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Synthesis of tritium labelled monomers and polymers
Eur. Polym. J. Vol. 20, No. 4, pp. 343 347, 1984 Printed in Great Britain. All rights reserved
0014-3057/84 $3.00 + 0.00 Copyright ~ 1984 Pergamon Press Ltd
SYNTHESIS OF TRITIUM LABELLED MONOMERS AND POLYMERS* D. R. BURFIELDand C. M. SAVARIAR Department of Chemistry, University of Malaya, Kuala Lumpur 22-1 l, Malaysia (Received 15 July 1983)
Abstract--The use of P205 for promoting the tritiation of various monomers and polymers has been investigated. Methyl methacrylate and vinyl acetate may be labelled at ambient temperatures by this procedure which is also applicable to labelling polystyrene and poly(~t-methylstyrene).Exchange labelling of polymer substrates is most conveniently carried out in chlorinated hydrocarbons. The rate of tritium exchange increases with solvent polarity and temperature. Monomers of high radiochemical purity may be derived from the thermal depolymerization of tritiated polystyrene, poly(~t-methylstyrene) and poly(methyl methacrylate).
INTRODUCTION Radiolabelled monomers assume importance not only in the synthesis of the corresponding labelled homopolymer but also in the investigation of copolymerization systems. The latter application is highlighted in studies where the copolymers are not amenable to simple spectroscopic or chemical analyses [1,2] or where the co- or ter-monomer is presented only in trace quantities [3]. Labelled polymers in turn have been utilised as standards or calibrants for radiochemical, molecular weight and spectroscopic assay, as well as in a variety of miscellaneous studies. However, the widespread application of such radiotracer methods has been hampered by the limited availability and high cost of labelled monomers. These difficulties are compounded by the chemical instability of certain monomers, notably styrene and its derivatives, which further restricts the shelf-life of and hence ready access to these compounds. The cited constraints provide incentives to develop syntheses of labelled monomers and polymers which can be easily carried out by the individual researcher from readily available low cost starting materials and it is with this problem that this publication is concerned. Tritium represents perhaps the ideal isotope for the above purpose as it is readily and cheaply available at high specific activities (5 Ci/g), is relatively safe (flmax = 0.0186 MeV), has a useful half-life (12.35 y) and may be simply incorporated into a wide variety of organic materials [4]. The suitability of this isotope is further enhanced if consideration is given to aspects such as ease of handling as labelled water and the straightforward assay of the labelled product by liquid scintillation counting. Although tritiation of organic compounds can be effected by a wide variety of methods such as Wilzbach tritium gas exposure, catalytic exchange, or
direct chemical synthesis, many of the methods are not suitable for small scale preparation and require specialised handling techniques or equipment not generally available outside radiochemical centres. The most promising routes to tritium labelled monomers for the average bench chemist are a direct chemical synthesis or an exchange reaction involving labelled water as the source of tritium. Thus styrene labelled in the side-chain has been variously prepared by interaction of tritiated water with styryl magnesium bromide [5]; THF
PhCBr=CH 2 + Mg
, PhCMgBr=CH2 THO
PhCT=CH2
or by catalytic reduction of acetophenone [6] or phenylacetylene [4] with tritium gas: PhCOOCH3 + T2
Pt
, PhCT--CH3
I
OT THO
PHC~---CH + T2
Pa/C
,
, PhCTICH2
PhCT = C H T
Dio×ane
Similarly, tritiated alkyl methacrylates have been derived from the corresponding methacrylic acid through the intermediacy of tritium exchange with labelled water followed by alkylation with diazomethane [7]: CH3
I
CH3
I
CH2=CCO2H + TH°-*CH2=CCO2T CH3
*Presented in part at the 26th IUPAC Conference on Macromolecules, Mainz, 1979. 343
CH2N2 ' CH2~CCO2CH2T
344
D.R. BURF|ELDand C. M. SAVARIAR
or by esterification with the appropriate tritium labelled alcohol [8]:
tation and subsequently purified by repetitive reprecipitation to a constant level of activity.
CH3
CH 3
Polymerization
I
I
Polymers of styrene, vinyl acetate and methyl methacrylate were prepared in benzene solution using benzoyl peroxide as initiator at 60°. Poly(~-methylstyrene) was prepared by sulphuric acid catalysed polymerization in dichloromethane at -78°; poly(4-methyl-l-pentene) was synthesised at 30° with Ziegler-Natta catalyst (VC13/AliBu3) in benzene [12].
CH2 ~---CCO2H + CH2TOH--~ CH2 =CCO2CH2T Again, tritiated vinyl acetate has been synthesised by the catalytic addition of acetic acid, which can also be tritiated on the carboxyl group, to tritium labelled acetylene as illustrated below [9]:
Depolymerization
CaC2 + T H O - - ~ C T ~ C H CH3CO2T
, C T 2= C H C O 2 C H
3
Recently labelled methylvinylketone has been efficiently and simply prepared by base catalysed exchange of the monomer with tritiated water [2]: CH2=CHCOCH3 + THO
K2co3 CH2=CHCOCH2T
Tritiated polymers such as those of methyl methacrylate, n-butyl methacrylate, styrene and vinyl acetate have almost invariably been obtained by polymerization of the respective m o n o m e r although preparation of tritiated polystyrene through Wilzbach labelling has been reported [10]. This paper describes the preparation of a variety of important tritiated monomers and polymers by application of a catalysed tritium exchange reaction between tritiated water and the preformed substrate in the presence of an appropriate catalyst. In addition certain reactive monomers have been prepared by the thermal degradation of the labelled parent polymer. All the techniques employed are restricted to those commonly encountered in the chemical laboratory.
Polymers were thermally degraded by rapid heating to about 400° under vacuum (ca. 10-~-10 -2 mmHg), the volatile products being distilled directly into a receiver cooled with dry-ice. Although a variety of degradation set ups were tried, the best monomer yields (>70%) resulted from the simplest system where the polymer (5-10 g) was heated in a 100 ml round bottom flask over a hot bunsen flame. The volatiles were taken off through a very short distillation head directly into the cooled trap.
Radiochemical purity The radiochemical purity of a labelled monomer was determined by the derivative method where the monomer was polymerized and assayed together with the purified polymer. The radiochemical purity is then given by the expression: ~o Radiochemical purity = Specific activity of polymer (dpm/g) x 100 Specific activity of monomer (dpm/g)
Tritium assay Monomers and polymers were assayed as solutions or gels in a toluene based cocktail containing PPO (4 g/l) and POPOP (0.4 g/I). Counting efficiencies were determined by channels ratio and internal standardization. Details of the assay are discussed more fully elsewhere [13]. RESULTS AND DISCUSSION
Monomer labelling by direct catalytic exchange EXPERIMENTAL
Materials Monomers and solvents of reagent grade quality were purified by standard procedures and dried over activated 3A molecular sieves [11]. Polymers and catalysts were commercial samples of at least 99% purity and were used without further purification. Tritiated water (5 Ci/ml) was obtained from the Radiochemical Centre, Amersham and was diluted with inactive distilled water to an activity of 54 mCi/ml.
Monomer labelling Labelling was carried out by stirring together monomer, solvent, catalyst and tritiated water at ambient temperatures (26-30°). Proportions, catalyst and reaction times are indicated in the text. After exchange, the labelled monomers were decanted off the catalyst residues, washed with several portions of water, dried, distilled and stored over 3A molecular sieves. Certain monomers of low radiochemical purity were further purified by fractionation using a 1 m column packed with glass helices.
Polymer exchange Tritiation was carried out by stirring together catalyst, labelled water and a 10% w/v solution of polymer in dichloromethane under the conditions specified in the text. After exchange, the polymers were isolated by methanol precipi-
Acidic catalysts are known to be effective in the labelling of aromatic and occasionally aliphatic compounds. In particular the efficiency of representative catalysts such as sulphuric acid, phosphoric acid, phosphoric acid-boron trifluoride complex, and aluminium chloride are well documented [4]. Recently we have found that phosphorous pentoxide (P205) alone is a useful exchange catalyst for certain classes of organic compounds. The results of tritium exchange of several monomers with P205 are summarized in Table 1. At ambient temperatures, P205 was found to be a useful catalyst for tritiation of 4-methyl-l-pentene and vinyl acetate to significant levels of incorporation and methyl methacrylate and n-butyl methacrylate to lesser extents. It is clear that P205 is not appropriate for highly acid sensitive monomers such as isoprene, styrene and ~-methylstyrene which undergo vigorous polymerization on contact with the catalyst, presumably via a cationic mechanism. An attempt to label ~-methylstyrene above its ceiling temperature (61 °) also resulted in the monomer forming polymeric products on cooling. This problem could conceivably have been circumvented by distillation of the ~-methylstyrene from the catalyst before cooling.
Tritium labelled monomers and polymers Table I. Direct labellingof monomersvia catalytic exchange Tritiated Volume water CH2CI2 P20~ Time % (ml) (/1Ci) (ml) (g) (day) Incorporation 100 2200t 100 2.5 7 1.7
Monomer Methyl methacrylate
345
Radiochemical purity (O/o) 99.3
Styrene 20 20 0.4 * .~-Methylstyrene 20 20 0.4 * Vinyl acetate 50 1600+ -1.3 I 5 85 n-Butyl methacrylate 4 2.4~: -0.09 1 0.6 nd 4-methyl-l-pentene 20 81+ -0.5 7 35 2 Isoprene 10 --0.2 * T = 28h *Monomerpolymerizedrapidly on contact with catalyst, tSpecific activity40 mCi/ml. :~Specificactivity 0.22mCi,'ml.
Although the successfully labelled monomers were all shown to be substantially chemically pure (b.p., GLC, NMR), the radiochemical purities as determined by polymer derivative analysis were extremely variable. Thus, whereas the radiochemical purity of the tritiated methyl methacrylate is excellent, the purities of vinyl acetate and in particularly 4-methyl-l-pentene were low even after careful fractionation. In the latter case, it seems likely that the exchange reaction was accompanied by isomerization of the olefin to give internal olefins of closely similar physical properties but with little or no polymerization activity, e.g.
=k__
*r"
o
\ ~-H ~
T--L_
-5The tritium distribution in vinyl acetate was investigated by hydrolysis of the poly(vinyl acetate) with methanolic potassium hydroxide, and assay of the resultant polymer.
-[-CH2--CH~
KOH/CH3OH• _[_CH2__CH_]7~
I
I
OCCH 3
OH
PI
0
The poly(vinyl alcohol) retained 53% of the tritium showing that the label was fairly uniformly distributed between the main chain and pendant groups. It is apparent that P205 has potential as an exchange catalyst for alkyl methacrylate and vinyl acetate monomers. Almost certainly tritium incorporation could be increased by the use of elevated temperatures vide injka, althouth this may be accompanied by reduced radiochemical purities.
Polymer labelling by direct catalytic exchange Apart from some recently reported results [14] wherein poly(olefins) and polystyrene were labelled
through the intermediacy of chloroaluminium compounds and a much earlier synthesis of tritiated polystyrene by the Wilzbach technique [10], there appears to be no previous attempts to prepare tritium labelled polymers directly. In this study exchange labelling of polystyrene, poly(a-methylstyrene) and poly(methyl methacrylate) using P205 as catalyst was investigated. Polystyrene labelling was studied most extensively and used as a basis to probe the effects of solvent type, temperature, reaction time and catalyst on tritiation efficiency.
Effect of solvent type on tritium exchange Solvents appropriate for polymer exchange reactions are limited to those which not only dissolve the polymeric substrate but also neither poison the exchange catalyst nor readily undergo proton exchange. The only common solvents which adequately meet these requirements proved to be chlorinated hydrocarbons. Solvents such as THF or dioxane, whilst readily solubilising the polymer, completely inhibited the exchange reaction presumably by complexing the acidic intermediates. Examination of a series of chlorinated solvents under standardised conditions revealed that the rate of exchange was dependent on the solvent polarity (Table 2). The exchange rate was found to increase in step with the dielectric constant of the solvent, the exchange being most rapid for dichloromethane (e = 8.9). This observation is fully consistent with the likely polar nature of the reaction intermediates.
Dependence of exchange activity on catalyst type The efficacy of a variety of mineral and Lewis acids in catalysing labelling of polystyrene was investigated. Sulphuric and phosphoric acids proved to be very much inferior to P205 which however was significantly surpassed by A1C13 (Table 3). The activity of AIC13 is consistent with the known activity of chloroaluminium compounds in promoting rapid exchange with aromatic protons [15, 16]. The marked difference in catalytic activity between P205 and phosphoric acid is informative, since it suggests that P205 is not simply a precursor of the phosphoric acid which then subsequently enacts the exchange. Elsewhere [17], in studies of desiccant efficiency in solvent drying, it was shown that labelled water was very rapidly removed from the bulk of the solvent by treatment with 5~ w/v P205. Furthermore, the absence of residual tritium in the solvent phase precluded the possible emergence of phosphoric acid from the desiccant surface into the solvent bulk.
346
D . R . BURFIELD and C. M. SAVARIAR
CI
\ /
Table 2. Tritium exchange labelling of polystyrene in various solvents Specific activity Dielectric of polystyrene Solvent constant (dpm/g) H C~C
/ \
2.1
8.0 × 10 4
H C1 CCI4 2.2 7.3 x 104 CHCI~CCI 2 3.4 12.9 x 104 CHCI3 4.8 21.0 x 104 CH2CI2 8.9 29.4 x 104 Dioxane 2.2 nil Tetrahydrofuran 7.6 nil N,N-dimethylformamide 36.7 nil Reaction conditions 1 g polystyrene; 20 ml solvent; 0.3 g P205; 1.1/~Ci THO (sp. act. 0.22 mCi/ml); T = 28'; reaction time = 24 hr.
Table 3. Dependence of exchange efficiency on catalyst type Tritiated Specific Polystyrene water % activity Catalyst (g) Solvent (/zCi) Incorporation (dpm/g) 88% H3PO4 0,5 CH2CI2 396t <0.001 8.2 x 103 (0.1 g) (10 ml) H2SO4 0.4 CH2CI2 0.55:~ nd nd (0.2 g) (10 ml) AIC13 0.5 CCI4 0.552 19 4.7 x 103 (0.1 g) (10 ml) P205 2,0 CCI4 2.25 2.9 7.3 × 104 (0.6 g) (50 ml) P205 2.0 CC14 2.2+ 12" (0.6 g) (50 ml) Conditions: temperature = 28°; reaction time = 24 hr. *Incorporation after 3 hr at 80°C. ]'Specific activity 40 mCi/ml. $Specific activity 0.22 mCi/ml.
Consequently it m u s t be concluded t h a t the exchange activity o f the P205 catalyst is limited to its surface on which the tritiated water is adsorbed.
Time dependence of exchange reaction The progressive i n c o r p o r a t i o n o f tritium into a polystyrene substrate was m o n i t o r e d over a period of days at r o o m t e m p e r a t u r e whilst employing P205 as catalyst. T h e results (Fig. 1) show t h a t the extent o f exchange is time dependent, the rate of exchange being approximately c o n s t a n t over the investigated period. This progressive exchange contrasts sharply with the k n o w n rapid but short-lived tritium exchange p r o m o t e d by o r g a n o a l u m i n i u m dichlorides [16], underlining a significant difference in mechanism.
acrylate) however showed no significant exchange even after refluxing for several hours. The facile labelling o f the two a r o m a t i c polymers is consistent with the k n o w n lability of the ring p r o t o n s to acid catalysts. The inertness o f poly(methyl methacrylate) reflects the absence of any readily exchangeable protons a n d possible interference by heteroatoms. In general, P205 is a useful catalyst since, unlike H204 or AICI 3 it does not lead to direct chemical interaction with and hence possible modification of the polymer substrate.
12 lO
Temperature dependence of exchange reaction R a p i d exchange reactions are useful from a preparative viewpoint as they reduce the time required for the synthesis. Elevated temperatures n o r m a l l y enhance the exchange activity a n d such is seen to be the case with polystyrene labelling (Table 3). Carrying out the exchange reaction in c a r b o n tetrachloride u n d e r reflux ( ~ 80 °) is seen to increase the tritiation rate by a factor of a b o u t 33 c o m p a r e d to exchange at a m b i e n t temperatures.
Labelling of polymer substrates P205 was f o u n d to be effective as a catalyst for tritiation o f polystyrene and poly(ct-methylstyrene) u n d e r mild conditions (Table 4). Poly(methyl meth-
g
8
~6 ,,o
/
2
{}{•
I
2
I
I
I
4 6 8 Time/days
I
10
Fig. 1. Tritiation of polystyrene as a function of time. Reaction conditions: 2.5 g polymer in 50ml CCI4; 0.8 g P205; 10 pl THO (2.2 #Ci); temperature = 28%
Tritium labelled monomers and polymers
347
Table 4. Direct labelling of polymers and indirect monomer synthesis via polymer degradation
Polymer Polystyrene
Mass (g) 2
Tritiated water (# Ci) 2.2*
5
1100t
12.8
595t
Polystyrene Poly(~-methylstyrene)
Solvent CCI4 (50 ml) CH2CI2 (50 ml) CH2CI2 (100 ml)
Catalyst P20~ (0.6 g) AICI3 (1.0 g) P205 (2.1 g)
Time (day) l 1 1
Radiochemical purity of ~o derived monomer§ Incorporation (~,,i) 2.9 --50 3.9
95 100.1
Poly(methyl 0.5 0.55* CH2CI2 P205 7 nd methacrylate) (10 ml) (0.15 g) -101.4 Poly(methyl Methacrylate)~ Exchange temperature = 28°: *Specificactivity0.22 mCi/ml, tSpecificactivity40 mCi/ml. ,+Labelledpolymerderived from tritiated monomer. §Monomers derived in at least 70~oyield by thermal depolymerization at 400".
Labelled monomer synthesis through polymer polymerization
de-
Certain polymers, notably those derived from ~,ct-disubstituted olefins such as ~-methylstyrene, undergo facile depolymerization at elevated temperatures with almost quantitative yield of monomer.
H2C L
~ n CH2=C /
REFERENCES
\
Ph
.
exchange reactions in both monomeric and polymeric substrates. Tritium labelled monomers such as methyl methacrylate and vinyl acetate and tritiated polymers of styrene and ~t-methylstyrene may be readily synthesised by such procedures. Labelled monomers may also be obtained by thermal depolymerization of tritiated polymers of styrene, ct-methylstyrene and methyl methacrylate.
Ph
Pyrolysis of tritium labelled polymers should thus lead to the corresponding labelled monomer. This was indeed found to be the case and good yields of labelled styrene and a-methylstyrene were obtained from their parent polymers on depolymerization at temperatures around 400 ° (Table 4). Thus although direct catalytic exchange is prohibited under the conditions employed, the labelled monomers can be readily obtained by degradation of the tritiated polymer. The resulting ~t-methylstyrene is effectively radiochemically pure but the tritiated styrene had a somewhat lower purity of 94~. This difference reflects the relative cleanness of the depolymerization since polystyrene degradation is known to be accompanied by byproducts such as toluene and styrene dimers [18]. Polymer depolymerization is also appropriate to alkyl methacrylate polymers. Thus, for example, m o n o m e r yield and radiochemical purity of methyl methacrylate are found to be high (Table 4). This is of some interest as although poly(methymethacrylate) is not readily labelled by the investigated procedures, alkyl methacrylate polymers with 3H- or '4C-labels are readily and cheaply available commercially whereas their respective monomers are not. CONCLUSION Reagent grade P205 may be used to catalyse tritium
1. G. Ayrey, Adv. Polym. Sci. 6, 142 (1969). 2. D. R. Burfield and C. M. Savariar, Eur. Polym J. 16, 1003 (1980). 3. D. R. Burfield and C. M. Savariar, J. Polym. Sci., Polym. Lett. Ed. 20, 515 (1982). 4. E. A. Evans, Tritium and its Compounds 2nd edn. Butterworths, London (1974). 5. W. A. Pryor, R. W. Henderson, R. A. Patsiga and N. Caroll, J. Am. chem. Soc. 88, 1199 (1966). 6. I. A. Bernstein, W. Bennett and M. Fields, J. Am. chem. Soc. 74, 5763 (1952). 7. V. K. E. Weimer and H. G. Eckert, Chem. Ztg. 103, 69 (1979). 8. Private communication from P. Hemesley (Radiochemical Centre, Amersham, England) to D. R. Burfield, Oct. 1978. 9. H. Heusinger, K. Reinhartz, H. Rau and W. Freitag, Kerntechnik 5, 213 (1963). 10. J. Y. Yang and R. B. Ingalls, J. Am. chem. Soc. gS, 3920 (1963). 11. D. R. Burfield, G. H. Gan and R. H. Smithers, J. appl. Chem. Biotechnol. 28, 23 (1978). 12. I. D. McKenzie, P. J. T. Tait and D. R. Burfield, Polymer 13, 307 (1972). 13. D. R. Burfield and C. M. Savariar, Eur. Polym. J. 20, 249 (1984). 14. D. R. Burfield and C. M. Savariar, Macromolecules 12, 243 (1979). 15. C. Mantescu and A. T. Balaban, Can. J. Chem. 41, 2120 (1963). 16. M. A. Long, J. L. Garnett, R. F. W. Vining and T. Mole, 3. Am. chem. Soc. 94, 8632 (1972). 17. D. R. Burfield, K. H. Lee, and R. H. Smithers, J. org. Chem. 4 2 , 3060 (1977). 18. S. L. Madorsky and S. Straus, J. Res. natn. Bur. Stand. 40, 417 (1948).
0014-3057/84 $3.00 + 0.00 Copyright ~ 1984 Pergamon Press Ltd
SYNTHESIS OF TRITIUM LABELLED MONOMERS AND POLYMERS* D. R. BURFIELDand C. M. SAVARIAR Department of Chemistry, University of Malaya, Kuala Lumpur 22-1 l, Malaysia (Received 15 July 1983)
Abstract--The use of P205 for promoting the tritiation of various monomers and polymers has been investigated. Methyl methacrylate and vinyl acetate may be labelled at ambient temperatures by this procedure which is also applicable to labelling polystyrene and poly(~t-methylstyrene).Exchange labelling of polymer substrates is most conveniently carried out in chlorinated hydrocarbons. The rate of tritium exchange increases with solvent polarity and temperature. Monomers of high radiochemical purity may be derived from the thermal depolymerization of tritiated polystyrene, poly(~t-methylstyrene) and poly(methyl methacrylate).
INTRODUCTION Radiolabelled monomers assume importance not only in the synthesis of the corresponding labelled homopolymer but also in the investigation of copolymerization systems. The latter application is highlighted in studies where the copolymers are not amenable to simple spectroscopic or chemical analyses [1,2] or where the co- or ter-monomer is presented only in trace quantities [3]. Labelled polymers in turn have been utilised as standards or calibrants for radiochemical, molecular weight and spectroscopic assay, as well as in a variety of miscellaneous studies. However, the widespread application of such radiotracer methods has been hampered by the limited availability and high cost of labelled monomers. These difficulties are compounded by the chemical instability of certain monomers, notably styrene and its derivatives, which further restricts the shelf-life of and hence ready access to these compounds. The cited constraints provide incentives to develop syntheses of labelled monomers and polymers which can be easily carried out by the individual researcher from readily available low cost starting materials and it is with this problem that this publication is concerned. Tritium represents perhaps the ideal isotope for the above purpose as it is readily and cheaply available at high specific activities (5 Ci/g), is relatively safe (flmax = 0.0186 MeV), has a useful half-life (12.35 y) and may be simply incorporated into a wide variety of organic materials [4]. The suitability of this isotope is further enhanced if consideration is given to aspects such as ease of handling as labelled water and the straightforward assay of the labelled product by liquid scintillation counting. Although tritiation of organic compounds can be effected by a wide variety of methods such as Wilzbach tritium gas exposure, catalytic exchange, or
direct chemical synthesis, many of the methods are not suitable for small scale preparation and require specialised handling techniques or equipment not generally available outside radiochemical centres. The most promising routes to tritium labelled monomers for the average bench chemist are a direct chemical synthesis or an exchange reaction involving labelled water as the source of tritium. Thus styrene labelled in the side-chain has been variously prepared by interaction of tritiated water with styryl magnesium bromide [5]; THF
PhCBr=CH 2 + Mg
, PhCMgBr=CH2 THO
PhCT=CH2
or by catalytic reduction of acetophenone [6] or phenylacetylene [4] with tritium gas: PhCOOCH3 + T2
Pt
, PhCT--CH3
I
OT THO
PHC~---CH + T2
Pa/C
,
, PhCTICH2
PhCT = C H T
Dio×ane
Similarly, tritiated alkyl methacrylates have been derived from the corresponding methacrylic acid through the intermediacy of tritium exchange with labelled water followed by alkylation with diazomethane [7]: CH3
I
CH3
I
CH2=CCO2H + TH°-*CH2=CCO2T CH3
*Presented in part at the 26th IUPAC Conference on Macromolecules, Mainz, 1979. 343
CH2N2 ' CH2~CCO2CH2T
344
D.R. BURF|ELDand C. M. SAVARIAR
or by esterification with the appropriate tritium labelled alcohol [8]:
tation and subsequently purified by repetitive reprecipitation to a constant level of activity.
CH3
CH 3
Polymerization
I
I
Polymers of styrene, vinyl acetate and methyl methacrylate were prepared in benzene solution using benzoyl peroxide as initiator at 60°. Poly(~-methylstyrene) was prepared by sulphuric acid catalysed polymerization in dichloromethane at -78°; poly(4-methyl-l-pentene) was synthesised at 30° with Ziegler-Natta catalyst (VC13/AliBu3) in benzene [12].
CH2 ~---CCO2H + CH2TOH--~ CH2 =CCO2CH2T Again, tritiated vinyl acetate has been synthesised by the catalytic addition of acetic acid, which can also be tritiated on the carboxyl group, to tritium labelled acetylene as illustrated below [9]:
Depolymerization
CaC2 + T H O - - ~ C T ~ C H CH3CO2T
, C T 2= C H C O 2 C H
3
Recently labelled methylvinylketone has been efficiently and simply prepared by base catalysed exchange of the monomer with tritiated water [2]: CH2=CHCOCH3 + THO
K2co3 CH2=CHCOCH2T
Tritiated polymers such as those of methyl methacrylate, n-butyl methacrylate, styrene and vinyl acetate have almost invariably been obtained by polymerization of the respective m o n o m e r although preparation of tritiated polystyrene through Wilzbach labelling has been reported [10]. This paper describes the preparation of a variety of important tritiated monomers and polymers by application of a catalysed tritium exchange reaction between tritiated water and the preformed substrate in the presence of an appropriate catalyst. In addition certain reactive monomers have been prepared by the thermal degradation of the labelled parent polymer. All the techniques employed are restricted to those commonly encountered in the chemical laboratory.
Polymers were thermally degraded by rapid heating to about 400° under vacuum (ca. 10-~-10 -2 mmHg), the volatile products being distilled directly into a receiver cooled with dry-ice. Although a variety of degradation set ups were tried, the best monomer yields (>70%) resulted from the simplest system where the polymer (5-10 g) was heated in a 100 ml round bottom flask over a hot bunsen flame. The volatiles were taken off through a very short distillation head directly into the cooled trap.
Radiochemical purity The radiochemical purity of a labelled monomer was determined by the derivative method where the monomer was polymerized and assayed together with the purified polymer. The radiochemical purity is then given by the expression: ~o Radiochemical purity = Specific activity of polymer (dpm/g) x 100 Specific activity of monomer (dpm/g)
Tritium assay Monomers and polymers were assayed as solutions or gels in a toluene based cocktail containing PPO (4 g/l) and POPOP (0.4 g/I). Counting efficiencies were determined by channels ratio and internal standardization. Details of the assay are discussed more fully elsewhere [13]. RESULTS AND DISCUSSION
Monomer labelling by direct catalytic exchange EXPERIMENTAL
Materials Monomers and solvents of reagent grade quality were purified by standard procedures and dried over activated 3A molecular sieves [11]. Polymers and catalysts were commercial samples of at least 99% purity and were used without further purification. Tritiated water (5 Ci/ml) was obtained from the Radiochemical Centre, Amersham and was diluted with inactive distilled water to an activity of 54 mCi/ml.
Monomer labelling Labelling was carried out by stirring together monomer, solvent, catalyst and tritiated water at ambient temperatures (26-30°). Proportions, catalyst and reaction times are indicated in the text. After exchange, the labelled monomers were decanted off the catalyst residues, washed with several portions of water, dried, distilled and stored over 3A molecular sieves. Certain monomers of low radiochemical purity were further purified by fractionation using a 1 m column packed with glass helices.
Polymer exchange Tritiation was carried out by stirring together catalyst, labelled water and a 10% w/v solution of polymer in dichloromethane under the conditions specified in the text. After exchange, the polymers were isolated by methanol precipi-
Acidic catalysts are known to be effective in the labelling of aromatic and occasionally aliphatic compounds. In particular the efficiency of representative catalysts such as sulphuric acid, phosphoric acid, phosphoric acid-boron trifluoride complex, and aluminium chloride are well documented [4]. Recently we have found that phosphorous pentoxide (P205) alone is a useful exchange catalyst for certain classes of organic compounds. The results of tritium exchange of several monomers with P205 are summarized in Table 1. At ambient temperatures, P205 was found to be a useful catalyst for tritiation of 4-methyl-l-pentene and vinyl acetate to significant levels of incorporation and methyl methacrylate and n-butyl methacrylate to lesser extents. It is clear that P205 is not appropriate for highly acid sensitive monomers such as isoprene, styrene and ~-methylstyrene which undergo vigorous polymerization on contact with the catalyst, presumably via a cationic mechanism. An attempt to label ~-methylstyrene above its ceiling temperature (61 °) also resulted in the monomer forming polymeric products on cooling. This problem could conceivably have been circumvented by distillation of the ~-methylstyrene from the catalyst before cooling.
Tritium labelled monomers and polymers Table I. Direct labellingof monomersvia catalytic exchange Tritiated Volume water CH2CI2 P20~ Time % (ml) (/1Ci) (ml) (g) (day) Incorporation 100 2200t 100 2.5 7 1.7
Monomer Methyl methacrylate
345
Radiochemical purity (O/o) 99.3
Styrene 20 20 0.4 * .~-Methylstyrene 20 20 0.4 * Vinyl acetate 50 1600+ -1.3 I 5 85 n-Butyl methacrylate 4 2.4~: -0.09 1 0.6 nd 4-methyl-l-pentene 20 81+ -0.5 7 35 2 Isoprene 10 --0.2 * T = 28h *Monomerpolymerizedrapidly on contact with catalyst, tSpecific activity40 mCi/ml. :~Specificactivity 0.22mCi,'ml.
Although the successfully labelled monomers were all shown to be substantially chemically pure (b.p., GLC, NMR), the radiochemical purities as determined by polymer derivative analysis were extremely variable. Thus, whereas the radiochemical purity of the tritiated methyl methacrylate is excellent, the purities of vinyl acetate and in particularly 4-methyl-l-pentene were low even after careful fractionation. In the latter case, it seems likely that the exchange reaction was accompanied by isomerization of the olefin to give internal olefins of closely similar physical properties but with little or no polymerization activity, e.g.
=k__
*r"
o
\ ~-H ~
T--L_
-5The tritium distribution in vinyl acetate was investigated by hydrolysis of the poly(vinyl acetate) with methanolic potassium hydroxide, and assay of the resultant polymer.
-[-CH2--CH~
KOH/CH3OH• _[_CH2__CH_]7~
I
I
OCCH 3
OH
PI
0
The poly(vinyl alcohol) retained 53% of the tritium showing that the label was fairly uniformly distributed between the main chain and pendant groups. It is apparent that P205 has potential as an exchange catalyst for alkyl methacrylate and vinyl acetate monomers. Almost certainly tritium incorporation could be increased by the use of elevated temperatures vide injka, althouth this may be accompanied by reduced radiochemical purities.
Polymer labelling by direct catalytic exchange Apart from some recently reported results [14] wherein poly(olefins) and polystyrene were labelled
through the intermediacy of chloroaluminium compounds and a much earlier synthesis of tritiated polystyrene by the Wilzbach technique [10], there appears to be no previous attempts to prepare tritium labelled polymers directly. In this study exchange labelling of polystyrene, poly(a-methylstyrene) and poly(methyl methacrylate) using P205 as catalyst was investigated. Polystyrene labelling was studied most extensively and used as a basis to probe the effects of solvent type, temperature, reaction time and catalyst on tritiation efficiency.
Effect of solvent type on tritium exchange Solvents appropriate for polymer exchange reactions are limited to those which not only dissolve the polymeric substrate but also neither poison the exchange catalyst nor readily undergo proton exchange. The only common solvents which adequately meet these requirements proved to be chlorinated hydrocarbons. Solvents such as THF or dioxane, whilst readily solubilising the polymer, completely inhibited the exchange reaction presumably by complexing the acidic intermediates. Examination of a series of chlorinated solvents under standardised conditions revealed that the rate of exchange was dependent on the solvent polarity (Table 2). The exchange rate was found to increase in step with the dielectric constant of the solvent, the exchange being most rapid for dichloromethane (e = 8.9). This observation is fully consistent with the likely polar nature of the reaction intermediates.
Dependence of exchange activity on catalyst type The efficacy of a variety of mineral and Lewis acids in catalysing labelling of polystyrene was investigated. Sulphuric and phosphoric acids proved to be very much inferior to P205 which however was significantly surpassed by A1C13 (Table 3). The activity of AIC13 is consistent with the known activity of chloroaluminium compounds in promoting rapid exchange with aromatic protons [15, 16]. The marked difference in catalytic activity between P205 and phosphoric acid is informative, since it suggests that P205 is not simply a precursor of the phosphoric acid which then subsequently enacts the exchange. Elsewhere [17], in studies of desiccant efficiency in solvent drying, it was shown that labelled water was very rapidly removed from the bulk of the solvent by treatment with 5~ w/v P205. Furthermore, the absence of residual tritium in the solvent phase precluded the possible emergence of phosphoric acid from the desiccant surface into the solvent bulk.
346
D . R . BURFIELD and C. M. SAVARIAR
CI
\ /
Table 2. Tritium exchange labelling of polystyrene in various solvents Specific activity Dielectric of polystyrene Solvent constant (dpm/g) H C~C
/ \
2.1
8.0 × 10 4
H C1 CCI4 2.2 7.3 x 104 CHCI~CCI 2 3.4 12.9 x 104 CHCI3 4.8 21.0 x 104 CH2CI2 8.9 29.4 x 104 Dioxane 2.2 nil Tetrahydrofuran 7.6 nil N,N-dimethylformamide 36.7 nil Reaction conditions 1 g polystyrene; 20 ml solvent; 0.3 g P205; 1.1/~Ci THO (sp. act. 0.22 mCi/ml); T = 28'; reaction time = 24 hr.
Table 3. Dependence of exchange efficiency on catalyst type Tritiated Specific Polystyrene water % activity Catalyst (g) Solvent (/zCi) Incorporation (dpm/g) 88% H3PO4 0,5 CH2CI2 396t <0.001 8.2 x 103 (0.1 g) (10 ml) H2SO4 0.4 CH2CI2 0.55:~ nd nd (0.2 g) (10 ml) AIC13 0.5 CCI4 0.552 19 4.7 x 103 (0.1 g) (10 ml) P205 2,0 CCI4 2.25 2.9 7.3 × 104 (0.6 g) (50 ml) P205 2.0 CC14 2.2+ 12" (0.6 g) (50 ml) Conditions: temperature = 28°; reaction time = 24 hr. *Incorporation after 3 hr at 80°C. ]'Specific activity 40 mCi/ml. $Specific activity 0.22 mCi/ml.
Consequently it m u s t be concluded t h a t the exchange activity o f the P205 catalyst is limited to its surface on which the tritiated water is adsorbed.
Time dependence of exchange reaction The progressive i n c o r p o r a t i o n o f tritium into a polystyrene substrate was m o n i t o r e d over a period of days at r o o m t e m p e r a t u r e whilst employing P205 as catalyst. T h e results (Fig. 1) show t h a t the extent o f exchange is time dependent, the rate of exchange being approximately c o n s t a n t over the investigated period. This progressive exchange contrasts sharply with the k n o w n rapid but short-lived tritium exchange p r o m o t e d by o r g a n o a l u m i n i u m dichlorides [16], underlining a significant difference in mechanism.
acrylate) however showed no significant exchange even after refluxing for several hours. The facile labelling o f the two a r o m a t i c polymers is consistent with the k n o w n lability of the ring p r o t o n s to acid catalysts. The inertness o f poly(methyl methacrylate) reflects the absence of any readily exchangeable protons a n d possible interference by heteroatoms. In general, P205 is a useful catalyst since, unlike H204 or AICI 3 it does not lead to direct chemical interaction with and hence possible modification of the polymer substrate.
12 lO
Temperature dependence of exchange reaction R a p i d exchange reactions are useful from a preparative viewpoint as they reduce the time required for the synthesis. Elevated temperatures n o r m a l l y enhance the exchange activity a n d such is seen to be the case with polystyrene labelling (Table 3). Carrying out the exchange reaction in c a r b o n tetrachloride u n d e r reflux ( ~ 80 °) is seen to increase the tritiation rate by a factor of a b o u t 33 c o m p a r e d to exchange at a m b i e n t temperatures.
Labelling of polymer substrates P205 was f o u n d to be effective as a catalyst for tritiation o f polystyrene and poly(ct-methylstyrene) u n d e r mild conditions (Table 4). Poly(methyl meth-
g
8
~6 ,,o
/
2
{}{•
I
2
I
I
I
4 6 8 Time/days
I
10
Fig. 1. Tritiation of polystyrene as a function of time. Reaction conditions: 2.5 g polymer in 50ml CCI4; 0.8 g P205; 10 pl THO (2.2 #Ci); temperature = 28%
Tritium labelled monomers and polymers
347
Table 4. Direct labelling of polymers and indirect monomer synthesis via polymer degradation
Polymer Polystyrene
Mass (g) 2
Tritiated water (# Ci) 2.2*
5
1100t
12.8
595t
Polystyrene Poly(~-methylstyrene)
Solvent CCI4 (50 ml) CH2CI2 (50 ml) CH2CI2 (100 ml)
Catalyst P20~ (0.6 g) AICI3 (1.0 g) P205 (2.1 g)
Time (day) l 1 1
Radiochemical purity of ~o derived monomer§ Incorporation (~,,i) 2.9 --50 3.9
95 100.1
Poly(methyl 0.5 0.55* CH2CI2 P205 7 nd methacrylate) (10 ml) (0.15 g) -101.4 Poly(methyl Methacrylate)~ Exchange temperature = 28°: *Specificactivity0.22 mCi/ml, tSpecificactivity40 mCi/ml. ,+Labelledpolymerderived from tritiated monomer. §Monomers derived in at least 70~oyield by thermal depolymerization at 400".
Labelled monomer synthesis through polymer polymerization
de-
Certain polymers, notably those derived from ~,ct-disubstituted olefins such as ~-methylstyrene, undergo facile depolymerization at elevated temperatures with almost quantitative yield of monomer.
H2C L
~ n CH2=C /
REFERENCES
\
Ph
.
exchange reactions in both monomeric and polymeric substrates. Tritium labelled monomers such as methyl methacrylate and vinyl acetate and tritiated polymers of styrene and ~t-methylstyrene may be readily synthesised by such procedures. Labelled monomers may also be obtained by thermal depolymerization of tritiated polymers of styrene, ct-methylstyrene and methyl methacrylate.
Ph
Pyrolysis of tritium labelled polymers should thus lead to the corresponding labelled monomer. This was indeed found to be the case and good yields of labelled styrene and a-methylstyrene were obtained from their parent polymers on depolymerization at temperatures around 400 ° (Table 4). Thus although direct catalytic exchange is prohibited under the conditions employed, the labelled monomers can be readily obtained by degradation of the tritiated polymer. The resulting ~t-methylstyrene is effectively radiochemically pure but the tritiated styrene had a somewhat lower purity of 94~. This difference reflects the relative cleanness of the depolymerization since polystyrene degradation is known to be accompanied by byproducts such as toluene and styrene dimers [18]. Polymer depolymerization is also appropriate to alkyl methacrylate polymers. Thus, for example, m o n o m e r yield and radiochemical purity of methyl methacrylate are found to be high (Table 4). This is of some interest as although poly(methymethacrylate) is not readily labelled by the investigated procedures, alkyl methacrylate polymers with 3H- or '4C-labels are readily and cheaply available commercially whereas their respective monomers are not. CONCLUSION Reagent grade P205 may be used to catalyse tritium
1. G. Ayrey, Adv. Polym. Sci. 6, 142 (1969). 2. D. R. Burfield and C. M. Savariar, Eur. Polym J. 16, 1003 (1980). 3. D. R. Burfield and C. M. Savariar, J. Polym. Sci., Polym. Lett. Ed. 20, 515 (1982). 4. E. A. Evans, Tritium and its Compounds 2nd edn. Butterworths, London (1974). 5. W. A. Pryor, R. W. Henderson, R. A. Patsiga and N. Caroll, J. Am. chem. Soc. 88, 1199 (1966). 6. I. A. Bernstein, W. Bennett and M. Fields, J. Am. chem. Soc. 74, 5763 (1952). 7. V. K. E. Weimer and H. G. Eckert, Chem. Ztg. 103, 69 (1979). 8. Private communication from P. Hemesley (Radiochemical Centre, Amersham, England) to D. R. Burfield, Oct. 1978. 9. H. Heusinger, K. Reinhartz, H. Rau and W. Freitag, Kerntechnik 5, 213 (1963). 10. J. Y. Yang and R. B. Ingalls, J. Am. chem. Soc. gS, 3920 (1963). 11. D. R. Burfield, G. H. Gan and R. H. Smithers, J. appl. Chem. Biotechnol. 28, 23 (1978). 12. I. D. McKenzie, P. J. T. Tait and D. R. Burfield, Polymer 13, 307 (1972). 13. D. R. Burfield and C. M. Savariar, Eur. Polym. J. 20, 249 (1984). 14. D. R. Burfield and C. M. Savariar, Macromolecules 12, 243 (1979). 15. C. Mantescu and A. T. Balaban, Can. J. Chem. 41, 2120 (1963). 16. M. A. Long, J. L. Garnett, R. F. W. Vining and T. Mole, 3. Am. chem. Soc. 94, 8632 (1972). 17. D. R. Burfield, K. H. Lee, and R. H. Smithers, J. org. Chem. 4 2 , 3060 (1977). 18. S. L. Madorsky and S. Straus, J. Res. natn. Bur. Stand. 40, 417 (1948).