Macrocyclic Polymerizations of Lactones - American Chemical Society

Chapter 11

Macrocyclic Polymerizations of Lactones: A New Approach to Molecular Engineering Downloaded by STANFORD UNIV GREEN LIBR on April 10, 2013 | http://pubs.acs.org Publication Date: January 15, 2001 | doi: 10.1021/bk-2000-0764.ch011

Hans R. Kricheldorf, Soo-Ran Lee, Sven Eggerstedt, Dennis Langanke, and Karsten Hauser Institut für Technische und Makromoleculare Chemie, Bendesstrasse 45, D-20146 Hamburg, Germany

Cyclic tin alkoxides like 2,2-dibutyl-2-stanna-1,3-dioxepane were used as initiator for the ring-opening polymerization of various lactones. In this way series of macrocyclic polyesters were obtained without any competitive formation of linear polymers. Under optimized conditions these macrocyclic polymerizations obey the pattern of "living polymerizations". Therefore, the number average molecular weight (Mn) can be controlled by the monomer/initiator ratio, and macrocyclic block copolyesters can be prepared by sequential copolymerization of two lactones. Macrocyclic oligomers and polymers having various types of backbones were prepared by "ring-closing polycondensation" of Bu Sn(OMe) with various oligomeric or polymeric diols, such as poly(ethylene glycol)s. These tin-containing macrocycles were, inturn, used as "macroinitiators" for polymerizations of lactones. Ring-opening by acylation with functional acid chlorides or anhydrides yielded telechelic polylactones. Regardless of size and structure all tin-containing macrocycles can be used as bifunctional monomers for polycondensations, for instance, with dicarboxyl acid dichlorides. These "ring-opening polycondensations" are useful for syntheses of biodegradable multiblock copolymers, particularly for thermoplastic elastomers. 2

2

Polyesters prepared by ring-opening polymerization of lactones and aliphatic cyclocarbonates play a great role among the biodegradable materials, particularly polyesters based on L - or D,L-lactic acid. Such polyesters comprise homo-polyesters, © 2000 American Chemical Society In Polymers from Renewable Resources; Scholz, C., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2001.

135

136 random copolyesters, triblockcopolyesters, multiblock copolyesters and even starshaped polyesters. The ring-opening polymerization of the monomers may proceed by three mechanisms: anionic, cationic and coordination-insertion mechanisms. From the preparative point of view the coordination-insertion mechanisms are particularly important, because they may yield high molecular weights and high yields of all lactones or cyclocarbonates, and because they proceed without racemization of L lactide or L - and Ο-β-butyrolactone. The most widely used initiators are tin compounds, such as SnCl * η H 0 , Sn (2-ethyl hexanoate) , Bu SnO, B^SniOMe^ or Bu SnOMe. Our ongoing research and the present review deal with cyclic tin alkoxides, such as 1 - 7, part of which (1-3) has been described in the literature (2 j), but never used as initiator before. When cyclic tin alkoxides are used as initiators (6 -16) they yield macrocyclic oligoesters and polyesters without any linear byproducts. Hence, these "macrocyclic polymerizations" offer an easy access to macrocycles with a broad variation of structure and molecular weight. Furthermore, the high reactivity of the Sn-0 bond also allows a broad variation of post-reactions with elimination of the R Sn group. 2

2

2

2

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3

2

Macrocyclic Polymerizations Five- and sixmembered cyclic tin alkoxides have the tendency to dimerize (eq. 1) to alleviate the ring strain (2 - 5). The dimers (e.q. l b , 2b, 3b or 4b) may possess high melting points ( > 150°C) (2 - 5), and are poorly soluble in lactones. When a rapid homogenization of initiator and monomer cannot be achieved, the chain growth is faster than the entire initiation process, and average degrees of polymerization (DPs) are higher than the monomer/initiator (M/I) ratios (6 - #). Apparently for thermodynamic reasons the sevenmembered ring of 3a is a mainly monomeric liquid which is stable on storage at £ 20°C and which is miscible with most monomers. Therefore, this heteroeycle, 2,2-dibutyl-2-stanna-l,3-dioxepane. (DSDOP), was used as initiator for most preparative purposes (10 - i i ) (eq.2). When DSDOP-initiated polymerizations of ε-caprolactone (ε-CL) or δ-valerolactone (δ-VL) are conducted at temperatures < 80°C with an optimized reaction time, the DPs parallel the M/I ratios, and number average molecular weights (M^s) up to 120 000 were obtained (loX The polydispersities (1.3 -1.6 depending on the temperature) are higher than those of a classical "living polymerization". Reasons for the broader polydispersities are a rather slow initiation ,on the one hand, and transesterification including "back biting degradation", on the other. These side reactions are difficult to avoid completely, because tin compounds belong to the best transesterification catalysts. The polydispersities not only depend on the reaction conditions, but also on the lactone. Polydispersities as low as 1.25 were found for DSDOP-initiated polymerizations of β-

In Polymers from Renewable Resources; Scholz, C., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2001.

137 D,L-butyrolactone (17) and further studies will probably show that even lower polydistersities can be obtained. A particular advantage of tin alkoxide-initiated polymerizations is the rather high chemical and thermal stability of the Sn-O bonds. They are sensitive to hydrolysis or alcoholysis, but they can be stored in closed flask for months and years. Therefore, the tin containing macrocyclic polyesters can initiate a second lactone, so that macrocyclic block copolyesters (9) can be prepared (eq. 3) X In this case time and temperature need again to be optimized to minimize transesterification. However, when mixtures of two lactones or lactones and trimethylene carbonate are copolymerized by initiation with DSDOP also random copolymers can be obtained ). When the 2-stanna-thiolane (4) is used as initiator at moderate temperature ( < 120°C), the insertion of lactones exclusively occurs at the Sn-0 bond and macrocyclic polyesters of the structure 10 will result (7).


1,18

1,8

The formation of Sn-S bond is not only kinetically favored, it is also thermodynamically more stable than a Sn-0 bond, and thus, its reactivity towards lactones is significantly lower. Furthermore, it should be mentioned that initiation with the unsaturated heterocycles 5 and 6 yields polylactones having a reactive cis-double bond somewhere in the middle of the chain (/p). Initiation with the spirocompound produces polylactones in the form of "nanopretzels" (11).

Cyclization of polymeric diols The rapid equilibration of the initiators l a - 4a/ib - 4b and the NMR spectra of Bu SnOMe (18) demonstrate that the exchange of RO groups between different SnOR compounds may be fast above room temperature, and thus, the reaction products are thermodynamically controlled. This characteristic property of Sn-OR compounds has several interesting consequences. First, when a tin-containing macrocycles are large enough so that no ring strain exists anymore, they are thermodynamically stable. Therefore, the macrocyclic oligo and polyesters 8, 9 and 10 will not oligomerize in such a sense that larger cycles containing two or more Sn atoms are formed. Second, high molecular weight polymers containing Sn-O bonds cannot exist above room temperature. Third, "polycondensations" of Bu SnX compounds with long diols will never yield polymers but the smallest thermodynamically stable macrocycles. These conclusions represent nothing extraordinary from the thermodynamical point of view, because for reasons of entropy almost all polymers will break down into cycles when the energy of activation is sufficiently lowered. 3

2

2

The experimental evidence for these conclusions was obtained from "polycondensations" of Bu Sn(OMe) with various monodisperse and polydisperse poly(ethylene-glycol)s (eq. 4)(15). The marcocyclic structure (11) of the reaction products was proven by viscosity and SEC measurements, by mass spectrometry and 2

2


138

,0-(ÇH ) 2

BifcSn \ Ο—CH

Ο—(CH ) -€H -0 2

2

BifcSn

SnBi&

(D

A—CHz-iCH^g-i

2

lb : η = 1

la : η = 1

2b : η = 2

2a : η = 2 Downloaded by STANFORD UNIV GREEN LIBR on April 10, 2013 | http://pubs.acs.org Publication Date: January 15, 2001 | doi: 10.1021/bk-2000-0764.ch011

H

n

3b : η = 2

3a : η = 3

Ο—CH —CH —S 2

O—CH

2

2

Bu Sn

BifcSn

SnBu2

2

S—CH

i—CH—CH—J)

2

2

2

4b

4a

O—CH

,0—CH —ÇH 2

2

BifcSn "0-CH

Βνφη

\ 0—CH —CH

2

2

O—CH^ C H — /

Bua6n

C

2

SnBu

2

7


(2)

139

,0—CHz—Çth


\

+

O

CO

O—CHx—Cth (3)

(CHjJs—CO-

"O GHJ2 ÇE$i ftifrTTT ΓΤΤί

£o—(ends—co-Jj [CHjfe—CO—j—O—Ofe-Cffe 8 (4)

[4*

;—CH2—CO

-O—(CUDs—CO-

—CH2—CO

-O—(CH2)5—CO-

BteSn

i—Cffe-Cfb

O (

-O—CH2—CH2

10

^


140 U 9

S N M R spectroscopy. Analogous results were obtained by polycondensation of Bu Sn(OMe) with commercial poly(tetrahydrofuran) diols (16). Using commercial poly(propylene glycol)s, poly(styrene) diols, hydrogenated poly(butadiane) diols or poly(siloxane) diols a broad variety of tin-containing macrocycles became accessible by this simple methods. As exemplified by eq. (5) all these macrocyclic oligomers or polymers can be used as "macroinitiators" for the polymerization of lactones. In this way various macrocyclic block copolymers can be prepared which, as described below, can be transformed into an even greater variety of tin-free polymers. A first interesting example of such a transformation is the ring-opening with dimercapto ethane (eq. 6). At room temperature a selective elimination of the Bu Sn group takes place without cleavage of ester groups, and telechelic A-B-A triblock copolymers having free OH endgroups can be isolated (16). 2

2


2

Telechelic Polyesters As illustrated by equation (6) the treatment of tin-contaning macrocycles with dimercaptoethane is a simple method to prepare telechelic oligo - or polyesters having two OH endgroups which can further be modified in various ways, for instance by chain extension with diisocyanates. When the removal of Bu Sn groups with dimercaptoethane can be applied to the macrocycles 9, telechelic block copolyesters of two lactones are obtained. When applied to the "nanopretzels" (11) four armed stars havingfreeOH endgroups are the reaction products (8). The Sn-0 bonds of the tin-containing macrocycles react easily with carboxylic acid chloride (eq. 7). The reaction conditions need to be optimized depending on the reactivity of the acid chloride to obtain 97 - 100 % fimctionalization (as evidenced by 400 MHz *H NMR spectra). Almost any kind of functional acid chloride can be used, so that a broad variety of telechelic polylactones can be synthesized and used for chain extension and other modifications of the endgroups (11). The tin containing macrocycles also react with carboxylic acid anhydrides. Functionalization with methacrylic anhydride (eq. 8) (11) yields telechelic polylactones which by copolymerization with suitable comonomers (e.g. hydroxy-ethyl methacrylate) may be useful as bone cements. Unfortunately acid chloride or anhydrides of N-protected amino acids or peptides are unstable and difficult to prepare. However, telechelic polylactones having amino acid or peptide endgroups can be synthesized by the reaction of tin-containing macrocycles with N-protected aminoacid thioarylesters (eq. 9) (19), which are easy to prepare from thiophenols and dicyclohexyl carbodiimide. This new coupling reaction is free of racemization and can also be used to bind pénicilline derivatives to polylactones. Finally, it should be mentioned that the Boc protecting group was removed by anhydrous trifluoroacetic acid in CH C1 without cleavage of the polyester chain (19). The liberated amino endgroups (stabilized as 2

2


2

141 trifluoroacetates) can, in turn, serve as initiators for the polymerization of α-amino acid N-carboxyanhydrides or for stepwise peptide syntheses.


Ring-opening Polycondensations: Ring-opening polymerization is usually the only synthetic strategy which allows to transform cyclic monomers into polymers (with Ziegler-Natta type polymerizations of a few cycloolefins being the only exception). We have recently demonstrated that the Sn-0 bonds of tin-containing macrocycles, such as 3a or 8 are reactive enough to use them as bifanctional monomers for polycondensations (12, 13, 16). This new synthetic approach illustrated in eqs. (10) and (11) is called ringopening polycondensation . In addition to dicarboxylic acid dichlorides the bisthioaryl esters of dicarboxylic acids may be used as electrophilic reation partners of the tincontaining macrocycles (20). The number of small tin-containing heterocycles which can serve as monomers for the ring-opening polycondensation is relatively small, but they can be used as initiators for ring-opening polymerizations (eq. 2), and the resulting tin-containing macrocyclic polymers (e.g. 8) can be used for in situ polycondensations (eq. 11). In other words, ring-opening polymerizations and ringopening polycondensations can be combined in an "one-pot procedure" and this combination is called ROPPOC method. When macrocyclic block copolymers such as 9 or 12 are used as monomers for the polycondensation, multiblock copolymers are the reaction products. Therefore, the ROPPOC method is particularly useful for the synthesis of a broad variety of multiblock copolyesters with tailored properties. An interesting group of these multiblock copolymers are biodegradable thermoplastic elastomers composed of a flexible soft segment (e.g. poly(ethylene glycol)s or poly (THF)diols) and crystalline polyester segments (16).

Conclusion Difunctional tin alkoxides (R Sn(OR')2) offer several new synthetic strategies in the field of degradable materials: first, the macrocyclization of preformed polymeric diols, second, the macrocyclic polymerization of lactones, third, the synthesis of telechelic oligo- and polylactones in an "one pot procedure" and fourth, the ringopening polycondensation possibly in direct combination with the macrocyclic polymerization of lactones. 2


Bu2Sn(OMe)2 + H - ^ O — C H —CHr-j—OH —CH -^ χ 2

2

-2 MeOH

,Ο—CH—CH—I Downloaded by STANFORD UNIV GREEN LIBR on April 10, 2013 | http://pubs.acs.org Publication Date: January 15, 2001 | doi: 10.1021/bk-2000-0764.ch011

2

2

ç

BifcSn O—CH —CH —Ο 2

+

2

Ο

(A)

ν

CO

11

Ο—(A)

CO-

Ό—CH -CH 2

2

1

l -

4— x-1

Bi^Sn O—(A)—CO-

-O—CH —CH —Ο 2

2

m 12

+

(HS—CH ) 2

S—CH / Bu&Sn

2

S—CH

HO—(A)—CO-I—Ο—CH —CH 2

2

2

2

0—CO—(A)—OH

13


143

R—CiO—0—(CH )5—CO -O—(CH )4—O—OC—(CH )s—O—CO—R 2

2

2


+ 2R-COC1

O—(CIÎ2)5—C04O—CH c*Jo—c -CH H Bu&Sn 2

(7)

2

2

4

(Œ )5—C040-CH2-CH 2

BieSiiCl

2

+ 2 (CH2=CMeCO) 0

Bu2Sn(02C—CMe=CH )

2

2 2

(8)

Me

Me

CH2K:~C0^0—(CH )——(CH ) -0-£cO—(Œ )5-0^-CO—i=CH: 2

2

Me

4

2

^ - ^

8 + 2 BocNH—CH—CO—S - (Cy)

' Cl

(9)

- Bi^Sn(S-C6H4Cl)

2

Me Boc—NH—d:H—CQÔ—(CH )s—C0J0—CH -CH 2

2

Boc—NH—ÇH—CO-J-O—(Œ )5ÔJ-0—CH —CH 2

Me

^

2

2

2

-·


144

O—CH —ÇH 2

BiçSn \

+ O—CH —CH 2


2

C1CO—(CH^jj-COCl

2

BiçSnCb

(10)

-O—(CH ) —O—CO—(CH ) 2

4

2

[θ—(CH )5—Coj-0—CH —ÇH 2

2

CO—S—QH5

2

+

BiçSn

jji—(CH )5—Cojo—CH —ιCH 2

2

(A) CO—S—ιQ H S

2

Bu Sn(S-C H5) 2

6

-CO—(A)—CO-Ô—(CH )5—CO^-0—(CH^—O^-CO 2

(H)

2

(CH)s—oJ|—\


2

145


Literature Cited ( 1) Bornstein, J., Laliberté, B.R., Andrews, T.M., Montermoso, J.C., J. Org. Chem. 1959, 24, 886 ( 2) Mehrotra, R.C.; Gupta, V.D., J. Organomet. Chem. 1965, 4, 145 ( 3) Considine, W.J., J. Organomet. Chem. 1966, 5, 263 ( 4) Pommier, J.C., Valade, J., J. Organomet. Chem. 1968, 12, 433 ( 5) Smith, P.J., White, R.F.M., J. Organomet. Chem. 1972, 40, 341 ( 6) Kricheldorf, H.R., Lee S.-R., Macromolecules 1995, 28, 6715 ( 7) Kricheldorf, H.R., Lee, S.-R., Bush, S., Macromolecules 1996,29, 1375 ( 8) Kricheldorf, H.R., Lee, S.-R, Macromolecules 1996, 29, 8689 ( 9) Kricheldorf, H.R., Lee, S.-R., Schittenhelm, N . , Macromol.Chem. Phys. 1998, 199, 273 (10) Kricheldorf, H.R., Eggerstedt, S., Macromol. Chem. Phys. 1998, 199, 283 (11) Kricheldorf, H.R., Hauser, K., Macromolecules 1998, 31, 614 (12) Kricheldorf, H.R., Eggerstedt, S., J. Polym. Sci. Part A Polym. Chem. 1998, 36, 1373 (13) Kricheldorf, H.R., Eggerstedt, S., Macromolecules 1998, 31, in press (14) Kricheldorf, H.R., Eggerstedt, S., Krüger, R., Macromol. Chem. Phys. 1999 (Macrocycles 6.) (15) Kricheldorf, H.R, Langanke, D., Macromol.Chem.Phys. in press (Macrocycles 7.) (16) Kricheldorf, H.R., Langanke, D., Macromol. Chem. Phys. 1999 in press (Macrocycles 8.) (17) Kricheldorf, H.R., Lorenc, Α., Damrau, D.-O., manuscript in preparation (18) Davies, A.G. in "Organotin Chemistry" VCH, Weinheimn New York, p. 169 (19) Kricheldorf, H.R., Hauser, K., Macromol.Rapid Commun.1999 in press ("Polylactones 46.") (20) Kricheldorf, H.R., Hauser, K., Krüger R., manuscript in preparation


Macrocyclic Polymerizations of Lactones - American Chemical Society

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