SK1192007A3 - Process for preparing 2,2,6,6-tetramethylpiperidine-N-oxyl and its 4-substituted derivatives - Google Patents

Abstract

It is described a method for preparing 2,2,6,6-tetramethylpiperidine-N-oxyl and its 4-substituted derivatives by catalytic oxidation of the secondary amine hydrogen peroxide at a temperature from 20 to 100 °C. As oxidation catalyst is used carbon dioxide and sodium or potassium salt of phosphoric to polyphosphoric acid as a stabilizer of hydrogen peroxide.

Description

Technical field

The invention relates to a novel process for the preparation of 2,2,6,6-tetramethylpiperidine-N-oxyl and 4-substituted derivatives thereof, wherein the oxidation of the corresponding secondary amine is catalyzed by carbon dioxide.

BACKGROUND OF THE INVENTION

The preparation of nitroxyls by oxidation of the corresponding secondary amines is described in the literature. The difference between the processes is mainly in the oxidizing agent used and the catalysts used.

Various organic peroxyacids, e.g. peroxyacetic acid (WO 2004/85397), 3-chloroperoxybenzoic acid [J. Org. Chem. 39, (1947), 2356, 2360], dibenzoyl peroxide (FR 1 360 030), tert-butyl peroxide [EP 157 738; Maender O.W. et al., J. Org. Chem. 34, 4072 (1969)] and ozone [Razumovskii S.D. et al .: Doc. Akad. Teachings. USSR 183,1106 (1969)].

Compared to these oxidizing agents, the use of hydrogen peroxide is preferable because it is cost effective and only water is produced as the product of the reaction. Various catalysts are used in the oxidation.

Tungstic acid catalyzed hydrogen peroxide oxidation is described in the literature [GB 1 199 351; Tetrahedron 20 (1964), 131-7].

Raztantev salts were also used by tungsten (sodium) salts (Izv. AN USSR 1966, 1466; Synthesis 1984, 902) to oxidize 4-aminotetramethylpiperidine.

U.S. Patent No. 5,817,824 describes the oxidation of 4-oxo-tetramethylpiperidine with hydrogen peroxide using sodium tungsten as a catalyst, in the presence of a peroxide stabilizer, ethylenediaminotetraacetic acid, to shorten the reaction time to 3 to 7 h, in combination with C 1 to C 25 alcohols.

A disadvantage of these processes is the relatively long reaction time and the problem of removal of the catalyst, which must not be allowed to enter the waste water for environmental reasons.

Hils (DE 4 219 459) achieves a high yield and purity of the product when oxidizing 4-hydroxytetramethylpiperidine with 30% hydrogen peroxide catalyzed by alkaline earth metal or zinc salts (preferably magnesium) at 70 ° C.

Enichem (EP 488 403) describes titanium dioxide deposited on silica as a catalyst for the oxidation of sterically shielded amines.

Ecologically acceptable processes appear from Ciba Geigy (US 5,654,434), which prepares 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl by oxidation of the corresponding amine with hydrogen peroxide at 80 to 99 ° C without the use of a catalyst. , preferably using ethylenediaminotetraacetic acid disodium salt (US 5,654,434), or in the presence of a catalytic amount of ammonium or alkali metal carbonate or bicarbonate, at a temperature of 60 to 99 ° C (US 5,629,426).

While 4-hydroxy-2,2,6,6-tetramethylpiperidine can be oxidized with a catalytic amount of alkali or ammonium carbonates or bicarbonates according to US 5,629,426 to oxidize triacetonamine (4-oxo-2,2,6,6) -tetramethylpiperidine) according to Zakrzewski [Zakrzewski J .: Journal f. Pract. Chemie, 1985, 327 (6), 1011-1014] uses a three-fold molar amount of sodium carbonate and a 14-fold molar amount of 30% hydrogen peroxide. The reaction was carried out with cooling for 48 h. Under the above conditions, a 73% yield of oxy-4-oxo-TEMPO was achieved. Oxidation of triacetonamine in the presence of 10% by weight, ethylenediaminotetraacetic acid and 10% by weight, with sodium tungsten with 30% hydrogen peroxide after 1 week gave 4-oxo-TEMPO in 25-33% yield with formation of four by-products.

SK 260 755 describes a process for the preparation of 4-substituted 2,2,6,6-tetramethylpiperidines by oxidation with hydrogen peroxide, optionally in an organic solvent environment, optionally in the presence of a catalyst and Chelaton 3, wherein the reaction mixture is sonicated.

SUMMARY OF THE INVENTION

The present invention provides a process for the preparation of 2,2,6,6-tetramethylpiperidine-N-oxyl and its 4-substituted derivatives by catalytic oxidation of the corresponding secondary amine with hydrogen peroxide, optionally in the presence of hydrogen peroxide stabilizers, wherein carbon dioxide is used as the oxidation catalyst. the reaction is carried out at a temperature of 20 to 100 ° C.

Advantages of the process of the present invention include the fact that it eliminates the need to use heavy metals as oxidation catalysts. Nor is it necessary to use expensive ethylenediaminotetraacetic acid, respectively. its disodium salt as an inhibitor of hydrogen peroxide decomposition.

A further advantage is that the conversion of carbon dioxide results in high raw material conversions, i. the reaction time is shortened and a high yield is obtained even at relatively low temperatures.

DETAILED DESCRIPTION OF THE INVENTION

Example 1 - Comparative

100 g of 4-hydroxy-2,2,6,6-tetramethylpiperidine (HTMP), 80 g of water and the recommended catalyst (s) were dosed into a 11-sulfonation flask equipped with a stirrer, reflux condenser, thermometer, and feed tube. hydrogen peroxide decomposition stabilizer.

The mixture was heated to 60 ° C, allowed to homogenize by stirring for 30 minutes. Dosing of 50% hydrogen peroxide was carried out for 2 h at 60 ° C, and the reaction was continued for 4 h at 60 ° C.

The results of the conversion of HTMP and hydrogen peroxide during post-reaction are shown in Table 1.

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Tab. 1: Effect of reaction time on the conversion of HTMP with known inhibitors, respectively. catalysts at 60 ° C

Marking the experiment Collection time [Min] The catalyst, respectively. inhibitor stick h ₂ o ₂ HTMP oh WITH K? O g £ S E- (S ^f ~~ ^l O g KÄ Contents [wt%] 1 ' conversion [%] Contents [wt%] conversion [%] HTO-1 0 - 0.8 1.8 0.61 96.0 21.0 45.7 60 0.15 99.0 20.1 48.0 120 0.15 99.0 20.0 48.2 180 0.16 99.0 19.8 48,8 240 0.15 99.0 20.5 47.0 HTO-2 0 0.51 g of disodium salt of ethylenediaminotetraacetic acid 0.8 1.8 1.2 92.0 27.0 30.0 60 0.2 98.7 24.9 35.5 120 0.2 98.7 26.8 30.5 180 0.2 98.7 27.8 27.7 240 <0.1 > 99.3 24.8 35.6 HTO-3 0 0,5 g MgSO ₄ (anhydrous) 0.8 1.8 10.8 28.8 26.00 32.5 60 6.7 55.8 15.72 . 59.2 120 5.8 61.8 12.44 67.7 180 4.2 72.3 11,30 70.7 240 3.9 74.3 6.94 the next day 82.0 HTO-4 0 0.51 g NaHCO 3 0.8 1.8 0.3 98.0 21.5 44.4 60 <0.1 > 99.3 20.3 47.5 120 <0.1 > 99.3 21.7 44.0 180 <0.1 > 99.3 20.8 46.2 240 <0.1 > 99.3 21.6 44.1 HTO-5 0 2.24 g (NH ₄ ) ₂ CO ₃ (aqueous solution) 0.8 1.8 28.8 25.0 120 29.4 23.3 240 28.2 26.5

Example 2

The addition of carbon dioxide was tested in the apparatus of Example 1 with the same batches. Carbon dioxide was metered into the reaction solution prior to the addition of hydrogen peroxide from the pressurized bomb. From the weight gain before and after the addition, the amount retained was determined.

The hydrogen peroxide dosing was carried out for 2 h at 60 ° C, and the reaction was continued for 4 h at 60 ° C.

The results of HTMP oxidation in the presence of carbon dioxide are summarized in Table 2.

Tab. 2: Effect of reaction time on HTMP conversion in the presence of carbon dioxide at ° C

Marking the experiment Collection time [Min] catalyst Cn s ® 1—1 > o 8R stick h ₂ 0 ₂ HTMP C- WITH K £ o § <n K ŕL PH 2 H The rú * T O 2 M Contents [wt%] conversion [%] Contents [wt%] conversion [%] HTO-6 0 17.9 g CO ₂ 0.6 0.8 1.8 3.5 75.3 5.0 86.1 60 0.8 94.4 3.3 91.0 120 0.2 98.6 2.7 92.5 180 0.1 99.3 2.0 94.4 240 <0.1 > 99.3 1.75 95.2 HTO-7 0 1.2 g co ₂ 0.04 0.8 1.8 2.3 84.7 5.0 86.9 60 0.7 95.3 3.8 90.2 120 0.1 99.3 3.1 91.8 180 <0.1 > 99.3 2.5 93.5 240 <0.1 > 99.3 2.2 94.3

Example 3

In the apparatus of Example 1, the oxidation course of 100 g of 4-oxo-2,2,6,6-tetramethylpiperidine (OTMP) was tested after dilution of 80 g of water with various catalyst additions for comparison and carbon dioxide addition.

The hydrogen peroxide dosing was carried out for 2 h at 60 ° C, and the reaction was continued for 4 h at 60 ° C.

The results of the OTMP conversion measurements are shown in Table 3.

Tab. 3: OTMP oxidation process with different catalysts, resp. hydrogen peroxide decomposition inhibitors at 60 ° C

Marking the experiment Collection time [Min] The catalyst, respectively. inhibitor stick H ₂ O ₂ OTMP WITH h 77 O £ d g rt H K £ S H O C4 ¹ ~ ¹ C 2 Contents [wt%] conversion [%] Contents [wt%] conversion [%] OTO-1 0 - 0.8 1.8 8.3 45.6 24.2 37.4 60 5.0 67.2 19.5 49.7 120 3.3 78.4 16.8 56.7 180 2.0 86.9 13.7 64.5 240 1.4 90.8 13.8 64.4 OTO-2 0 2.01 g MgSO ₄ (anhydrous) 0.8 1.8 15.2 0.0 23.4 39.0 60 10.6 29.5 14.5 62.2 120 7.6 49.4 8.5 77.8 180 7.5 50.1 6.2 83.8 240 5.9 60.7 4.7 87.8 OTO-3 0 2,0 g Chelaton-III 0.8 1.8 14.0 7.5 29.3 23.5 60 10.5 30.6 17.0 55.6 120 6.8 55.1 10.2 73,4 180 5.2 65.6 7.6 80.3 240 4.9 67.6 6.6 82.9 OTO-4 0 0.75 g of CO ₂ CO ₂ / 0.03 = OTMP 0.8 1.8 8.8 42.2 11.2 71.0 60 5.7 62.6 6.2 83.9 120 3.7 75.7 4.6 88.0 180 3.1 79.6 4.0 89.5 240 2.3 84.9 3.7 90.3

Example 4

In the apparatus of Example 1, oxidation of 100 g of 2,2,6,6-tetramethylpiperidine (TMP) in the reaction medium was carried out with 80 g of methanol instead of the water used in Examples 1 to 3. The other reaction conditions were maintained.

The hydrogen peroxide dosing was carried out for 2 h at 60 ° C, and the reaction was continued for 4 h at 60 ° C.

The results are summarized in Table 4.

Table 4: Progress of TMP oxidation after dosing of hydrogen peroxide at 40 ° C

Marking the experiment Collection time [Min] The catalyst, respectively. inhibitor stick H ₂ O ₂ TMP MeOH / TMP [Wt.] P- S h (N ¹ --- Ί O 2 rl t K Contents [wt%] conversion [%] Contents [wt%] conversion [%] TEMPO-1 0 0.8 1.8 2.8 82.8 27.8 25.6 60 0.9 94.5 27.7 25.9 120 0.4 97.5 28.9 22.6 180 0.2 98.8 28.7 23.3 240 0.1 99.4 28.8 23.0 TEMPO-2 0 2.02 g MgSO ₄ (anhydrous) 0.8 1.8 13.8 14.9 21.5 41.9 60 9.1 43.9 14.0 62.1 120 7.7 52.5 10.8 70.9 180 7.3 55.0 8.6 76.8 240 6.3 61.1 6.1 83.4 TEMPO-3 0 2,01 g Chelaton-III 0.8 1.8 6.7 58.2 16.3 56.0 60 1.9 88.1 13.3 64.0 120 0.7 95.6 10.4 71.9 180 0.3 98.1 10,0 73.1 240 0.1 99.4 9.9 73.3 PACE 0 2.18 g of CO ₂ C0 ₂ / TMP-0.07 0.8 1.8 1.9 88.2 7.95 78.5 60 0.5 96.9 4.5 87.8 120 0.2 98.8 2.9 92.1 180 0.1 99.4 2.6 92.9 240 0.1 99.4 2.4 93.6

Example 5

Oxidation of 2,2,6,6-tetramethylpiperidine, 4-hydroxy-2,2,6,6-tetramethylpiperidine and 4-oxo-2,2,6,6-tetramethylpiperidine was performed at 40 ° C. Hydrogen peroxide was added to the HTMP batch as in Example 1, to the OTMP batch as in Example 3, and to the TMP batch as in Example 4 after addition of carbon dioxide. The reaction lasted 2 h, samples were analyzed at time 0 after addition and at 60 minute intervals.

The results are shown in Table 5.

Tab. 5: Progress of HTMP, OTMP and TMP oxidation after addition of hydrogen peroxide at 40 ° C

Marking the experiment Subscription time [min] co ₂ [g] stick raw material H ₂ O / raw material [wt] H ₂ O ₂ / HTMP [mol] Contents [wt%] conversion [%] HTO-8 0 4.5 0.8 1.8 9.5 75.0 60 7.3 80.9 120 5.6 86.2 180 4.6 86.9 240 3.9 89.7 OTO-5 0 1.26 0.8 1.8 10.5 72.6 60 5.2 86.3 120 3.9 89,8 180 3.4 91.2 240 2.8 92.6 TEMPO-5 0 2.56 0.8 1.8 7.0 81.2 60 4.1 88.8 120 3.3 91.1 180 3.1 91.5 240 2.9 92.2

Example 6

After surprising results of the conversion of shielded amines in the presence of carbon dioxide at 40 ° C, the oxidation of 4-oxo-2,2,6,6-tetramethylpiperidine was also carried out at 20 ° C and the oxidation of 4-hydroxy-2,2,6, 6-tetramethylpiperidine at 90 ° C in the presence of sodium hexametaphosphate as a hydrogen peroxide stabilizer.

The batch was the same as in Example 3, carbon dioxide was used in an amount of 1.1 g (CO ₂ : OTMP molar ratio = 0.04) and the hydrogen peroxide feed time was 2 h.

The oxidation results are shown in Table 6.

Tab. 6: OTMP oxidation at 20 ° C

Reaction time M stick OTMP remark H ₂ O / OTMP [wt] H2O2 / OTMP [M] Contents [wt%] conversion [%] 0 0.8 1.8 9.5 75.4 inhomogeneous sample 4 8.7 77.3 inhomogeneous sample 28 3.5 90.9 homogeneous sample 52 1.4 96.2 homogeneous sample

The oxidation of 4-hydroxy-2,2,6,6-tetramethylpiperidine was tested with carbon dioxide alone, but also in the presence of a decomposition inhibitor of hydrogen peroxide, sodium hexametaphosphate. As can be seen from the results of the synthesis of the oxyl, a suitable hydrogen peroxide stabilizer should also be applied at high temperature.

The batch was used as in Examples 1 and 2, the dosing lasted 30 min, the zero sample reacting was identical to the sampling.

The oxidation results are shown in Table 7.

Tab. 7: Oxidation of IITMP at 90 ° C

Marking the experiment Collection time [Min] CO ₂ catalyst [g] hexamethylphosphoric an sodnv [G] Ph S H K r — i A ¹ '8 8 £ stick HTMP ph WITH WITH d § C4 H S £ Ph S H K ΓΊ ¹⁷ O 2 ^ * ν · Η Contents [wt%] conversion [%] HTO-9 ^r 0 2.3 - 0.08 0.8 1.8 8.7 77.3 60 8.8 77.2 HTO-IO 0 3.0 0.5 0.10 0.8 1.8 4.9 87.2 60 1.9 94.9

Industrial usability

The stable free radicals prepared according to the present invention have wide application. They are characterized by a strong inhibitory effect of the polymerization of vinyl monomers, suitable as selective oxidation catalysts of alcohols to aldehydes, excellent antioxidant stabilizers, molecular weight regulators of polymers and the like.

Claims (1)

PATENT CLAIMS Process for preparing 2,2,6,6-tetramethylpiperidine-N-oxyl and its 4-substituted derivatives by catalytic oxidation of the corresponding secondary amine with hydrogen peroxide, optionally in the presence of hydrogen peroxide stabilizers, characterized in that carbon dioxide and the reaction are used as oxidation catalyst. is carried out at a temperature of 20 to 100 ° C.