a 2-stage / crucible reaction can be developed, for example by developing the oxidation of piperidine to the corresponding nitroxyl radical with hydrogen peroxide and a suitable catalyst, such as sodium tungsten or sodium carbonate, followed by addition of aldehyde, a suitable catalyst and, if required, additional hydrogen peroxide.

Sterically hindered nitroxyl ethers are useful as light and heat stabilizers, flame retardants and polymerization initiators / regulators.

The following examples illustrate the invention,

Preparation Examples

Example 1: Preparation of 1-Ethoxy-2,2,6,6-tetramethyl-piperidin-4-ol, compound 101

25.1 g (145.1 mmol) 1-oxy-2,2,6,6-tetremethyl-piperidin-4-ol (Prostab 5198, commercial product of Ciba Specialty Chemicals Inc.) is dissolved in 105 ml methyl ethyl ketone and 50 ml ( -3 eq.) Of a 30% aqueous hydrogen peroxide solution are added over a period of 10 min. After cooling to 5 ° C, 0.71 g (5 mol%) CuCl is added and the temperature of the reaction mixture is maintained between 5 and 50 ° C. After 15-30 minutes the pH of the reaction mixture is adjusted to -3.5 and The brown solution is stirred overnight at room temperature. A homogeneous green solution is obtained. 250 ml of ethyl acetate are added and the aqueous phase is separated. The organic phase It is washed successively with 10% solution of ascorbic acid, water, dilute sodium carbonate solution, dilute sodium chloride solution, and saturated sodium chloride solution A peroxide test indicates only minor amounts of hydrogen peroxide residual. The organic phase is dried over sodium sulfate and finally evaporated to complete drying under vacuum. Yield: 22.9 g (114 mmol, 78%), greenish solid. The product contains a mixture of the ethyl and methyl product substituted in a ratio of ~ 9: 1.

1 H-NMR (CDCl 3), δ (ppm): 1.12 (t, 3 H), 1.15 (s, 3H). 1.19 (s, 3H), 1.42 (m, 4H), 1.80 (dd, 2H), 3.78 (dt, 2H), 3.95 (dddd, 1H),

13C-NMR (CDCl3), δ (ppm): 14.0, 21.4, 33.5, 48.7, 60.2, 63.8, 72.7.

Example 2: Preparation of compound 102

image2

where n is a number from 1 to 10,

compound 102

a) Preparation of the nitroxyl radical precursor

5.3 g of the corresponding NH compound of compound 100 (Chimasorb 2020, a commercial product of Ciba Specialty Chemicals Inc.) are dissolved in 25 ml of ethyl acetate. To this solution are added 10 ml of water and 5.5 g of solid sodium hydrogen carbonate. Under vigorous stirring, 4.5 ml of a 40% peracetic acid solution in acetic acid is added for 20 min. While maintaining the temperature around 25 ° C. The reaction mixture turns red after a couple of minutes and is stirred for 3h. After this, the two phases are separated and the aqueous phase is discharged. The organic phase is diluted with 50 ml ethyl acetate and washed successively with

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Four. Five

water, dilute sodium carbonate solution and saline solution. The organic phase is dried over sodium sulfate and evaporated to complete drying under vacuum. Yield: 2.9 g; red oil of the corresponding nitroxyl radical.

b) Preparation of the nitroxyl propyl ether, compound 102

0.8 g of the nitroxyl obtained prepared in step a) are dissolved in 10 ml of 2-pentanone and 4 ml of 50% aqueous hydrogen peroxide are added at room temperature. The mixture is stirred for 15 min., 30 mg of CuCl is added, and the reaction mixture is stirred overnight (22h) at room temperature. The two phases are separated and the copper containing the aqueous phase is discharged. The organic phase is diluted with 50 ml of toluene and washed successively with 10% ascorbic acid solution, 0.5 N sodium hydroxide solution and saturated sodium chloride solution. The organic phase is dried over sodium sulfate and evaporated to complete drying under vacuum (60 ° C, 0.1 mbar). Yield: ~ 500 mg (approximately 60%); pale yellow foam.

Example 3: Preparation of 2-Chloro-4,6-bis [N - [(1- (cyclohexyloxy) -2,2,6,6-tetramethyl-piperidin-4-yl) butylamino] -striazine, compound 103

a) Preparation of the precursor 2-Chloro-4,6-bis [N- (1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl) butylamino] -s-triazine 5.4 g (10.1 mmol) N, N'-dibutyl-6-chloro-N, N'-bis (2,2,6,6-tetramethyl-4-piperidinyl) -1,3,5-triazine-2,4-diamine are dissolved in 25 ml of ethyl acetate. Subsequently, 10 ml of water, 3.5 g of sodium hydrogen carbonate and 3.8 g (10.1 mmol) of a 40% peracetic acid solution in acetic acid are added at 0 ° C. After 4 h at 0 ° C, others are added

1.9 g of peracetic acid and the reaction mixture is stirred at 0 ° C overnight. The mixture is diluted with toluene / hexane and washed successively with water, dilute sodium carbonate solution and saline. The organic phase is dried over sodium sulfate and evaporated to complete drying to produce 4.0 g (70%) of a red solid.

b) 1.0 g (1.8 mmol) of 2-Chloro-4,6-bis [N- (1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl) butylamino] -s-triazine prepared under a) in 15 ml of cyclohexyl methyl ketone and 5 ml (147 mmol) of a 50% hydrogen peroxide solution is added. 30 mg of CuCl is added at room temperature and the reaction mixture is stirred at room temperature for 48h. 50 ml of ethyl acetate are added and the aqueous phase is separated. The organic phase is washed successively with 10% solution of ascorbic acid, water, dilute sodium carbonate solution, dilute sodium chloride solution, and saturated sodium chloride solution. The organic phase is dried over sodium sulfate and finally Dry to complete drying under vacuum to produce a red oil. The product is purified by column chromatography (hexane / ethyl acetate 49: 1) to provide 100 mg (8%) of the pure product.

1 H-NMR (CDCl 3), δ (ppm): 0.94 (m, 6H), 1.15-1.40 (m, 39H); 1.49-1.61 (m, 10H), 1.62-1.82 (m, 8H), 2.05 (m, 4H),

3.32 (m, 4H), 3.61 (m, 2H), 5.00 (m, 2H).

13C-NMR (CDCl3), δ (ppm): 13.9, 14.0, 20.3, 20.5, 20.6, 20.8, 25.1, 25.9, 31.8, 31.9, 32.9, 34.6, 42.3, 42.5, 43.0, 43.5, 46.0, 46.1, 46.3, 60.2, 60.3, 81.9, 82.0, 164.6, 164.8, 168.9.

Example 4: Preparation of 1-Cyclohexyloxy-2,2,6,6-tetramethyl-piperidin-4-ol, compound 104

1.0 g of 1-oxy-2,2,6,6-tetramethyl-piperidin-4-ol (Prostab 5198, commercial product of Ciba Specialty Chemicals Inc.) is dissolved in 7 ml of cyclohexane carboxaldehyde and 5 ml of a 30% aqueous hydrogen peroxide solution. The emulsion is cooled to 10 ° C and 50 mg of CuCl is added. The reaction mixture is stirred overnight at room temperature to give a greenish emulsion. The two phases are separated and the organic one is washed with 10% ascorbic acid solution, water, dilute sodium carbonate solution, dilute sodium chloride solution, and saturated sodium chloride solution. The organic phase is dried over sodium sulfate. sodium and finally evaporates to complete drying under vacuum. The product is purified by column chromatography (15: 1 hexane / ethyl acetate) to provide 1.1 g (71%) of the pure product.

1H-NMR (CDCl3), δ (ppm): 1.20 (m, 18 H), 1.51 (m, 3H), 1.81 (m, 4H), 2.06 (br s, 2H), 3.63 (m, 1H), 3.98 (m, 1H).

13C-NMR (CDCl3), δ (ppm): 21.0, 25.1, 25.9, 32.8, 34.8, 48.3, 48.8, 60.3, 62.9, 82.0.

Example 5: Preparation of 1-Methoxy-2,2,6,6-tetramethyl-piperidin-4-ol, compound 105

1.5 g of 1-oxy-2,2,6,6-tetramethyl-piperidin-4-ol (8.71 mmol) (Prostab 5198, commercial product of Ciba Specialty Chemicals Inc.) are dissolved in a mixture of 20 ml of ethanol and 15 ml of 30% hydrogen peroxide. 50 mg of CuCl are added and the mixture is maintained at 50 ° C for 18h. After the addition of 100 ml ethyl acetate, the

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The organic phase is washed with 10% ascorbic acid and subsequently with water and saline. The organic phase is dried over sodium sulfate and evaporated to complete drying to produce the almost pure product. Yield: 540 mg (2.89 mmol, 33%); greenish solid.

1H-NMR (CDCl3), δ (ppm): 1.15 (t, 3 H), 1.23 (s, 3H), 1.48 (dd, 2H), 1.84 (dd, 2H), 3.63 (s, 3H), 3.97 ( dddd, 1H). 13CRMN (CDCl3), δ (ppm): 21.3, 33.6, 48.7, 60.4, 63.5, 65.9.

In analogy, the use of propanol leads to a 17% yield of 1-Ethoxy-2,2,6,6-tetramethyl-piperidin-4-ol, the use of 1-butanol leads to a 15% yield of 1 -Propoxy-2,2,6,6-tetramethyl-piperidin-4-ol.

Example 6: Preparation of 1-Propoxy-2,2,6,6-tetramethyl-piperidin-4-ol, compound 106

2.0 g of 1-oxy-2,2,6,6-tetramethyl-piperidin-4-ol (Prostab 5198, commercial product of Ciba Specialty Chemicals Inc.) is added to a mixture consisting of 5 ml of butanal and 3 ml of a 30% aqueous hydrogen peroxide. 5 ml of toluene are added under stirring. The emulsion is cooled to 5 ° C and 50 mg of CuCl is added. The reaction mixture is stirred overnight at room temperature to give a greenish emulsion. The two phases are separated and the organic one is washed with 10% solution of ascorbic acid, water, dilute sodium carbonate solution, dilute sodium chloride solution, and saturated sodium chloride solution. The organic phase is dried over sodium sulfate and finally dried to complete drying under vacuum to provide 1.9 g of the product.

1H-NMR (CDCl3), δ (ppm): 0.94 (t, 3 H), 1.14 (s, 3H), 1.21 (s, 3H), 1.47 (m, 4H), 1.80 (dd, 2H), 3.72 ( dd, 2H), 3.97 (dddd, 1H).

13C-NMR (CDCl3), δ (ppm): 11.3, 21.4, 22.3, 33.6, 48.7, 60.4, 63.8, 78.8.

Example 7: Alternative method for the preparation of 1-Propoxy-2,2,6,6-tetramethyl-piperidin-4-ol, compound 106

1.8 g of 2,2,6,6-tetramethyl-piperidin-4-ol (intermediate product of Ciba Specialty Chemicals Inc.) are suspended in 7 ml of toluene. 2.3g of a 40% solution of peracetic acid in acetic acid are added at 0 ° C and the reaction mixture is stirred at room temperature for 3h. 4.2 ml of butanal and 2.4 ml of a 30% aqueous hydrogen peroxide solution are added, followed by 50 mg of CuCl after 15 min. The reaction mixture is stirred for 1.5h at room temperature to give a greenish emulsion. The two phases are separated and the organic phase is washed with 10% ascorbic acid solution, water, dilute sodium carbonate solution, dilute sodium chloride solution, and saturated sodium chloride solution. The organic phase is dried over sodium sulfate. sodium and finally evaporated to complete drying under vacuum to provide 1.3 g of the product.

Example 8: Alternative method for the preparation of 1-Propoxy-2,2,6,6-tetramethyl-piperidin-4-ol, compound 106

1.8 g of 2,2,6,6-tetramethyl-piperidin-4-ol (intermediate product of Ciba Specialty Chemicals Inc.) are suspended in 7 ml of toluene. 3.6 ml of a 30% aqueous hydrogen peroxide solution and 0.41 g of acetic acid are added at 5 ° C and the solution is stirred at room temperature overnight. 4.2 ml of butanal are added and, after 15 min., 50 mg of CuCl are added. The reaction mixture is stirred for 18h at room temperature. The two phases are separated and the organic one is washed with 0.05M hydrochloric acid, sodium bisulfite solution, water, dilute sodium hydroxide solution, water and finally saturated sodium chloride solution. The organic phase is dried over sodium sulfate and finally evaporated to complete drying under vacuum to provide 0.38 g of the product.

Example 9: Preparation of 1-Propoxy-2,6-diethyl-4-hydroxy-2,3,6-trimethylpiperidine, compound 107

1.0 g of 2,6-diethyl-4-hydroxy-2,3,6-trimethylpiperidine-1-N-oxyl are dissolved in 5 ml of toluene. 1.1 ml of a 30% aqueous hydrogen peroxide solution and 1.4 ml of butanal are added, followed by 50 mg of CuCl after 10 min. The solution is stirred at room temperature for 1 d. The two phases are separated and the organic phase is washed with 10% ascorbic acid solution, water, dilute sodium carbonate solution, dilute sodium chloride solution, and saturated sodium chloride solution. The organic phase is dried over sodium sulfate. sodium and finally evaporated to complete drying under vacuum to provide 0.63 g of the product as a mixture of isomers.

Example 10: Preparation of 1-Octyloxy-2,2,6,6-tetramethyl-piperidin-4-ol, compound 108

20.0 g of 1-oxy-2,2,6,6-tetramethyl-piperidin-4-ol (Prostab 5198, commercial product of Ciba Specialty Chemicals Inc.) is added to a mixture consisting of 50 ml of toluene, 30 ml of 30% aqueous hydrogen peroxide and 2 ml of acetic acid. The emulsion is cooled to 15 ° C and 50 mg of CuCl is added. 50 ml of nonanal are added

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add under vigorous stirring for 60 min. The reaction mixture is stirred for 12h at room temperature to give a greenish, viscous mass. 100 ml of tert are added. butyl methyl ether. The two phases are separated and the organic one is washed twice with 4 N NaOH, water, 10% ascorbic acid solution, water, and saturated sodium chloride solution. The organic phase is dried over sodium sulfate and finally dried. to complete drying under vacuum to provide 12.3 g of the product.

1H-NMR (CDCl3), δ (ppm): 0.87 (t, 3H), 1.15 (s, 3 H), 1.18 (s, 3H), 1.27 (2s, 6H), 1.14-1.42 (m, 10H), 1.49 (m, 2H),

1.79 (dd, 2H), 3.72 (t, 2H), 3.94 (dddd, 1H).

13C-NMR (CDCl3), δ (ppm): 13.9, 21.1, 22.6, 26.4, 28.7, 29.4, 29.7, 31.9, 33.3, 48.4, 59.9, 63.4.77.1.

Example 11: bis (1-Octyloxy-2,2,6,6-tetramethyl-4-piperidyl) sebacate, compound 109

10.0 g of Bis (1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl) sebacate (Prostab 5415, commercial product of Ciba Specialty Chemicals Inc.) are dissolved in 50 ml toluene / acetic acid (1: 1 ) and 2.5 g of calcium chloride are added. 10 ml of 50% aqueous hydrogen peroxide are added, followed by 20 ml of nonanal and 0.2 g of CuCl2. The reaction mixture is stirred for 1 h at room temperature and thereafter for 10 h at 40 ° C. The mixture is pure in 100 ml of 0.1 N NaOH and subsequently extracted with methylene chloride. The organic phase is washed twice with water and then with saturated sodium chloride solution and dried over sodium sulfate. The organic phase is removed in vacuo and the residue is subjected to column chromatography on silica gel to provide 5.5 g of the product.

The NMR data are identical with those published in the literature.

Example 11b: bis (1-Octyloxy-2,2,6,6-tetramethyl-4-piperidyl) sebacate, compound 109

10.0 g of Bis (1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl) sebacate (Prostab 5415, commercial product of Ciba Specialty Chemicals Inc.) are dissolved in 40 ml toluene / tert-butanol (2: 1) and 8g of 50% aqueous hydrogen peroxide are added, followed by 18 ml of nonanal, 0.1 ml of acetic acid and 0.15 g of CuCl2. The reaction mixture is stirred for 2 h at 25-25 ° C and thereafter for 10 h at 40 ° C. The mixture is poured into 100 ml of 0.1 N NaOH and subsequently extracted with methylene chloride. The organic phase is washed twice with water and then with saturated sodium chloride solution and dried over sodium sulfate. The organic phase is removed in vacuo and the residue is subjected to column chromatography on silica gel to provide 5.4 g of the product.

Example 12: Preparation of phosphonic acid ester [1 - [(1,1-dimethylethyl) (1-phenylethoxy) amino] -2,2-dimethylpropyl] -diethyl ester, compound 110;

image2

1.0 g of N-tert-Butyl-1-diethylphosphono-2,2-dimethylpropyl nitroxide is dissolved in 5 ml of ethanol. 0.52 ml of 30% aqueous hydrogen peroxide solution are added, followed by 0.68 g 2-phenylpropionaldehyde and 20 mg of CuCl2. The mixture is stirred at 30 ° C for 12 h. The mixture is diluted with 50 ml of methylene chloride and subsequently added to 40 ml of 0.05 N NaOH. The organic phase is separated and washed successively with 1 N NaOH, 10% aqueous solution of ascorbic acid, water, 10% aqueous solution of Na2EDTA and saturated sodium chloride solution and finally dried over sodium sulfate. The organic phase is removed in vacuo and the oily residue is subjected to column chromatography on silica gel (hexane / acetone) to provide 0.79 g (58%) of pale yellow oil.

Example 13: 2-Methyl-2- [N- [1- (diethoxyphosphinyl) -2,2-dimethylpropyl] aminoxy] propionic acid methyl ester, compound 111

image2

The compound is prepared in analogy to example 12; 47% oil yield. Treatment with 0.5N of NaOH in THF / water leads to 2-Methyl-2- [N- [1- (diethoxyphosphinyl) -2,2-dimethylpropyl] aminoxy] propionic acid,

image4

image2

The compound is prepared in analogy to example 12.

The following compounds in Table 1 and Table 2 have been prepared in analogy of the nitroxyl radical

10 corresponding and the ketone or aldehyde indicated. Table 3 gives several solvents that can be used in the current process. Table 4 demonstrates the use of various metal catalysts. In Table 5 the reactions in water are sketched and in Table 6 the use of phase transfer catalysts is presented.

Table 1

Example

Ketone Product % yield

fifteen

image2 image2 80

16

image2 image2 53

17

image2 image2 60

18

image2 image2 53

19

image2 image2 60

twenty

image2 image2 18

twenty-one

image2 image2 fifteen

22

image2 image2 10

2. 3

image2 image2 92

24

image2 image2 43

25

image2 image2 40

26

image2 image2 37

27

image2 image2 2. 3

28

image2 image2 67

29

image2 image2 81

30

image2 image2 60

31

image2 image2 Four. Five

32

image2 image2 71

33

image2 image2 5

3. 4

image2 image2 25

35

image2 image2 9

36

image2 image2 3. 4

37

image2 image2 59

38

image2 image2 8 23

39

image2 image2 28

40

image2 image2 39

Table 2

Example

Aldehyde Product % yield

41

image2 image2 69

42

image2 image2 71

43

image2 image2 85

44

image2 image2 37

Four. Five

image2 image2 79

46

image2 image2 71

47

image2 image2 30

48

image2 image2 73

49

image2 image2 69

fifty

image2 image2 42

51

image2 image2 68

52

image2 image2 75

53

image2 image2 71

54

image2 image2 64

55

image2 image2 66

56

image2 image2 71

57

image2 image2 65

58

image2 image2 81

59

image2 image2 67

60

image2 image2 64

61

image2 image2 43

62

image2 image2 65

63

image2 image2 51

64

image2 image2 25 33 7

65

image2 81

66

image2 76

67

image2 image2 76

68

image2 71

69

image2 57

70

image2 image2 76

71

image2 78

72

image2 83

73

image2 image2 66

74

image2 image2 41

75

image2 image2 36 29 5

76

image2 image2 17

77

image2 image2 3. 4

78

image2 image2 80

79

image2 image2 57

80

image2 image2 63

81

image2 image2 92

82

image2 image2 66

83

image2 image2 29

Example 84: Preparation of 1-Undecyloxy-2,2,6,6-tetramethyl-piperidin-4-ol, compound 108

10.0 g of 1-oxy-2,2,6,6-tetramethyl-piperidin-4-ol (Prostab 5198, commercial product of Ciba Specialty Chemicals Inc.) is added to a mixture consisting of 40 ml of water / ethanol ( 1: 2) and 14.6 g of dodecanal. 78 mg of CuCl2, and 5.1g of 50% aqueous hydrogen peroxide are added at RT. When a white precipitate begins to form, 40 ml of a mixture of 30 ml of ethanol and 10 ml of toluene are added and the temperature rises to 45 ° C. After 6 h another 2.5 g of 50% H2O2e is added and stirring is continued until TLC shows the complete consumption of the starting material. 100 ml of tert are added. butyl methyl ether. The two phases are separated and the organic one is washed twice with 1 M NaOH, then with water, 10% ascorbic acid solution, water, and solution.

10 saturated sodium chloride. The organic phase is dried over sodium sulfate and finally dried to complete drying under vacuum to provide 15.1 g of the product; roasted oil The product can be purified by column chromatography (hexane / acetone 49: 1). Yield 9.9g; colorless oil

1H-NMR (CDCl3), δ (ppm): 0.86 (t, 3H), 1.14 (s, 3 H), 1.18 (s, 3H), 1.26 (2s, 6H), 1.14-1.52 (m, 20H), 1.79 (dd, 2H),

3.72 (t, 2H), 3.95 (dddd, 1H).

13C-NMR (CDCl3), δ (ppm): 14.0, 21.0, 22.7, 26.4, 28.7, 29.4, 29.6, 29.65, 29.7, 31.9, 33.3, 48.3, 59.9, 63.2, 77.0.

Bis (1-undecyloxy-2,2,6,6-tetramethyl-4-piperidyl) carbonate

2.5g of 1-undecyloxy-2,2,6,6-tetramethyl-piperidin-4-ol are dissolved in 12 ml 1,2-dichloroethane, 1.2 g of pyridine are added, and the solution is cooled to 0 ° C. 1.1g of trichlorophosgen dissolved in 6 ml of 1.2 dichloroethane are added over a period of 15 mins, keeping the temperature at -10 ° C. The mixture is stirred at RT for 12h. After this, the solution is diluted with 70 ml of methylene chloride, and 20 ml of saturated NH4Cl solution are added. The

5

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fifteen

twenty

25

30

35

The aqueous phase is discharged and the organic phase is subsequently washed with 30 ml of 1N HCl, 20 ml of saturated Na2CO3 solution, water, saline. The organic phase is filtered on a buchner funnel filled with silica gel and eluted with methylene chloride. The solvent of the main fraction is removed in vacuo to produce a pale yellow oil; 1.2g

1H-NMR (CDCl3), δ (ppm): 0.88 (t, 3H), 1.18 (s, 3 H), 1.19 (s, 3H), 1.26 (2s, 6H), 1.14-1.42 (m, 18H), 1.51 (m, 2H),

1.62 (dd, 2H), 1.90 (dd, 2H), 3.71 (t, 2H), 4.84 (dddd, 1H).

13C-NMR (CDCl3), δ (ppm): 14.0, 21.0, 22.7, 26.4, 28.7, 29.4, 29.6, 29.65, 29.7, 31.9, 33.1, 44.0, 59.9, 63.2, 71.0, 77.1, 154.3.

Example 85: Alternative synthesis of bis (1-undecyloxy-2,2,6,6-tetramethyl-4-piperidyl) carbonate

24.9 g of 1-oxy-2,2,6,6-tetramethyl-piperidin-4-ol (Prostab 5198, commercial product of Ciba Specialty Chemicals Inc.) are dissolved in 100 ml of anhydrous methylene chloride, and the solution is cooled to 0 ° C. 14.7g of triethylamine are added in one portion, and 21.5g of triphosgen, dissolved in 75 ml of methylene chloride, are added over a period of 2h. The red solution is stirred at RT for 8h. The reaction is quenched by the addition of 100 ml of sol. NH4Cl sat. The aqueous phase is divided and the organic phase is subsequently washed with water, 10% Na2CO3 solution, and saline. The organic phase is dried over Na2SO4 and then removed in vacuo to produce a light red solid; mp 179 ° C. 2 g of the material obtained is dissolved in 5 mol t-BuOH / toluene (4: 1), 2.8 ml of dodecanal, and 15 mg of CuCl and 1.5 ml of 30% H2O2. The mixture is stirred first at RT for the first hour and then at 40 ° C for 12h. After 5 h, another 1 ml of H2O2 is added. 30 ml of TBME are added and the organic phase is washed successively with water, 0.1 N NaOH, water, 10% EDTA-sol. and saline solution. The organic phase is dried over sodium sulfate and finally dried to complete drying under vacuum to produce a brown oil. The product is purified by column chromatography (hexane / ethyl acetate 49: 1) to provide 1.4g of the product; slightly yellow oil.

Use of different solvents

Example reaction procedure for the preparation of 1-Propoxy-2,2,6,6-tetramethyl-piperidin-4-ol in toluene:

To a solution of 11.6 mmol of 1-oxy-2,2,6,6-tetramethyl-piperidin-4-ol (Prostab 5198, commercial product of Ciba Specialty Chemicals Inc.) in 5ml toluene is added 50 mg of CuI at RT . Under stirring, 17.4 mmol of butyraldehyde are added, followed by 17.4 mmol of a 30% aqueous solution of H2O2 over a period of 25 min. The temperature is maintained between 20-25 ° C until the end of the reaction. Additional oxidant addition may be required in some cases. The organic phase is washed successively with 10% ascorbic acid solution, water, dilute sodium carbonate solution, dilute sodium chloride solution, and saturated sodium chloride solution. The organic phase is dried over sodium sulfate and finally evaporated to complete drying under vacuum. Yield: 9.05 mmol, 78%

The following compounds in Table 3 have been prepared in analogy to the corresponding nitroxyl radical, butyraldehyde and the solvents indicated.

Table 3

Solvent

Conversion of 1-oxy-2,2,6,6-tetramethyl-piperidin-4-ol (Prostab 5198)

Cyclohexane

 95

Toluene / 1-Hexene (2: 1)

90

Chlorobenzene

 76

tert-Butyl methyl ether

63

THF

 88

Ethyl acetate

62

Methylene chloride

64

DMF

80

Ethanol

 75

tert-Butanol

 76

water / tert-Butanol (1: 8)

78

Water

 85

Acetic acid

89

Water / Ethanol (1: 1)

79

Ethylene glycol

 73

Xylene

 69

Amil acetate

61

1,4-Dioxane

 83

2-Ethoxyethanol

 75

1,1,1-Trich Loroethane

67

1-Butyl-3-methylimidazolium chloride

77 *)

*) conversion after 6h at 65-68 ° C

Use of different catalysts

General reaction procedure:

To a solution of 11.6 mmol of Prostab 5198 in 5 ml of toluene is added 3.5 mol% of the catalysts shown in Table 4 at RT. Under stirring, 17.4 mmol of butyraldehyde are added, followed by 17.4 mmol of a

5 30% aqueous solution of H2O2 over a period of 25 min. The temperature is maintained between 20-25 ° C until the end of the reaction. Additional oxidant addition may be required in some cases. The organic phase is washed successively with 10% solution of ascorbic acid, water, dilute sodium carbonate solution, dilute sodium chloride solution, and saturated sodium chloride solution. The organic phase is dried over sodium sulfate and finally dry to complete drying under vacuum.

10 Table 4

Catalyst

Conversion of 1-oxy-2,2,6,6 tetramethylpiperidin-4-ol, Prostab 5198 (toluene, after 22h) Conversion of 1-oxy-2,2,6,6 tetramethylpiperidin-4-ol, Prostab 5198 (ethanol / water (2: 1), after 22h)

CuCl

 86 95

CuOAc

5 64

CuBr

 84 91

CuCl2

 65 84

Cu (OAc) 2

 8 65

CuBR2

 83 83

Cu (NO3) 2

 5 80

CuSO4

 12 93

Cu (acac) 2

 9 76

Cu (100 mesh)

3 81

Cu (OOCC3H7) 2

 67 76

Cu (gluconate) 2

 fifteen 63

Cu (CN)

 69 71

Cu (BF4) 2

 35 68

(Copper screw)

7 69

LiCl

 28

MgCl2

 29

Al2 (SO4) 3

 46

CaCl2

 58

Sc (OTf) 3

 8

Ti (OiPr) 4

 9

MnCl2

 83 Four. Five

Fe2SO4

 63 56

Co (OAc) 2

 4

NiCl2

 eleven

ZrOCl2

 72

RuCl3

 13

PdCl2

 61 66

InCl3

 92

The (OAc) 3

 17

MeReO3

 14

BiCl3

 46

CoCl2

 13

ZnCl2

 78

image5

Water reactions as solvent

Example A: Alternative method for the preparation of 1-Methoxy-2,2,6,6-tetramethyl-piperidin-4-ol:

50 g of 1-oxy-2,2,6,6-tetramethyl-piperidin-4-ol (290 mmol) (Prostab 5198, commercial product of Ciba Specialty Chemicals Inc.) are dissolved in 250 ml of water, and added 17 g (290 mmol) of sodium chloride (Fluka No. 71381).

5 51.1 g (1.16 mol) of acetaldehyde are added at once. 29.62 g of 30% hydrogen peroxide (871 mmol) are added with stirring for the mixture in such a relationship that the reaction temperature does not exceed 37 ° C. The mixture is then slowly heated to 90 ° C and stirred for 2 h additional. The mixture is cooled to 25 ° C with stirring, neutralized with sodium carbonate solution, and the peroxides are destroyed with sodium bisulfite solution. The pH is adjusted to 11-12, and the crystals are filtered and dried in vacuo at 80 ° C. Yield 32.79 g (60%).

10 The following catalysts, under varied conditions, give similar results in water:

Table 5

Catalyst

Isolated performance Observations

CuCl

48% 3 days; max 45º

Anhydrous Cu2SO4

54% 65º

Cu (OAc) 2.H2O

48% 65º

CaCl2

60% by volume 65º

ZnCl2

 54% 65º

MnCl2

 48% 65º

Mg metal

> 90% by volume 60º

metal Al

> 90% by volume 60º

metal Fe

90% by volume 60º

metal Cu

> 90% by volume 60º

metal Zn

> 90% by volume 60º

metal Ag

10% by volume 60º

NaCl

 37% 65º

LiCl

 35% 65º

CaCl2.6H2O

 46% 88th

MgCl2.6H2O

39% 97th

AlCl3.6H2O

43% 100º

CuCl2.2H2O

 58% 90º

NaCl

20% by volume acetaldehyde that replaces acetone

NaCl

 70.6% Mixture of NaCl / water / acetaldehyde, then nitroxyl in water added at 25 °; 96º

Halite (unpurified NaCl)

> 75% by volume 60-90º

Without catalyst (white)

fifteen % 92nd

The reaction time is 3 days in all experiments

Example B: Alternative method for the preparation of 1-Ethoxy-2,2,6,6-tetramethyl-piperidin-4-ol:

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10 g of 1-oxy-2,2,6,6-tetramethyl-piperidin-4-ol and 3.38 g of sodium chloride are dissolved in water (50 ml). Add to

17.1 ml of propionaldehyde once. The reaction mass is heated to 60 °, and 17.8 ml of 30% hydrogen peroxide is slowly added with stirring at 60-70 °. The mixture is stirred at 98 ° for an additional 2 h, cooled to 40 °, sodium bisulfite solution is added, and then the pH is adjusted to 11-12 when sodium carbonate solution is added. The crystals are filtered, washed with water, and dissolved in toluene. The solution is dried over sodium sulfate, and evaporated in vacuo. Yield 8.53 g (73%).

In analogy to example B

Example C: Isobutyraldehyde 1-Isopropoxy-2,2,6,6-tetramethyl-piperidin-4-ol; 76% yield.

Example D: 1-Cyclohexyloxy-2,2,6,6-tetramethyl-piperidin-4-ol cyclohexanecarboxy-aldehyde; 23% yield.

Example E: Alternative method for the preparation of 1-Methoxy-2,2,6,6-tetramethyl-piperidin-4-one:

10 g of 1-Oxi-2,2,6,6-tetramethyl-piperidin-4-one are suspended with stirring in water (30 ml). 3.43 g of sodium chloride in water (20 ml) are added, then 13.26 ml of acetaldehyde are added at once. The mixture is heated with stirring at 60 °, then slowly add 18 ml of 30% hydrogen peroxide with stirring. The mixture is heated to 90 ° and stirred for 2 h. The mixture is cooled, and the peroxides are destroyed with 10% sodium bisulfite solution (10 ml). The pH is adjusted to 11 with sodium carbonate solution. The mixture is extracted twice with toluene. The toluene phase is dried with sodium sulfate, and evaporated in vacuo. Yield 8.12 g (75%), liquid, which crystallizes slowly.

In analogy to example E

Example E1: Method of a crucible for the preparation of 1-Methoxy-2,2,6,6-tetramethyl-piperidin-4-one:

The intermediate, 1-oxy-2,2,6,6-tetramethyl-piperidin-4-one, can be produced by reacting 2,2,6,6-tetramethylpiperidin-4-one with 3 equivalents of hydrogen peroxide in excess of water, with 10% sodium carbonate added, for 5 h at 50 °. When the reaction is complete, the solution is slightly acidified with 2 N hydrochloric acid at pH 5, then 3 equivalents of acetaldehyde and one equivalent of sodium chloride are added, and two equivalents of 30% hydrogen peroxide are added slowly to 50th. The mixture is stirred at 90 ° for 2h, and then cooled. The work, as previously done in example E, gives 62% of the liquid product, which crystallizes slowly.

Example E2: Method of a crucible for the preparation of 1-Methoxy-2,2,6,6-tetramethyl-piperidin-4-one:

The intermediate, 1-oxy-2,2,6,6-tetramethyl-piperidin-4-one, can be produced by reacting 2,2,6,6-tetramethylpiperidin-4-one with 1.75 equivalents of hydrogen peroxide in a solution of 2M sodium chloride, with 1 mol% sodium tungsten added, for 12 h at 50 °. When the reaction is complete, the solution is slightly acidified with 2 N of hydrochloric acid at pH 5, then 3 equivalents of acetaldehyde and two equivalents of 30% hydrogen peroxide are added slowly at 50 °. The mixture is stirred at 90 ° for 2h, and then cooled. The work, as previously done in example E, gives 64% of the liquid product, which crystallizes slowly.

In analogy to example E

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30

35

40

Example F: 1-Ethoxy-2,2,6,6-tetramethyl-piperidin-4-one, of propionaldehyde; yield: 78%, liquid, crystallizes slowly.

Example G: Method for the preparation of 1-Ethoxy-2,2,6,6-tetramethyl-piperidin-4-one

To a solution of 76.5 g of 4-Oxo-2,2,6,6-tetramethylpiperidine-1-oxyl in 350 ml of water and 20 ml of ethanol are added 39 g of propionaldehyde, 1.5 ml of acetic acid and 0.65g of CuCl 57 ml of 30% hydrogen peroxide in water are added dropwise at RT over a period of 60 min. After 8 h another 10 ml of 30% H2O2 are added to drive the reaction to completion. After 12h the reaction mixture is extracted twice with ethyl acetate. The organic phase is subsequently washed with sodium carbonate solution, 10% ascorbic acid solution, water and saturated sodium chloride solution. After drying over sodium sulfate, the solvent is removed under vacuum to provide 82 g of an oil. blue. The compound is purified by distillation to provide 64.6g of the product.

Example H: Preparation of 1-Butoxy-2,2,6,6-tetramethyl-piperidin-4-one:

10 g of 1-Oxi-2,2,6,6-tetramethyl-piperidin-4-one are suspended with stirring in water (50 ml). 3.45 g of sodium chloride are added, then 10g (12.3 ml) of 1-pentanal (valeraldehyde) are added at once. The mixture is heated with stirring at 60 °, then 17.8 ml of 30% hydrogen peroxide is added slowly with stirring. The mixture is heated to 90 ° and stirred for 4 h. The mixture is cooled to 25 ° and extracted twice with dichloromethane. The organic phases are washed with water, dried with sodium sulfate, and evaporated in vacuo. The residue is chromatographed on silica gel with hexane / ethyl acetate 8: 2 as the eluent; yield: 26% of the colorless, liquid product.

Example I: Preparation of 1-Pentoxy-2,2,6,6-tetramethyl-piperidin-4-one:

10 g 1-Oxi-2,2,6,6-tetramethyl-piperidin-4-one is suspended with stirring in water (50 ml). 3.45 g of sodium chloride are added, then 11.6 g (14.3 ml) of 1-hexanal (capronaldehyde) are added once. The mixture is heated with stirring at 60 °, then 17.8 ml of 30% hydrogen peroxide is added slowly with stirring. The mixture is heated to 90 ° and stirred for 4 h. The mixture is cooled to 25 ° and extracted twice with dichloromethane. The organic phases are washed with water, dried with sodium sulfate, and evaporated in vacuo. The residue is chromatographed on silica gel with hexane / ethyl acetate 8: 2 as the eluent; yield: 27% of the colorless, liquid product.

Example J: Preparation of 1-Hexyloxy-2,2,6,6-tetramethyl-piperidin-4-one:

10 g of 1-Oxi-2,2,6,6-tetramethyl-piperidin-4-one are suspended with stirring in water (50 ml). 3.45 g of sodium chloride are added, then 13.2 g (16.2 ml) of 1-heptanal (oenantal) are added once. The mixture is heated with stirring at 60 °, then 17.8 ml of 30% hydrogen peroxide is added slowly with stirring. The mixture is heated to 90 ° and stirred for 4 h. The mixture is cooled to 25 ° and extracted twice with dichloromethane. The organic phases are washed with water, dried with sodium sulfate, and evaporated in vacuo. The residue is chromatographed on silica gel with hexane / ethyl acetate 8: 2 as the eluent; yield: 23% of the colorless, liquid product.

Use of phase transfer catalyst:

To a solution of 11.6 mmol of Prostab 5198 in 5 ml of toluene is added 2.5 mol% of CuCl and 2.5 mol% of the phase transfer catalyst at RT as indicated in Table 5. Under stirring, 17.4 mmol of butyraldehyde are added , followed by 17.4 mmol of a 30% aqueous solution of H2O2 over a period of 25 min. The temperature is maintained between 20-25 ° C until the end of the reaction. Additional oxidant addition may be required in some cases. The organic phase is washed successively with 10% ascorbic acid solution, water, dilute sodium carbonate solution, dilute sodium chloride solution, and saturated sodium chloride solution. The organic phase is dried over sodium sulfate and finally dried to complete drying under vacuum.

Table 6

Phase transfer catalyst

Conversion of 1-oxy-2,2,6,6-tetramethyl-piperidin-4-ol, Prostab 5198 (after 8h)

Bu4NBr

80

C16H33Me3NBr

77

MeOcT3NBr

73

18-crown-6

 78

BnBu3NBr

 82

EtPH2PBr

78

Polyethylene Glycol 400

77

Adogen® 464

79

Aliquat® 336

75

1,4,8,11-Tetraazacyclotetradecane (Ciclam)

76

Tris (3,6-dioxaheptyl) amine

 72

5

10

fifteen

twenty

25

30

35

Claims (16)

one.

A process for the preparation of a sterically hindered nitroxyl ether comprising reacting a corresponding sterically hindered nitroxyl radical with an alkyl radical, which is formed in the reaction of a ketone, aldehyde, diketone or oligoketone dialdehyde or oligoaldehyde with a hydroperoxide in the presence of a metal catalyst, with the proviso that, if the sterically hindered nitroxyl radical is 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), the ketone is not acetone.

2.

A process according to claim 1 wherein the ketone, aldehyde, diketone or dialdehyde is of the Formula (Ia)

or (Ib) image 1 where R101 and R102 are independently hydrogen, straight or branched C1-C24 alkyl, straight or branched C2-C18 alkenyl, C2-C18 alkynyl, C5-C12 cycloalkyl, C5-C12 cycloalkenyl, phenyl, naphthyl or C7C15 alkyl; or C1-C24 straight or branched alkyl, C2-C24 straight or branched alkenyl, C5-C12 cycloalkyl, C5-C12 cycloalkenyl, C2-C18 alkynyl can be substituted by one or more - halogen, -OH, -OR122 , -NH2, -NHR122, -N (R122) 2, -NHCOR122, -NR122COR122, -OCOR122, -COR122, -SO2R122, -SR122, -SOR122, -P (OR122) 3, -P (O) (OR122) 2, P (R122) 3; or said substituted or unsubstituted straight or branched chain C1-C24 alkyl, substituted or unsubstituted straight or branched C2-C24 alkenyl, C5-C12 cycloalkyl, C5-C12 cycloalkenyl or C2-C18 alkynyl can also be interrupted by one or more groups -O-, -NH- or - NR122- or their combinations; or said phenyl, naphthyl or C7C15 phenylalkyl can also be substituted by one or more halogen, -CN, -CF3, -NO2, image 1 -NHR122, -N (R122) 2, -OH, -OR122, -COR122; with the proviso that at least one of R101 and R102 is not hydrogen; where * denotes the point of adhesion; R122 is straight or branched C1-C18 alkyl, straight or branched C2-C18 alkenyl, C5 cycloalkyl C10, phenyl, naphthyl, or C7-C15 phenylalkyl; and R103 is a direct bond, C1-C24 alkylene, C5-C12 cycloalkylene, phenylene, C1-C6 alkylene-phenylene, phenyl-C1-C6 alkylene or C1-C6-alkylene-C1-C6 alkylene. 3. A process according to claim 2 wherein the ketone or aldehyde is of the Formula (Ia) image 1 wherein R101 and R102 are hydrogen, straight or branched C1-C24 alkyl, straight or branched C2-C18 alkenyl, C2-C18 alkynyl, C5-C12 cycloalkyl, C5-C12 cycloalkenyl, phenyl, naphthyl or C7- phenylalkyl C15 that can be substituted or not replaced by 1 to 3 OH groups. 5 10 fifteen twenty 25 30 4. A process according to claim 3 wherein R101 and R102 are hydrogen, straight chain C1-C12 alkyl or branched, the alkyl of which can be substituted or not substituted by 1 OH group.

5.

A process according to claim 1 wherein the hydroperoxide is of the Formula (II)

where R104 is hydrogen, C5-C12 cycloalkyl, C1-C24 alkyl, phenyl or phenyl substituted by 1-4 C1-C4 alkyl groups.

6.

A process according to claim 5 wherein the hydroperoxide is tert hydroperoxide. butyl, cumyl hydroperoxide or H2O2.

7.

A process according to claim 1 wherein the metal catalyst is a salt or complex of Ag, Mn, Fe, Cu, Zr, Na, Mg, Ca, Al, Pd, In, Bi or Ce in any state of oxidation.

8.

A process according to claim 7 wherein the metal catalyst is a salt or a complex of Fe, Cu, Mn, Na, Mg, Pd, In, Zr or Bi in any oxidation state.

9.

A process according to claim 7 wherein the metal catalyst is a Fe2 + or Fe3 + salt, a Cu + or Cu2 + salt, a Na + salt or a Ca2 + salt.

10.

A process according to claim 1 wherein the sterically hindered nitroxyl radical contains a structural element of Formula (Xa) or is of Formula (Xb)

image 1 image 1 wherein G1, G2, G3 and G4 are independently alkyl of 1 to 4 carbon atoms or G1 and G2 and / or G3 and G4 are together tetramethylene or pentamethylene and * indicates a valence; image 1 where R201, are each independently of each other hydrogen, halogen, NO2, cyano, P (O) (OC2H5) 2, CONR205R206, - (R209) COOR204, -C (O) -R207, -OR208, -SR208, - NHR208, -N (R208) 2, carbamoyl, di (C1C18 alkyl) carbamoyl, -C (= NR205) (NHR206); unsubstituted C1-C18 alkyl, C2-C18 alkenyl, C2-C18 alkynyl, C7-C9 phenylalkyl, C3-C12 cycloalkyl or C2-C12 heterocycloalkyl; or C1-C18 alkyl, C2-C18 alkenyl, C2-C18 alkynyl, C7-C9 phenylalkyl, C3-C12 cycloalkyl or C2-C12 heterocycloalkyl, which are substituted by NO2, halogen, amino, hydroxy, cyano, carboxy, C1- alkoxy C4, C1-C4 alkylthio, C1-C4 alkylamino or di (C1-C4 alkyl) amino; or phenyl, naphthyl, which are substituted or not substituted by C1C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, halogen, cyano, hydroxy, carboxy, C1-C4 alkylamino or di (C1-C4 alkyl) amino; R204 is hydrogen, C1-C18 alkyl, phenyl, an alkali metal cation or a tetraalkylammonium cation; R205 and R206 are hydrogen, C1-C18 alkyl, C2-C18 alkyl which is substituted by at least one hydroxy group or, taken together, form a C2-C12 alkylene bridge or a C2-C12 alkylene bridge interrupted by at least one atom O or / and NR207; 5 10 fifteen twenty 25 30 R207 is hydrogen, C1-C18 alkyl or phenyl; R208 is hydrogen, C1-C18 alkyl or C2-C18 alkyl which is substituted by at least one hydroxy group; R209 is C1-C12 alkylene or a direct bond; or all R201 together form the residue of a polycyclic cycloaliphatic ring system or a polycyclic heterocycloaliphatic ring system with at least one di or trivalent nitrogen atom. 11. A process according to claim 1 wherein the sterically hindered nitroxyl radical is of the Formula (Xb) or (Xc) image 1 where R201, are each independently of each other hydrogen, halogen, NO2, cyano, P (O) (OC2H5) 2, CONR205R206, - (R209) COOR204, -C (O) -R207, -OR208, -SR208, - NHR208, -N (R208) 2, carbamoyl, di (C1C18 alkyl) carbamoyl, -C (= NR205) (NHR206); unsubstituted C1-C18 alkyl, C2-C18 alkenyl, C2-C18 alkynyl, C7C9 phenylalkyl, C3-C12 cycloalkyl or C2-C12 heterocycloalkyl; or C1-C18 alkyl, C2-C18 alkenyl, C2-C18 alkynyl, C7C9 phenylalkyl, C3-C12 cycloalkyl or C2-C12 heterocycloalkyl, which are substituted by NO2, halogen, amino, hydroxy, cyano, carboxy, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkylamino or di (C1-C4 alkyl) amino; or phenyl, naphthyl, which are substituted or not substituted by C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, halogen, cyano, hydroxy, carboxy, C1-C4 alkylamino or di (C1-C4 alkyl) amino; R204 is hydrogen, C1-C18 alkyl, phenyl, an alkali metal cation or a tetraalkylammonium cation; R205 and R206 are hydrogen, C1-C18 alkyl, C2-C18 alkyl which is substituted by at least one hydroxy group or, taken together, form a C2-C12 alkylene bridge or a C2-C12 alkylene bridge interrupted by at least one O or / and NR8 atom; R207 is hydrogen, C1-C18 alkyl or phenyl; R208 is hydrogen, C1-C18 alkyl or C2-C18 alkyl which is substituted by at least one hydroxy group; R209 is C1-C12 alkylene or a direct bond; or all R201 together form the residue of a polycyclic cycloaliphatic ring system or a polycyclic heterocycloaliphatic ring system with at least one di or trivalent nitrogen atom; G1, G2, G3 and G4 are independently alkyl of 1 to 4 carbon atoms or G1 and G2 and / or G3 and G4 are together tetramethylene or pentamethylene; Y A is a divalent group required to form a 5-, 6-, or 7-membered cyclic or heterocyclic ring, which is substituted or it is not replaced by -OH, = O or by one or two organic residues containing a total of 1-500 carbon atoms and optionally 1-200 heteroatoms. 12. A process according to claim 1 wherein the sterically hindered nitroxyl radical is of Formula (A) to (O) image 1 image 1 image 1 wherein G1, G2, G3, G4 are independently C1-C4 alkyl and G5 is hydrogen or methyl; R1 is H and R2 is OH; m is 0 or 1; R3 is hydrogen, hydroxy or hydroxymethyl, C1-C22 alkanoyl, C1-C22 alkoxycarbonyl, C1-C22 alkanoyloxy; R4 is hydrogen, alkyl of 1 to 12 carbon atoms or alkenyl of 2 to 12 carbon atoms; n is 1 to 4; when n is 1, R5 is hydrogen, alkyl of 1 to 18 carbon atoms, alkoxycarbonylalkylenecarbonyl of 4 to 18 carbon atoms, alkenyl of 2 to 18 carbon atoms, glycidyl, 2,3-dihydroxypropyl, 2-hydroxy or 2- (hydroxymethyl) substituted alkyl from 3 to 12 carbon atoms whose alkyl is interrupted by oxygen, an acyl radical of an unsaturated aliphatic or aliphatic carboxylic or carboxylic acid containing 2 to 18 carbon atoms, an acyl radical of a cycloaliphatic carbamic or carboxylic acid containing 7 to 12 carbon atoms, or acyl radical of an aromatic acid containing 7 to 15 carbon atoms; when n is 2, R5 is alkylene of 2 to 18 carbon atoms, a divalent acyl radical of an unsaturated aliphatic or aliphatic dicarboxylic or dicarboxylic acid containing 2 to 18 carbon atoms, a divalent acyl radical of a cycloaliphatic dicarbamic or dicarboxylic acid containing 7 to 12 carbon atoms, or a divalent acyl radical of an aromatic dicarboxylic acid containing 8 to 15 carbon atoms; when n is 3, R5 is a trivalent acyl radical of an unsaturated aliphatic or aliphatic tricarboxylic acid containing 6 to 18 carbon atoms, or a trivalent acyl radical of an aromatic tricarboxylic acid containing 9 to 15 carbon atoms; when n is 4, R5 is a tetravalent acyl radical of an unsaturated aliphatic or aliphatic tetracarboxylic acid, especially 1,2,3,4-butanetetracarboxylic acid, 1,2,3,4-but-2-enotetracarboxylic acid, 1,2,3,5 -pentanotetracarboxylic acid and 1,2,4,5-pentanotetracarboxylic acid, or R5 is a tetravalent acyl radical of an aromatic tetracarboxylic acid containing 10 to 18 carbon atoms; p is 1 to 3; R6 is hydrogen, alkyl of 1 to 18 carbon atoms or acyl of 2 to 6 carbon atoms or phenyl; when p is 1, R7 is hydrogen, phenyl, alkyl of 1 to 18 carbon atoms, an acyl radical of an unsaturated aliphatic or aliphatic carboxylic or carboxylic acid containing 2 to 18 carbon atoms, an acyl radical of a cycloaliphatic carbamic or carboxylic acid containing 7 at 12 carbon atoms, an acyl radical of an aromatic carboxylic acid containing 7 to 15 carbon atoms, or R6 and R7 together are - (CH2) 5CO-, phthaloyl or a divalent maleic acid acyl radical; when p is 2, R7 is alkylene of 2 to 12 carbon atoms, a divalent acyl radical of an unsaturated aliphatic or aliphatic dicarboxylic or dicarboxylic acid containing 2 to 18 carbon atoms, a divalent acyl radical of a cycloaliphatic dicarbamic or dicarboxylic acid containing 7 to 12 carbon atoms, or a divalent acyl radical of an aromatic dicarboxylic acid containing 8 to 15 carbon atoms; when p is 3, R7 is a trivalent acyl radical of an unsaturated aliphatic or aliphatic tricarboxylic acid containing 6 to 18 carbon atoms, or a trivalent acyl radical of an aromatic tricarboxylic acid containing 9 to 15 carbon atoms; r is 1 to 4; when r is 1.5 R8 is alkoxy of 1 to 18 carbon atoms, alkenyloxy of 2 to 18 carbon atoms, -NHalkyl of 1 to 18 carbon atoms or -N (alkyl) 2 of 2 to 36 carbon atoms; when r is 2, R8 is alkylenedioxy of 2 to 18 carbon atoms, alkenylenedioxy of 2 to 18 carbon atoms, -NH- alkylene-NH- of 2 to 18 carbon atoms or -N (alkyl) -alkylene-N ( alkyl) - from 2 to 18 carbon atoms, or R8 is 4-methyl-1,3 10 phenylenediamine; when r is 3, R8 is a trivalent alkoxy radical of a saturated or unsaturated aliphatic triol containing 3 to 18 carbon atoms; when r is 4, R8 is a tetravalent alkoxy radical of a saturated or unsaturated aliphatic tretraol containing 4 to 18 atoms of 15 carbon; R9 and R10 are independently chlorine, alkoxy of 1 to 18 carbon atoms, -O-T1, amino substituted by 2-hydroxyethyl, -NH (alkyl) of 1 to 18 carbon atoms, -N (alkyl) T1 with alkyl of 1 to 18 carbon atoms, or N (alkyl) 2 of 2 to 36 carbon atoms; R11 is oxygen, or R11 is nitrogen substituted by hydrogen, alkyl of 1 to 12 carbon atoms or T1; 20 T1 is image 1 R12 is hydrogen or methyl; q is 2 to 8; R13 and R14 are independently hydrogen or the T2 group; 25 T2 is image 1 R15 is hydrogen, phenyl, straight or branched alkyl of 1 to 12 carbon atoms, alkoxy of 1 to 12 carbon atoms, straight or branched alkyl of 1 to 4 carbon atoms substituted by phenyl, cycloalkyl of 5 to 8 atoms of 5 10 fifteen twenty 25 30 35 carbon, cycloalkenyl of 5 to 8 carbon atoms, alkenyl of 2 to 12 carbon atoms, glycidyl, allyloxy, straight or branched hydroxyalkyl of 1 to 4 carbon atoms, or silyl or silyloxy substituted three times independently by hydrogen, by phenyl, by alkyl of 1 to 4 carbon atoms or by alkoxy of 1 to 4 carbon atoms; R16 is hydrogen or silyl substituted three times independently by hydrogen, by phenyl, by alkyl of 1 to 4 carbon atoms or by alkoxy of 1 to 4 carbon atoms; d is 0 or 1; h is 0 to 4; k is 0 to 5; x is 3 to 6; and is 1 to 10; z is an integer such that the compound has a molecular weight of 1000 to 4000 amu, for example z may be in the range 3-10; R17 is morpholino, piperidino, 1-piperizinyl, alkylamino of 1 to 8 carbon atoms, especially branched alkylamino of 3 to 8 carbon atoms such as tert-octylamino, -N (alkyl) T1 with alkyl of 1 to 8 carbon atoms , or -N (alkyl) 2 of 2 to 16 carbon atoms; R18 is hydrogen, acyl of 2 to 4 carbon atoms, carbamoyl substituted by alkyl of 1 to 4 carbon atoms, striazinyl substituted once by chlorine and once by R17, or s-triazinyl substituted twice by R17 with the proviso that the two R17 substituents may be different; R19 is chlorine, amino substituted by alkyl of 1 to 8 carbon atoms or by T1, -N (alkyl) T1 with alkyl of 1 to 8 carbon atoms, -N (alkyl) 2 of 2 to 16 carbon atoms, or the T3 group; T3 is image 1 Y R21 is hydrogen, acyl of 2 to 4 carbon atoms, carbamoyl substituted by alkyl of 1 to 4 carbon atoms, striazinyl substituted twice by -N (alkyl) 2 of 2 to 16 carbon atoms or s-triazinyl substituted twice by N (alkyl) T1 with alkyl of 1 to 8 carbon atoms.

13.

A process according to claim 12 wherein G1 and G3 are ethyl and G2, G4 and G5 are methyl or G1 and G2 are methyl, G3 and G4 are ethyl and G5 is hydrogen or G1, G2, G3 and G4 are methyl and G5 is hydrogen.

14.

A process according to claim 12 wherein G1, G2, G3 and G4 are methyl and G5 is hydrogen.

fifteen.

A process according to claim 12 wherein the sterically hindered nitroxyl radical is of Formula (A), (B), (B '), (C), (C'), (G), (N) or ( OR).

16.

A process according to claim 1 wherein the resulting sterically hindered nitroxyl ether contains a structural element of the Formula (XI)

image 1 wherein G1, G2, G3 and G4 are as defined in claim 10 and E has the meaning of R101 or R102 as defined in claim 2.