CS271981B1 - t-fz, 2,6,6-Tetramethyl-4-piperidinyl-2-propanol and its preparation - Google Patents

Abstract

The solution relates to 1-/2,2,6,6-tetramethyl-4-piperidyl/-2-propanol and methods for its preparation by hydrogenation of 2,2,6,6-tetramethyl-4-piperidylideneacetone, /2,2,6,6- -tetramethyl-4-piperidylidene/-2-propanol or /2,2,6,6-tetramethyl-4-piperidyl/-2-propanone in an organic solvent environment, at a temperature of 20 0 to 180 °C and a partial hydrogen pressure of 0.5 to 25 MPa, in the presence of a hydrogenation catalyst, for 0.5 to 24 h, or by reaction of /2,2,6,6-tetramethyl-4-piperidyl/-2-propanone and a reducing agent from the group of complex hydrides and alkali metals in an organic solvent environment, at a temperature of 0 to 120 °C, for i to 10 n. 1-[2,2,6,6-Tetramethyl-4-piperidyl]-2-propanol can be used as an intermediate for the production of light stabilizers of polymers and biologically active substances, including pharmaceuticals.

Description

The invention relates to 1-(2,2,6,6-tetramethyl-4-piperidyl)-2-propanol of formula I

(I) and a method for its preparation. 1-/2,2,6,6-Tetramethy 1-4-piperidyl^-propanol is an intermediate for the preparation of highly effective light stabilizers of polymers and biologically active substances, including drugs.

From the literature (DE 2754 113, CS 236 437) and from industrial practice, 2,2,6,6-tetramethyl-4-piperidinol is known as the main intermediate for the production of a whole range of esters, diesters and polyesters, which represent an important group of light stabilizers of polymers, of the sterically hindered amine type. It is prepared by the reduction of 2,2,6,6-tetramethyl-4-piperidone (triacetonamine) with complex hydrides or its catalytic hydrogenation. Also known is 2-(2,2,6,6-tetramethyl-4-piperidyl)-1-ethanol, which is prepared from triacetonamine by a three-step synthesis via 2,2,6,6-tetramethyl-1,2- ₍ 5,6-tetrahydropyridine-4-acetate (Chim. Heterocycl. Soedin. 1971, 7 (2) 230-4).

A new derivative of tetramethylpiperidine, 1-/2,2,6,6-tetramethyl-4-piperidyl/2-propanol of formula I, and methods for its preparation have now been discovered. The first consists in the catalytic hydrogenation of 2,2,6,6-tetramethyl-4-piperidylideneacetone, /2,2,6,6-tetramethyl-4-piperidylidene/-2-propanol or /2,2,6,6-tetramethyl-4-piperidyl/-2-propanone in an organic solvent medium, at a temperature of 20 ⁰ to 180 °C and a partial hydrogen pressure of 0.5 to 25 MPa, in the presence of a hydrogenation catalyst, for 0.5 to 24 h. As a hydrogenation catalyst, for example, Raney Nickel, Ni/Al ₂ 0 ₃ , Nl/Cr ₂ 0 ₃ , Pd/C, Pd/BaS0 ₄ , Pt/C, Pt/Al ₂ O ₃ , PtO ₂ , or others can be used. The second method of preparing 1-/2,2,6,6-tetramethyl-4-piperidyl/-2-propanol is based on the reaction of /2,2,6,6-tetramethyl-4-piperidyl/-2-propanone with a reducing agent in an organic solvent environment, at a temperature of from °C to 120 °C, for 1 to 10 h. As a reducing agent, a complex hydride can be used, for example, LiAlH, NaBH^, NaAlH ₂ , /0CH ₂ CH ₂ 0CH ₃ / ₂ or an alkali metal, for example, metallic sodium or potassium. In the case where a complex hydride is used as the reducing agent, the reaction is carried out at a temperature of 0°C to 100°C. In the case where an alkali metal is used, the reaction is carried out in a C1 to _C4 alcohol environment, at a temperature of 40°C to 120°C.

1-(2,2,6,6-Tetramethyl-4-piperidyl)-2-propanol of formula I according to the invention can be used as an intermediate for the production of light stabilizers, suitable for thermoplastic polymer substrates such as polyolefins, polyesters, polyethers, polyurethanes, polystyrenes, or others. It is also a suitable intermediate for the production of biologically active substances, including pharmaceuticals.

The following examples illustrate, but do not limit, the subject matter of the invention.

CS 271981 Bl

Example 1

19.5 g (0.1 mol) of 2,2,6,6-tetramethyl-4-piperidylideneacetone was introduced into a 100 ml autoclave, 45 ml of 2-propanol and 1.0 g of Raney Nickel were added. After the autoclave was closed, the reaction mixture was flushed with hydrogen, heated to 180 °C and heated at a pressure of 25 MPa with constant stirring for 0.5 h. After the reaction was complete, the reaction mixture was cooled to room temperature, the catalyst was filtered off and after the solvent was distilled off, the crude product was crystallized from n-hexane. 1-(2,2,6,6-tetramethyl-4-piperidyl)-2-propanol was obtained as a white crystalline product with a melting point of 79.5 - 81 °C.

Elemental analysis for ^C ₁₂ ^H 25 ^N0 ' /Mr = 199.340/;

Calculated: 72.31% C, 12.64% H, 7.03% N

Determined: 72.23% C 12.57% H 7.06% N

IR spectrum, solution in CC1 ₄ ·

3630/str./- /oH/voInéj 3450/str./ - /o _H /vi _a2 .; 2935,2845,

2885/8/ - Q /CH/; ^{1340 1375} / ^s / - <^/cH/; 1280/p./ - /0-0/; 1410/81/ - Q _/c _ _n/: cm-1 ¹ H - NMR spectrum, 10% solution in COC1 ₃ :

3.87/m/ - >CH - 0/1 H/*, 1.16 /d/ - H ₃ C - CH' - /3 H/',

1.14 - 1.05/d/ - gem. CH ₃ /12 H/;

2.33 - 0.33 /m/ - CH^*, -CH NH-ring*, -OH ; -CH ₂ - CH C /9H/ i /PP ^m _7

Example 2

39.0 g (0.2 mol) of 2,2,6,6-tetramethyl-4-piperidylideneacetone were introduced into a 250 ml autoclave, 100 ml of methanol and 2.5 g of Ni/Al ₂ 0 ₃ , with a content of 45% Ni, were added. After closing, the autoclave was flushed with hydrogen, heated to a temperature of 60 °C and heated at a pressure of 6.0 MPa with constant stirring for 12 h. After the reaction was completed, the reaction mixture was cooled to room temperature, the catalyst was filtered off and after distilling off the solvent, the crude product was distilled under reduced pressure with the collection of the fraction 72-74 °C/400 Pa, from which 1-(2,2,6,6-tetramethyl-4-piperidyl)-2-propanol was isolated.

Elemental analysis for ^c ₁₂ ^H 25 ^{N0 :}

Calculated: 72.31% C

Determined: 72.18% C

12.64% H 7.03% N

12.47% H 7.11% N

IR and ¹ H-NMR spectrum same as in example 1.

Example 3

19.7 g (0.1 mol) of /2,2,6,6-tetramethyl-4-piperidylidene/-2-propanol were placed in a 100 ml autoclave, 45 ml of cyclohexane and 0.1 g of Pt on activated carbon were added.

CS 271981 Bl with a platinum content of S %. After closing, the autoclave was flushed with hydrogen, heated to a temperature of °C and heated at a pressure of 0.5 MPa with constant stirring for 24 h. After the reaction was completed, the reaction mixture was cooled to room temperature, the catalyst was filtered off and after distilling off the solvent, the crude product was recrystallized from n-pentane. 1-/2,2,6,6-tetramethyl-4-piperidyl/-2-propanol was obtained as a white crystalline substance with a melting point of 79 -80.5 °C.

Elemental analysis for Ci2 ^H 25 ^{N0 !} calculated : 72.31% C 12.64% H 7.03%N

Determined: 72.21% C 12.53% H 7.08% N

IR- and ^H-NMR spectrum same as in example 1.

Example 4

19.7 g (0.1 mol) of /2,2,6,6-tetramethyl-4-piperidyl/-2-propanone was introduced into a 100 ml autoclave, 45 ml of ethanol and 0.2 g of Pd on BaS0 ₄ with a palladium content of 5% were added. After sealing, the autoclave was flushed with hydrogen, heated to 180 °C and heated at a pressure of 25 MPa with constant stirring for 0.5 h. After the reaction was complete, the reaction mixture was cooled to room temperature, the catalyst was filtered off and after distilling off the solvent, the crude product was crystallized from diethyl ether. 1-(2,2,6,6-tetramethyl-4-piperidyl/-2-propanol was obtained as a white crystalline substance with a melting point of 79.5 - 80.5 °C. 1 H-NMR and IR spectrum is the same as in Example 1.

r

Example 5

39.4 g (0.2 mol) of /2,2,6,6-tetramethyl-4-piperidyl/-2-propanone were placed in a 250 ml autoclave, 90 ml of n-heptane and 0.05 g of Pt0 ₂ were added. After sealing, the autoclave was flushed with hydrogen and the reaction mixture was stirred at 20 °C and 0.1 MPa for 24 h. After the reaction was complete, the catalyst was filtered off and after evaporation of 50 ml of n-heptane, the product 1-(2,2,6,6-tetramethyl-4-piperidyl/-2-propanol) crystallized from the reaction mixture as a white crystalline substance with a melting point of 79.5 - 81 °C.

Elemental analysis for C, _o H„_N0 :

1Z of

Calculated: 72.31% C 12.64% H 7.03% N

Determined: 72.25% C 12.59% H 7.09% N ^H-NMR and IR spectrum as in example 1.

Example 6

To a suspension of 7.6 g (0.2 mol) of lithium aluminum hydride in 500 ml of anhydrous diethyl ether at 0 °C with stirring was added dropwise 39.4 g (0.2 mol) of /2,2,6,6-tetramethyl-4-piperidyl/-2-propanone over 1 h. The reaction mixture was stirred for 4 h at 5 °C and 5 h under reflux of diethyl ether. After completion of the reaction, the reaction mixture was cooled to 0 °C and the product complex was decomposed with water. The precipitate formed was filtered off and washed with diethyl ether. After separation of the aqueous layer, the ether layers were combined, dried with anhydrous Na ₂ S0 ₄ and the diethyl ether was evaporated.

The crude product was crystallized from n-hexane to give 1-(2,2,6,6-tetramethyl-4-piperidyl)-1-propanol as a white crystalline solid, mp 80-81°C.

CS 271981 Bl

Elemental analysis for C. _o H _o ^N0 : 12 25 calculated : 72.31% C 12.64% H 7.03% N

Determined: 72.27% C 16.61% H 7.06% N ^H-NMR and IR spectrum as in example 1.

Example 7

To a suspension of 7.4 g (0.2 mol) in 140 g of diglyme was added at room temperature 19.7 g (0.1 mol) of /2,2,6,6-tetramethyl-4-piperidyl/-2-propanone and the reaction mixture was heated for 1 h at 100 °C with constant stirring. After the reaction was complete, the reaction mixture was cooled, the resulting complex was decomposed with a 5% NaHCO ₃ solution. The aqueous layer was separated and extracted with n-hexane. After drying the organic part with anhydrous Na ₂ S0 ₄ , the solvents were distilled off and the crude product was distilled under reduced pressure with the fraction 69-71 °C/300 Pa collected. 1-(2,2,6,6-tetramethyl-4-piperidyl)-2-propanol was obtained as a white crystalline solid with a melting point of 79-81°C.

Elemental analysis for CHNO: 12 2o

Calculated: 72.31% C 12.64% H 7.03% N

Determined: 72.09% C 12.51% H 7.11% N _y 1

IC - and H-NMR spectrum as in example 1.

Example 8

To a solution of 19.7 g (0.1 mol) of /2,2,6,6-tetramethyl-4-piperidyl/-2-propanone in 300 ml of methanol at room temperature was added in small portions 11.5 g (0.5 mol) of sodium metal. The reaction mixture was stirred at 40 °C for 10 h. After completion of the reaction, the reaction mixture was cooled to 5 °C and the complex was decomposed with water. The methanol was distilled off from the reaction mixture, the product was extracted from the aqueous layer with n-heptane and dried over anhydrous Na ₂ S0 _{4 <} after filtering off the Na ₂ S0 ₄ 1-/2,2,6,6-tetramethyl-4-piperidyl/-2-propanol was isolated by crystallization as a white crystalline product with a melting point of 79 - 80.5 °C.

Elemental analysis for C,..H„.N0 : 12 25 calculated : 72.31% c 12.64% H

7.03% N

Determined: 72.23% C 12.53% H 7.10% N

IR- and ¹ H-NMR spectrum as in example 1.

Example 9

To a solution of 39.4 g (0.2 mol) of /2,2,6,6-tetramethyl-4-piperidyl/-2-propanone in 500 ml of n-butanol at room temperature was added portionwise 23.0 g (1 mol) of sodium metal and the reaction mixture was stirred for 1 h at 120 °C. After the reaction was complete, the reaction mixture was cooled to room temperature and the complex was decomposed with water. The aqueous layer was separated after salting out the entire amount of n-butanol with NaCl. The n-butanol solution was dried over anhydrous Na ₂ S0 _4. After filtering off the Na ₂ S0 ₄ , the solvent was distilled off and the crude product was rectified under reduced pressure with the fraction 68 - 71 °C/300 Pa collected. 1-(2,2,6,6-tetramethyl-4-piperidyl)-2-propanol was obtained as a white crystalline solid with a melting point of 71-80.5°C.

CS 271981 Bl

Elemental analysis for 0^2^25^° ^: calculated : 72.31% C 12.64% H 7.03% N

Determined: 72.20% C 12.51% H 7.09% N

IR-a ¹ h-NMR spectrum as in example 1.

Claims (5)

BEFORE THE MET OF THE INVENTION 1- (2,2,6,6-Tetramethyl-4-piperidyl) -2-propanol of the formula I (I) 2. A process for the preparation of 1- (2,2,6,6-tetramethyl-4-piperidyl) -2-propanol according to item 1, characterized in that 2,2,6 ₍ 6-tetramethyl-4-piperidylideneacetone) is prepared. 2,2,6,6-tetramethyl-4-piperidilidene [-2-propanol] or [2,2,6,6-tetramethyl-4-piperid] lidene] -2-propanone is subjected to hydrogenation in an organic solvent medium at a temperature of 20 ⁰ to 180 ° C and a hydrogen partial pressure of 0.5 to 25 MPa, in the presence of a hydrogenation catalyst, for 0.5 to 24 h. 3. A process for the preparation of 1- (2,2,6,6-tetramethyl-4-piperidyl) -2-propanol according to claim 1, characterized in that (2,2,6,6-tetramethyl-4-piperidyl) The β-propanone is treated with a reducing agent in an organic solvent medium, at a temperature of ⁰ to 120 ° C, for 1 to 10 hours. 4. The process according to item 3, characterized in that a complex hydride is used as a reducing agent and the reaction is carried out at a temperature of ⁰ to 100 ° C. 5. The process according to item 3, characterized in that an alkali metal is used as the reducing agent and the reaction is carried out in a medium c. to c. alcohol, at a temperature of ⁰ to 40