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Hindered Amine Mechanisms: Part III—Investigations using isotopic labelling
Polymer Degradation and Stability 27 (1990) 65-74
Hindered Amine Mechanisms: Part IIImlnvestigations Using Isotopic Labelling* Peter P. K l e m c h u k , M a t t h e w E. G a n d e & E n z o C o r d o l a CIBA-GEIGY Corporation, Additives Division, Ardsley, New York 10502, USA (Received 6 February 1989; accepted 18 February 1989)
ABSTRACT The literature 'peroxide' mechan&m and our proposed mechanism for the regeneration of hindered amine nitroxyls have been tested with isotopically labelled reactants. Both mechanisms deal with the reaction of alkylperoxy radicals with N-alkyloxy hindered amines, which are products of the reaction of nitroxyl radicals with alkyl radicals. The 'peroxide' mechanism predicts the regeneration of nitroxyl and formation of dialkyl peroxide. Our mechanism predicts the regeneration of nitroxyl and formation of ketones, alcohols and carboxylic acids, depending on the oxidizing substrate. The results of this work confirm the new proposed regeneration mechanism but not the previous 'peroxide' mechanism. The features of the confirmed mechanism are \ \ N O R + R'OO. , NO. + R~-------O+ R'OH / / This basic mechanism is also proposed for a~Tlperoxy radicals \ \ N O R + R'C(O)OO. ~ NO. + R - - O + R'COOH 7 /
INTRODUCTION Recently we published the first paper from an investigation of the mechanisms of action of hindered amine stabilizers. ~ That work consisted of * This paper was presented in part at the Symposium on the Environmental Degradation of Polymers sponsored by the Division of Polymeric Materials: Science and Engineering at the 3rd Chemical Congress of North America held in Toronto, Canada, on 5-10 June, 1988. 65
Polymer Degradation and Stability 0141-3910/89/$03"50 © 1989 Elsevier Science Publishers Ltd, England. Printed in Great Britain
66
Peter P. Klemchuk, Matthew E. Gande, Enzo Cordola
radical trapping studies with various hindered amines in the oxidation of several representative substrates, most notably cyclohexane, tetralin, and lauryl aldehyde. It led to the observation that the activity of hindered amines in trapping alkylperoxy radicals is substrate dependent. The reactivity of hindered amines with tetralinperoxy radicals was slow and led to slow generation of the hindered amine nitroxyl. The reactivity of the hindered amines with cyclohexylperoxy radicals was higher than for tetralinperoxy radicals, and was highest for lauroylperoxy radicals. The findings from the earlier studies led to certain postulates regarding the mechanisms of stabilization by hindered amines. 1'2 Among them are the proposal that the oxidation of hydrocarbon polymers proceeds not only through the usual peroxy radical intermediates but also through acylperoxy radical intermediates. The formation of carboxylic acids in oxidized hydrocarbon polymers is in agreement with that postulate, a Another major postulate from that work proposes that the reaction of alkylperoxy radicals with N-alkyloxy hindered amines does not result in the formation of a peroxide, as often mentioned in the literature, 4 but in the formation of ketone from secondary N-alkyloxy hindered amine substituents and alcohols from the alkylperoxy radicals. The work reported in this paper was carried out with cyclohexane-d 12, N-cyclohexyloxy-dl 1-2,2,6,6tetramethylpiperdin-4-yl benzoate, and oxygen-18 to test our postulated mechanism. The use of these labelled materials in this study has permitted the confirmation of our postulated mechanism for the reaction of alkylperoxy radicals with N-alkyloxy hindered amines.
EXPERIMENTAL
General methods Unless otherwise noted, all materials were used as received. Chlorobenzene was Aldrich HPLC grade. AIBN was recrystallized from methanol and stored at 0°C. Tetralin was distilled and stored under nitrogen at 0°C.
Analyses Gas chromatography was performed on a Perkin Elmer model 8410 chromatograph equipped with an FID detector. Helium was used as the carrier gas, and all packed columns were 5 ft x ~ in. Quantitative analyses for 2,2,6,6-tetramethylpiperidin-4-yl benzoate derivatives were performed on a 5% SP2401 column using tetracosane as either an internal or external standard. It was noticed that when nitroxyl was analyzed, in the presence of
Hindered amine mechanisms: Part 1II
67
AIBN, the parent amine was also detected. A 20% 20M Carbowax column was used to quantify cyclohexanone and cyclohexanol. To separate protoand deutero-cyclohexyl products, a Carbowax 20M, 25m × 0"53mm, capillary column was used. Response factors for the proto-compounds were used for the perdeutero-analogs.
Syntheses Syntheses of non-commercial compounds were performed in CIBAGEIGY research laboratories. These compounds satisfied full spectral and elemental analyses. 2,2,6,6-Tetramethylpiperidin-4-yl benzoate (1) could be prepared from the commercially available 2,2,6,6-tetramethylpiperidin-4-ol. Oxidation of a secondary hindered amine with mCPBA could give either the corresponding hydroxylamine or the nitroxyl (2).5 N-alkoxy derivatives were obtained via photolysis of di-t-butyl peroxide with the corresponding N-oxyl-2,2,6,6-tetramethylpiperidin-4-yl derivative in the appropriate alkane solvent, or through ether formation reactions. 6
AIBN induced oxidation procedure (general procedure) A 10ml chlorobenzene solution, 1.0M in oxidizing substrate and 1 × 10 - 2 N in additive, was charged into a 150ml flat bottom reaction flask equipped with a side arm. The assembly was then connected to a pressure transducer, partially evacuated and flushed with pure oxygen five times, sealed, placed in an oil bath at 60°C, and magnetically stirred. After thermal equilibration (15min), the system was vented to atmospheric pressure, 325 mg (1"98 mmol, 0"2M) AIBN was added, and the system was resealed. While the oxygen pressure was being monitored, aliquots (approximately 1.0 ml) were removed using a syringe and analyzed by either GC alone, or GC/MS.
1-Cyclohexyioxy-2,2,6,6-tetramethylpiperidin-4-yl benzoate (1) inhibited cyclohexane-d t 2 oxidation Using the previous procedure, 964mg (10mmol) cyclohexane-d12 was oxidized in the presence of 35.9 mg (0.10 mmol) (1). The perproto/perdeutero ratios of cyclohexanone and cyclohexanol were determined by GC/MS.
1-Cyclohexyloxy-d 11-2,2,6,6-tetramethyipiperidin'4-Y I benzoate (2) inhibited cyciohexane oxidation The above procedure was modified slightly. Thus to 26.0 mg (0.070 mmol) (2) was added 13 ml ofchlorobenzene containing protocyclohexane (1.0M). To a
68
Peter P. Klemchuk, Matthew E. Gande, Enzo Cordola
150 ml flat bottom flask, equipped with a side arm capped with a rubber septum, was added 10ml of this solution. After attaching to a pressure transducer the system was partially evacuated and flushed with oxygen five times. After thermal equilibration in a 60°C oil bath (15 min), excess pressure was vented and 325 mg (1.98 mmol) AIBN was added via a side arm. While the oxygen pressure was being monitored, aliquots (approximately 1.0 ml) were removed using a syringe and analyzed by VPC. The perproto/ perdeutero ratios of cyclohexanone and cyclohexanol were determined by GC/MS.
1-Cyclohexyloxy-2,2,6,6-tetramethylpiperidin-4-yl cyclohexane ~sO 2 oxidation
benzoate (1) inhibited
To a 50 ml Pyrex reaction tube, equipped with an adapter to attach it to a pressure transducer and a gas line, was added 4.0 ml of a chlorobenzene solution containing cyclohexane (I'0M), (1) (0"01M), and AIBN (0"2M). The system was cooled to - 7 8 ° C and evacuated. Approximately I atm of 180 labelled oxygen gas was added to the closed system and the reaction tube was heated in a 60°C oil bath. After 5 h the tube was removed and the solution analyzed. The labelled product ratios were determined by GC/MS.
Oxidation of cyclohexanol during 1-cyclohexyloxy-dl 1-2,2,6,6-tetramethylpiperidin-4-yl benzoate (2) inhibited cyclohexane-d12 oxidation The general procedure was modified by the addition of 0"0044M protocyclohexanol and the oxygen pressure was not monitored. Conversion of protocyclohexanol to protocyclohexanone was determined by GC analysis.
RESULTS Deuterium-labelled reactants were used in an effort to confirm our proposal for the regeneration mechanism of hindered amine functioning (Scheme 1). The inhibition of cyclohexane-d12 oxidation with N-cyclohexyloxy-2,2,6,6tetramethylpiperidin-4-yl benzoate afforded the analytical results summarized in Table 1. This oxidation, as those reported in our earlier work, was initiated by the thermolysis of 2,2'-azobisisobutyronitrole (AIBN) in chlorobenzene at 60°C. The main products of the inhibited oxidation were cyclohexanone, cyclohexanol, and the hindered amine nitroxyl. Gas Chromatography/Mass Spectrometery analysis of cyclohexanone revealed
Hindered amine mechanisms: Part III
69
+
o.
.o R= O
+
R'OH
R'O-
/ R
SCHEME
1
the ratio of protocyclohexanone to cyclohexanone-dxo to be 1:1-4. The corresponding ratio for cyclohexanol was found to be 0:l.0--i.e. only cyclohexanol-dx 1 was formed. The protocyclohexanone content of the reaction mixture at 5h, 3-1 mmol/litre, when added to the residual cyclohexyloxy hindered amine, 7.1 mmol/litre, gives an amount which is in agreement with the initial concentration of the cyclohexyloxy hindered amine. Thus, all the protocyclohexyloxy hindered amine which was consumed was isolated as unlabelled cyclohexanone. The cyclohexanol-d 11 in the reaction mixture originated from the reaction of cyclohexylperoxy-dll radicals with the hindered amine and from the Russell termination of two cyclohexylperoxy-d~ radicals. Protocyclohexanone originated from the reaction of the cyclohexyloxy hindered amine
TABLE 1 C o n c e n t r a t i o n s of Constituents in the N-Cyclohexyloxy-2,2,6,6-Tetramethylpiperidin-4-yl Benzoate Inhibited Oxidation of Cyclohexane-d12 "'b
Time (h)
Cyclohexanonec
Cyclohexanol d
~NOR
~NO"
~NH
0-0 1'0 2'0 3'0 4"0 5-0
0'0 1'2 3"0 4-6 6'2 7.5
0-0 1-5 3-0 4'2 6.0 6.8
10"5 10.0 9.1 8'5 7.8 7.1
0-0 0-4 0'7 1.1 1.6 1.7
0"0 0.0 0.1 0.2 0.3 0.3
I'0M cyclohexane-d12, 0'010M ~ N O R , chiorobenzene. b All c o n c e n t r a t i o n s in mmol/litre. c H : D = 1.0:1.4 at 5.0h. d H : D = 0"0:l'0 at 5'0h.
0"20M A I B N ,
1 atm
0 2, 60°C,
Peter P. Klemchuk, Matthew E. Gande, Enzo Cordola
70
with either cyclohexylperoxy-d~~ or 2-isobutyronitrile peroxy radicals: /N
+
O"
; /\NO. + ( ~ = O
+~
dll
\ N ~
U,l
+ (CH3)2C(CN)OO"
/
H
/
NO" +
+ (CH3)2C(CN)OH Cyclohexanone-dl0 originated from the Russell termination of cyclohexylperoxy-d,, radicals:
dll
dlo
and from the Russell termination of cyclohexylperoxy-dl, radicals with 2isobutyronitrileperoxy radicals:
~
< ...~==O+ (CH3)2C(CN)OH dlo
OO" + (CH3)2C(CN)OO" dll
When the comparable experiment was carried out with deuterium-labelling in the N-cyclohexyloxysubstituent of the hindered amine the data in Table 2 TABLE 2 Concentrations of Constituents in the N-Cyclohexyloxy-d,,-2,2,6,6-Tetramethylpiperidin-4-yl Benzoate Inhibited Oxidation of Cyclohexane a'b
Time (h)
Cyclohexanone~
Cyclohexanola
~NOR
~NO"
~NH
0'0 0"5 1.0 2.0 3'0 4.0 5'0 6"0
0"0 1'3 2.3 4.1 6"0 7"8 9-7 10"0
0"6 1'7 2.7 3'3 7'9 9-9 11"6 11"3
5'3 5"3 4.7 3"9 3"1 2.7 1"9 1'3
0"0 0'3 0.5 0"9 1.3 1-8 2'5 2'5
0"0 0"0 0.0 0'1 0.2 0'5 0"3 0"5
a I'0M cyclohexane, 0"005M ....NOR, 0-20M AIBN, 1 atm 02, 60°C, chlorobenzene. b All concentrations in mmoi/litre. c H : D = 1"6:1.0 at 6.0h. a H : D = 1'0:0'0 at 6'0h.
Hindered amine mechanisms: Part 1II
71
were obtained. The perproto to perdeutero ratio ofcyclohexanone was 1.6 to 1.0. Only protocyclohexanol was obtained. The sum of the cyclohexanoned~o content of the reaction mixture at 6 h, 3-8 mmol/litre, and the residual Ncyclohexyloxy-d~lhindered amine, 1.3mmol/litre, is in reasonable agreement with the starting quantity of the hindered amine. Thus again, all the Nalkoxy hindered amine which was consumed was isolated as the correctly substituted cyclohexanone, cyclohexanone-d~o, in conformance with our proposed mechanism. The quantity of total cyclohexanone formed in Table 1 is slightly greater than total cyclohexanol. Two possible causes considered for this were the cross-termination reaction with isobutyronitrileperoxy radicals and oxidation ofcyclohexanol under the reaction conditions. While the extent of the former reaction could not be determined, further experiments demonstrated that the latter reaction was occurring. When protocyclohexanol was present during cyclohexane-d12 radical oxidation, inhibited by Ncyclohexyloxy-dlx hindered amine, some of the alcohol was oxidized to protocyclohexanone (Table 3). In a third labelling experiment, this one with an enriched oxygen-18 atmosphere, we studied the location of the isotopic oxygen among the reaction products in the N-cyclohexyloxy-2,2,6,6-tetramethylpiperidin-4-yl benzoate inhibited oxidation ofcyclohexane. As expected for our proposed mechanism (Scheme 1) and as summarized in Table 4, the hindered amine nitroxyl contained only oxygen-18 and the cyclohexanone was a mixture of 75% oxygen-16 and 25% oxygen-18. According to the literature 'peroxide' mechanism the nitroxyl resulting from the reaction of the cyclohexyloxy TABLE 3 Concentrations of Protocyclohexyl Derivatives in the NCyclohexyloxy-d x1-2,2,6,6-Tet ramethylpiperidin-4-yl Benzoate Inhibited Oxidation of Cyclohexane-d 12°'b
Time (h)
Cyclohexanol
Cyclohexanone
0"0 0"5 1"0 2"0 3-0 4"0
4"4 4"1 3"9 3"5 3'2 3"0
0.0 0.3 0.6 0.9 1,2 1"3
a I'0M cyciohexane-d12, 0"010M ~ N O R , 0"2M AIBN, 0-0044M protocyclohexanol, 1 atm 02, 60°C, chlorobenzene. b All concentrations in mmol/litre.
72
Peter P. Klemchuk, Matthew E. Gande, Enzo Cordola
TABLE 4 Ratios of 160 to ~sO in Products from the NCyclohexyloxy-2,2,6,6-tetramethylpiperidinyl Benzoate Inhibited Oxidation of Cyclohexane* Product
Ratio: 160/1sO
Cyclohexanone Cyclohexanol ~NO.
3:1 0:1 0:1
° I'0M cyclohexane, 0"010M~NOR, 0"20MAIBN, 1 atm ~sO2, 5 h reaction. hindered amine derivative should retain the oxygen-16 of the original compound: /~N 1 6 0 ~
_t_ ( ~ -
180--180 •
I,
/\ N ' 6 0 " d- ( ~ - 1 8 0 - - 1 8 ~ Our mechanism predicts oxygen-18 in the nitroxyl and oxygen-16 in the cyclohexanone:
/
\ 180 •
•
/
+
lSOH
No exchange of oxygen was observed when 2,2,6,6-tetramethylpiperidinN-oxyl was stirred under an atmosphere of oxygen-18 for 5 h at 60°C in chlorobenzene with 0"2M AIBN and 1 M cyclohexane.
DISCUSSION The work described in this paper was carried out to try to confirm the mechanism proposed in our earlier paper for the recycling mechanism of hindered amines. Since that mechanism was in disagreement with the mechanism generally accepted in the literature, and attributed to Denisov, it was necessary to establish with care the validity of our proposed mechanism.
Hindered amine mechanisms: Part III
73
That has now been done with the results from labelled reactants reported in this paper. The labelled reactants established unequivocally that the Ncyclohexyloxy substituent was giving rise to cyclohexanone and not dicyclohexyl peroxide as predicted by the literature mechanism. The agreement between the quantity of N-cyclohexyloxy compound consumed and cyclohexanone formed, both perproto- and perdeutero-, is convincing. In both instances the ratio of perproto- to perdeuterocyclohexanone was very close to that predicted by the proposed mechanism and not at all in agreement with the 'peroxide' mechanism, even assuming the decomposition of a dicyclohexylperoxide product into cyclohexanone and cyclohexanol
(vide infra). The results with oxygen-18 are also in complete agreement with the proposed nitroxyl regeneration mechanism and not with the 'peroxide' mechanism. The 'peroxide' mechanism appears to predict that the oxygen of the N-alkyloxy hindered amine is retained by the resulting nitroxyl and atmospheric oxygen enters the peroxide, whereas the instant proposed mechanism predicts the N-alkyloxy oxygen is incorporated into the ketone product (from secondary N-alkyloxy hindered amines) and atmospheric oxygen is incorporated into the nitroxyl and alcohol formed from the alkylperoxy radical. The results of the labelling experiments are not supportive of the 'peroxide' mechanism. That dicyclohexyl peroxide was not being formed in our experiments from the reaction of the N-cyclohexyloxy hindered amine and cyclohexylperoxy radicals was confirmed by the yields and compositions of products in the deuterium-labelled experiments. Should dicyclohexyl peroxide have been formed but have been unstable in our reactions we would have expected scrambling of deuterium labelling (Scheme 2). Since that was not observed, there is no evidence for the formation of dicyclohexyl peroxide in our experiments. The mechanism postulated in Scheme 1 includes a proposed radical cation with an alkoxide counterion. We have no direct proof of this intermediate. OD
0
dl0
0
OH
d~o
SCHEME 2
74
Peter P. Klemchuk, Matthew E. Gande, Enzo Cordola
Evidence for it comes from the reaction products and the related intermediate in the oxidation of alcohols by 2,2,6,6-tetramethylpiperidinyl1-oxyl and m-chloroperbenzoic acid. 7'8 It is important to keep in mind that these results were obtained with essentially one reaction sequence and from solution experiments. They are expected to be applicable to oxidations with other substrates and also to solid polymers but, at present, confirmation in other systems still needs to be achieved. CONCLUSION The results of this study with deuterium-labelled reactants and oxygen-18 confirm the new proposed mechanism for the regeneration of hindered amine nitroxyls. They highlight the fact that products from the functioning of hindered amines as photostabilizers--ketones, alcohols, and carboxylic acids--are relatively innocuous. They are less likely to initiate oxidation than hydroperoxides (produced from stabilization by hindered phenols) and peroxides (proposed products of the 'peroxide' regeneration cycle for nitroxyl). ACKNOWLEDGEMENTS The authors would like to thank Dr R. Ravichandran, Dr J. Galbo and Mr M. Ackerman for synthesizing the hindered amines for this study. Additionally, we would like to thank Mr K. Ng and Mr B. Piatek for their help in identifying the reaction products.
REFERENCES 1. Klemchuk, P. P. & Gande, M. E., Poly. Deg. and Stab., 22 (1988) 241. 2. Klemchuk, P. P. & Gande, M. E., MacromoL Chem., 28 (1984) 117-44. 3. Carlsson, D. J. 9th Annual Conference on Advances in the Stabilization and Controlled Degradation of Polymers, Lucerne, Switzerland, 1987. 4. (a) Shilov, Yu. B., Battalova, R. M. & Denisov, E. T., Dokl. Akad. Nauk, SSSR, 207 (1972) 388; (b) Dagonneua, M., Ivanov, V. B., Rozantsev, E. G., Sholle, V. D. & Kagan, E. S., J M S Rev. Macromol. Chem. Phys., C22 (1983) 169. 5. Toda, T., Mori, E. & Murayama, K., Bull. Chem. Soc. Jap., 45 (1972) 1904. 6. (a) Grattan, D. W., Carlsson, D. J. & Wiles, D. M., Poly. Deg. andStab., 1 (1979) 69; (b) Kurumada, T., Ohsawa, H., Fujita, T. & Toda, T. J., Polym. Sci. Polym. Chem. Ed., 22 (1984) 277. 7. Ganem, B. J., Org. Chem., 40 (1975) 1998. 8. Semmelhack, M. F., Schmid, C. R. & Cortes, D. A., Tetrahedron Lett., 27 (1985} 1119.
Hindered Amine Mechanisms: Part IIImlnvestigations Using Isotopic Labelling* Peter P. K l e m c h u k , M a t t h e w E. G a n d e & E n z o C o r d o l a CIBA-GEIGY Corporation, Additives Division, Ardsley, New York 10502, USA (Received 6 February 1989; accepted 18 February 1989)
ABSTRACT The literature 'peroxide' mechan&m and our proposed mechanism for the regeneration of hindered amine nitroxyls have been tested with isotopically labelled reactants. Both mechanisms deal with the reaction of alkylperoxy radicals with N-alkyloxy hindered amines, which are products of the reaction of nitroxyl radicals with alkyl radicals. The 'peroxide' mechanism predicts the regeneration of nitroxyl and formation of dialkyl peroxide. Our mechanism predicts the regeneration of nitroxyl and formation of ketones, alcohols and carboxylic acids, depending on the oxidizing substrate. The results of this work confirm the new proposed regeneration mechanism but not the previous 'peroxide' mechanism. The features of the confirmed mechanism are \ \ N O R + R'OO. , NO. + R~-------O+ R'OH / / This basic mechanism is also proposed for a~Tlperoxy radicals \ \ N O R + R'C(O)OO. ~ NO. + R - - O + R'COOH 7 /
INTRODUCTION Recently we published the first paper from an investigation of the mechanisms of action of hindered amine stabilizers. ~ That work consisted of * This paper was presented in part at the Symposium on the Environmental Degradation of Polymers sponsored by the Division of Polymeric Materials: Science and Engineering at the 3rd Chemical Congress of North America held in Toronto, Canada, on 5-10 June, 1988. 65
Polymer Degradation and Stability 0141-3910/89/$03"50 © 1989 Elsevier Science Publishers Ltd, England. Printed in Great Britain
66
Peter P. Klemchuk, Matthew E. Gande, Enzo Cordola
radical trapping studies with various hindered amines in the oxidation of several representative substrates, most notably cyclohexane, tetralin, and lauryl aldehyde. It led to the observation that the activity of hindered amines in trapping alkylperoxy radicals is substrate dependent. The reactivity of hindered amines with tetralinperoxy radicals was slow and led to slow generation of the hindered amine nitroxyl. The reactivity of the hindered amines with cyclohexylperoxy radicals was higher than for tetralinperoxy radicals, and was highest for lauroylperoxy radicals. The findings from the earlier studies led to certain postulates regarding the mechanisms of stabilization by hindered amines. 1'2 Among them are the proposal that the oxidation of hydrocarbon polymers proceeds not only through the usual peroxy radical intermediates but also through acylperoxy radical intermediates. The formation of carboxylic acids in oxidized hydrocarbon polymers is in agreement with that postulate, a Another major postulate from that work proposes that the reaction of alkylperoxy radicals with N-alkyloxy hindered amines does not result in the formation of a peroxide, as often mentioned in the literature, 4 but in the formation of ketone from secondary N-alkyloxy hindered amine substituents and alcohols from the alkylperoxy radicals. The work reported in this paper was carried out with cyclohexane-d 12, N-cyclohexyloxy-dl 1-2,2,6,6tetramethylpiperdin-4-yl benzoate, and oxygen-18 to test our postulated mechanism. The use of these labelled materials in this study has permitted the confirmation of our postulated mechanism for the reaction of alkylperoxy radicals with N-alkyloxy hindered amines.
EXPERIMENTAL
General methods Unless otherwise noted, all materials were used as received. Chlorobenzene was Aldrich HPLC grade. AIBN was recrystallized from methanol and stored at 0°C. Tetralin was distilled and stored under nitrogen at 0°C.
Analyses Gas chromatography was performed on a Perkin Elmer model 8410 chromatograph equipped with an FID detector. Helium was used as the carrier gas, and all packed columns were 5 ft x ~ in. Quantitative analyses for 2,2,6,6-tetramethylpiperidin-4-yl benzoate derivatives were performed on a 5% SP2401 column using tetracosane as either an internal or external standard. It was noticed that when nitroxyl was analyzed, in the presence of
Hindered amine mechanisms: Part 1II
67
AIBN, the parent amine was also detected. A 20% 20M Carbowax column was used to quantify cyclohexanone and cyclohexanol. To separate protoand deutero-cyclohexyl products, a Carbowax 20M, 25m × 0"53mm, capillary column was used. Response factors for the proto-compounds were used for the perdeutero-analogs.
Syntheses Syntheses of non-commercial compounds were performed in CIBAGEIGY research laboratories. These compounds satisfied full spectral and elemental analyses. 2,2,6,6-Tetramethylpiperidin-4-yl benzoate (1) could be prepared from the commercially available 2,2,6,6-tetramethylpiperidin-4-ol. Oxidation of a secondary hindered amine with mCPBA could give either the corresponding hydroxylamine or the nitroxyl (2).5 N-alkoxy derivatives were obtained via photolysis of di-t-butyl peroxide with the corresponding N-oxyl-2,2,6,6-tetramethylpiperidin-4-yl derivative in the appropriate alkane solvent, or through ether formation reactions. 6
AIBN induced oxidation procedure (general procedure) A 10ml chlorobenzene solution, 1.0M in oxidizing substrate and 1 × 10 - 2 N in additive, was charged into a 150ml flat bottom reaction flask equipped with a side arm. The assembly was then connected to a pressure transducer, partially evacuated and flushed with pure oxygen five times, sealed, placed in an oil bath at 60°C, and magnetically stirred. After thermal equilibration (15min), the system was vented to atmospheric pressure, 325 mg (1"98 mmol, 0"2M) AIBN was added, and the system was resealed. While the oxygen pressure was being monitored, aliquots (approximately 1.0 ml) were removed using a syringe and analyzed by either GC alone, or GC/MS.
1-Cyclohexyioxy-2,2,6,6-tetramethylpiperidin-4-yl benzoate (1) inhibited cyclohexane-d t 2 oxidation Using the previous procedure, 964mg (10mmol) cyclohexane-d12 was oxidized in the presence of 35.9 mg (0.10 mmol) (1). The perproto/perdeutero ratios of cyclohexanone and cyclohexanol were determined by GC/MS.
1-Cyclohexyloxy-d 11-2,2,6,6-tetramethyipiperidin'4-Y I benzoate (2) inhibited cyciohexane oxidation The above procedure was modified slightly. Thus to 26.0 mg (0.070 mmol) (2) was added 13 ml ofchlorobenzene containing protocyclohexane (1.0M). To a
68
Peter P. Klemchuk, Matthew E. Gande, Enzo Cordola
150 ml flat bottom flask, equipped with a side arm capped with a rubber septum, was added 10ml of this solution. After attaching to a pressure transducer the system was partially evacuated and flushed with oxygen five times. After thermal equilibration in a 60°C oil bath (15 min), excess pressure was vented and 325 mg (1.98 mmol) AIBN was added via a side arm. While the oxygen pressure was being monitored, aliquots (approximately 1.0 ml) were removed using a syringe and analyzed by VPC. The perproto/ perdeutero ratios of cyclohexanone and cyclohexanol were determined by GC/MS.
1-Cyclohexyloxy-2,2,6,6-tetramethylpiperidin-4-yl cyclohexane ~sO 2 oxidation
benzoate (1) inhibited
To a 50 ml Pyrex reaction tube, equipped with an adapter to attach it to a pressure transducer and a gas line, was added 4.0 ml of a chlorobenzene solution containing cyclohexane (I'0M), (1) (0"01M), and AIBN (0"2M). The system was cooled to - 7 8 ° C and evacuated. Approximately I atm of 180 labelled oxygen gas was added to the closed system and the reaction tube was heated in a 60°C oil bath. After 5 h the tube was removed and the solution analyzed. The labelled product ratios were determined by GC/MS.
Oxidation of cyclohexanol during 1-cyclohexyloxy-dl 1-2,2,6,6-tetramethylpiperidin-4-yl benzoate (2) inhibited cyclohexane-d12 oxidation The general procedure was modified by the addition of 0"0044M protocyclohexanol and the oxygen pressure was not monitored. Conversion of protocyclohexanol to protocyclohexanone was determined by GC analysis.
RESULTS Deuterium-labelled reactants were used in an effort to confirm our proposal for the regeneration mechanism of hindered amine functioning (Scheme 1). The inhibition of cyclohexane-d12 oxidation with N-cyclohexyloxy-2,2,6,6tetramethylpiperidin-4-yl benzoate afforded the analytical results summarized in Table 1. This oxidation, as those reported in our earlier work, was initiated by the thermolysis of 2,2'-azobisisobutyronitrole (AIBN) in chlorobenzene at 60°C. The main products of the inhibited oxidation were cyclohexanone, cyclohexanol, and the hindered amine nitroxyl. Gas Chromatography/Mass Spectrometery analysis of cyclohexanone revealed
Hindered amine mechanisms: Part III
69
+
o.
.o R= O
+
R'OH
R'O-
/ R
SCHEME
1
the ratio of protocyclohexanone to cyclohexanone-dxo to be 1:1-4. The corresponding ratio for cyclohexanol was found to be 0:l.0--i.e. only cyclohexanol-dx 1 was formed. The protocyclohexanone content of the reaction mixture at 5h, 3-1 mmol/litre, when added to the residual cyclohexyloxy hindered amine, 7.1 mmol/litre, gives an amount which is in agreement with the initial concentration of the cyclohexyloxy hindered amine. Thus, all the protocyclohexyloxy hindered amine which was consumed was isolated as unlabelled cyclohexanone. The cyclohexanol-d 11 in the reaction mixture originated from the reaction of cyclohexylperoxy-dll radicals with the hindered amine and from the Russell termination of two cyclohexylperoxy-d~ radicals. Protocyclohexanone originated from the reaction of the cyclohexyloxy hindered amine
TABLE 1 C o n c e n t r a t i o n s of Constituents in the N-Cyclohexyloxy-2,2,6,6-Tetramethylpiperidin-4-yl Benzoate Inhibited Oxidation of Cyclohexane-d12 "'b
Time (h)
Cyclohexanonec
Cyclohexanol d
~NOR
~NO"
~NH
0-0 1'0 2'0 3'0 4"0 5-0
0'0 1'2 3"0 4-6 6'2 7.5
0-0 1-5 3-0 4'2 6.0 6.8
10"5 10.0 9.1 8'5 7.8 7.1
0-0 0-4 0'7 1.1 1.6 1.7
0"0 0.0 0.1 0.2 0.3 0.3
I'0M cyclohexane-d12, 0'010M ~ N O R , chiorobenzene. b All c o n c e n t r a t i o n s in mmol/litre. c H : D = 1.0:1.4 at 5.0h. d H : D = 0"0:l'0 at 5'0h.
0"20M A I B N ,
1 atm
0 2, 60°C,
Peter P. Klemchuk, Matthew E. Gande, Enzo Cordola
70
with either cyclohexylperoxy-d~~ or 2-isobutyronitrile peroxy radicals: /N
+
O"
; /\NO. + ( ~ = O
+~
dll
\ N ~
U,l
+ (CH3)2C(CN)OO"
/
H
/
NO" +
+ (CH3)2C(CN)OH Cyclohexanone-dl0 originated from the Russell termination of cyclohexylperoxy-d,, radicals:
dll
dlo
and from the Russell termination of cyclohexylperoxy-dl, radicals with 2isobutyronitrileperoxy radicals:
~
< ...~==O+ (CH3)2C(CN)OH dlo
OO" + (CH3)2C(CN)OO" dll
When the comparable experiment was carried out with deuterium-labelling in the N-cyclohexyloxysubstituent of the hindered amine the data in Table 2 TABLE 2 Concentrations of Constituents in the N-Cyclohexyloxy-d,,-2,2,6,6-Tetramethylpiperidin-4-yl Benzoate Inhibited Oxidation of Cyclohexane a'b
Time (h)
Cyclohexanone~
Cyclohexanola
~NOR
~NO"
~NH
0'0 0"5 1.0 2.0 3'0 4.0 5'0 6"0
0"0 1'3 2.3 4.1 6"0 7"8 9-7 10"0
0"6 1'7 2.7 3'3 7'9 9-9 11"6 11"3
5'3 5"3 4.7 3"9 3"1 2.7 1"9 1'3
0"0 0'3 0.5 0"9 1.3 1-8 2'5 2'5
0"0 0"0 0.0 0'1 0.2 0'5 0"3 0"5
a I'0M cyclohexane, 0"005M ....NOR, 0-20M AIBN, 1 atm 02, 60°C, chlorobenzene. b All concentrations in mmoi/litre. c H : D = 1"6:1.0 at 6.0h. a H : D = 1'0:0'0 at 6'0h.
Hindered amine mechanisms: Part 1II
71
were obtained. The perproto to perdeutero ratio ofcyclohexanone was 1.6 to 1.0. Only protocyclohexanol was obtained. The sum of the cyclohexanoned~o content of the reaction mixture at 6 h, 3-8 mmol/litre, and the residual Ncyclohexyloxy-d~lhindered amine, 1.3mmol/litre, is in reasonable agreement with the starting quantity of the hindered amine. Thus again, all the Nalkoxy hindered amine which was consumed was isolated as the correctly substituted cyclohexanone, cyclohexanone-d~o, in conformance with our proposed mechanism. The quantity of total cyclohexanone formed in Table 1 is slightly greater than total cyclohexanol. Two possible causes considered for this were the cross-termination reaction with isobutyronitrileperoxy radicals and oxidation ofcyclohexanol under the reaction conditions. While the extent of the former reaction could not be determined, further experiments demonstrated that the latter reaction was occurring. When protocyclohexanol was present during cyclohexane-d12 radical oxidation, inhibited by Ncyclohexyloxy-dlx hindered amine, some of the alcohol was oxidized to protocyclohexanone (Table 3). In a third labelling experiment, this one with an enriched oxygen-18 atmosphere, we studied the location of the isotopic oxygen among the reaction products in the N-cyclohexyloxy-2,2,6,6-tetramethylpiperidin-4-yl benzoate inhibited oxidation ofcyclohexane. As expected for our proposed mechanism (Scheme 1) and as summarized in Table 4, the hindered amine nitroxyl contained only oxygen-18 and the cyclohexanone was a mixture of 75% oxygen-16 and 25% oxygen-18. According to the literature 'peroxide' mechanism the nitroxyl resulting from the reaction of the cyclohexyloxy TABLE 3 Concentrations of Protocyclohexyl Derivatives in the NCyclohexyloxy-d x1-2,2,6,6-Tet ramethylpiperidin-4-yl Benzoate Inhibited Oxidation of Cyclohexane-d 12°'b
Time (h)
Cyclohexanol
Cyclohexanone
0"0 0"5 1"0 2"0 3-0 4"0
4"4 4"1 3"9 3"5 3'2 3"0
0.0 0.3 0.6 0.9 1,2 1"3
a I'0M cyciohexane-d12, 0"010M ~ N O R , 0"2M AIBN, 0-0044M protocyclohexanol, 1 atm 02, 60°C, chlorobenzene. b All concentrations in mmol/litre.
72
Peter P. Klemchuk, Matthew E. Gande, Enzo Cordola
TABLE 4 Ratios of 160 to ~sO in Products from the NCyclohexyloxy-2,2,6,6-tetramethylpiperidinyl Benzoate Inhibited Oxidation of Cyclohexane* Product
Ratio: 160/1sO
Cyclohexanone Cyclohexanol ~NO.
3:1 0:1 0:1
° I'0M cyclohexane, 0"010M~NOR, 0"20MAIBN, 1 atm ~sO2, 5 h reaction. hindered amine derivative should retain the oxygen-16 of the original compound: /~N 1 6 0 ~
_t_ ( ~ -
180--180 •
I,
/\ N ' 6 0 " d- ( ~ - 1 8 0 - - 1 8 ~ Our mechanism predicts oxygen-18 in the nitroxyl and oxygen-16 in the cyclohexanone:
/
\ 180 •
•
/
+
lSOH
No exchange of oxygen was observed when 2,2,6,6-tetramethylpiperidinN-oxyl was stirred under an atmosphere of oxygen-18 for 5 h at 60°C in chlorobenzene with 0"2M AIBN and 1 M cyclohexane.
DISCUSSION The work described in this paper was carried out to try to confirm the mechanism proposed in our earlier paper for the recycling mechanism of hindered amines. Since that mechanism was in disagreement with the mechanism generally accepted in the literature, and attributed to Denisov, it was necessary to establish with care the validity of our proposed mechanism.
Hindered amine mechanisms: Part III
73
That has now been done with the results from labelled reactants reported in this paper. The labelled reactants established unequivocally that the Ncyclohexyloxy substituent was giving rise to cyclohexanone and not dicyclohexyl peroxide as predicted by the literature mechanism. The agreement between the quantity of N-cyclohexyloxy compound consumed and cyclohexanone formed, both perproto- and perdeutero-, is convincing. In both instances the ratio of perproto- to perdeuterocyclohexanone was very close to that predicted by the proposed mechanism and not at all in agreement with the 'peroxide' mechanism, even assuming the decomposition of a dicyclohexylperoxide product into cyclohexanone and cyclohexanol
(vide infra). The results with oxygen-18 are also in complete agreement with the proposed nitroxyl regeneration mechanism and not with the 'peroxide' mechanism. The 'peroxide' mechanism appears to predict that the oxygen of the N-alkyloxy hindered amine is retained by the resulting nitroxyl and atmospheric oxygen enters the peroxide, whereas the instant proposed mechanism predicts the N-alkyloxy oxygen is incorporated into the ketone product (from secondary N-alkyloxy hindered amines) and atmospheric oxygen is incorporated into the nitroxyl and alcohol formed from the alkylperoxy radical. The results of the labelling experiments are not supportive of the 'peroxide' mechanism. That dicyclohexyl peroxide was not being formed in our experiments from the reaction of the N-cyclohexyloxy hindered amine and cyclohexylperoxy radicals was confirmed by the yields and compositions of products in the deuterium-labelled experiments. Should dicyclohexyl peroxide have been formed but have been unstable in our reactions we would have expected scrambling of deuterium labelling (Scheme 2). Since that was not observed, there is no evidence for the formation of dicyclohexyl peroxide in our experiments. The mechanism postulated in Scheme 1 includes a proposed radical cation with an alkoxide counterion. We have no direct proof of this intermediate. OD
0
dl0
0
OH
d~o
SCHEME 2
74
Peter P. Klemchuk, Matthew E. Gande, Enzo Cordola
Evidence for it comes from the reaction products and the related intermediate in the oxidation of alcohols by 2,2,6,6-tetramethylpiperidinyl1-oxyl and m-chloroperbenzoic acid. 7'8 It is important to keep in mind that these results were obtained with essentially one reaction sequence and from solution experiments. They are expected to be applicable to oxidations with other substrates and also to solid polymers but, at present, confirmation in other systems still needs to be achieved. CONCLUSION The results of this study with deuterium-labelled reactants and oxygen-18 confirm the new proposed mechanism for the regeneration of hindered amine nitroxyls. They highlight the fact that products from the functioning of hindered amines as photostabilizers--ketones, alcohols, and carboxylic acids--are relatively innocuous. They are less likely to initiate oxidation than hydroperoxides (produced from stabilization by hindered phenols) and peroxides (proposed products of the 'peroxide' regeneration cycle for nitroxyl). ACKNOWLEDGEMENTS The authors would like to thank Dr R. Ravichandran, Dr J. Galbo and Mr M. Ackerman for synthesizing the hindered amines for this study. Additionally, we would like to thank Mr K. Ng and Mr B. Piatek for their help in identifying the reaction products.
REFERENCES 1. Klemchuk, P. P. & Gande, M. E., Poly. Deg. and Stab., 22 (1988) 241. 2. Klemchuk, P. P. & Gande, M. E., MacromoL Chem., 28 (1984) 117-44. 3. Carlsson, D. J. 9th Annual Conference on Advances in the Stabilization and Controlled Degradation of Polymers, Lucerne, Switzerland, 1987. 4. (a) Shilov, Yu. B., Battalova, R. M. & Denisov, E. T., Dokl. Akad. Nauk, SSSR, 207 (1972) 388; (b) Dagonneua, M., Ivanov, V. B., Rozantsev, E. G., Sholle, V. D. & Kagan, E. S., J M S Rev. Macromol. Chem. Phys., C22 (1983) 169. 5. Toda, T., Mori, E. & Murayama, K., Bull. Chem. Soc. Jap., 45 (1972) 1904. 6. (a) Grattan, D. W., Carlsson, D. J. & Wiles, D. M., Poly. Deg. andStab., 1 (1979) 69; (b) Kurumada, T., Ohsawa, H., Fujita, T. & Toda, T. J., Polym. Sci. Polym. Chem. Ed., 22 (1984) 277. 7. Ganem, B. J., Org. Chem., 40 (1975) 1998. 8. Semmelhack, M. F., Schmid, C. R. & Cortes, D. A., Tetrahedron Lett., 27 (1985} 1119.