Dioxepane synthesis

Agarwal, S. (2007) Radical ring opening and vinyl copolymerization of 2,3,4,5,6 pentafluorostyrene with 5,6-benzo-2-methylene-13-dioxepane synthesis and structural characterization using ID and 2D NMR techniques. / Polym. Res., 13 (5), 403. 

FIGURE 6 Synthesis of PCL by the free radical polymerization of 2-methylene-l,3-dioxepane. (From Ref. 51.)... 

Bailey, W, J., Ni, Z., and Wu, S.-R., Synthesis of poly-e-capralactone via a free radical mechanism. Free radical ringopening polymerization of 2-methylene-l, 3-dioxepane, J. Polym. Sci., Polym. Chem. Ed.. 3021-3030, 1982. 

By utilizing a combination of RAFT and cationic ROP, the synthesis of [poly(methyl methacrylate)][poly(l,3-dioxepane)][polystyrene] miktoarm star terpolymers was achieved [182], The approach involved the synthesis of PS functionalized with a dithiobenzoate group by RAFT polymerization and subsequent reaction with hydroxyethylene cinnamate (Scheme 98). The newly created hydroxyl group was then used for the cationic ring opening polymerization of 1,3-dioxepane (DOP). The remaining dithiobenzoate group was used for the RAFT polymerization of methyl methacrylate. 

A third example combines cationic ROP and ATRP for the synthesis of (polytetrahydrofurane)(poly-l,3-dioxepane)(PS) miktoarm stars (Scheme 99). The initiating sites for the above polymerization were created step-by-step from amino-succinic acid (Scheme 99). 

A high level of activity continues in connection with the synthesis of antimalarial artemisinin analogues and congeners, in which the 1,2-dioxepane moiety is embedded. Recent examples include the syntheses of various 10-substituted deoxoartemisinins of type 123 (eg. R1 = Cl COMe) from dihydroartemisinin acetate, and of type 124 (eg. R2 = a-OH, R3 = Me), from Grignard reagent addition to 10-(2-oxoethyl)deoxoartemisinin . 

This indicates the possibility of making addition polymers biodegradable by the introduction of ester linkages in to the backbone. Since the free radical ring-opening polymerization of cyclic ketene acetals, such as 2-methylene-1,3-dioxepane (1, Scheme I), made possible the introduction of ester groups into the backbone of addition polymers, this appeared to be an attractive method for the synthesis of biodegradable addition polymers. 

Mathisen T, Albertsson A-C (1989) Polymerization of l,5-dioxepan-2-one. 1. Synthesis and characterization of the monomer l,5-dioxepan-2-one and its cyclic dimer 1,5,8, 12-tetraoxacyclotetradecane-2,9-dione. Macromolecules 22 3838-3842... 

Lofgren A, Albertsson A-C, Dubois P, Jerome R, Teyssie P (1994) Synthesis and characterization of biodegradable homopolymers and block copolymers based on l,5-dioxepan-2-one. Macromolecules 27 5556-5562... 

Palmgren R, Karlsson S, Albertsson A-C (1997) Synthesis of degradable crosslinked polymers based on l,5-dioxepan-2-one and crosslinker of bis- -caprolactone type. J Polym Sci A Polym Chem 35 1635-1649... 

M. E. Butcher, J. C. Ireson, J. B. Lee, and M. J. Tyler, Seven and eight membered ring sugars and related systems The synthesis of some septanose rings from dioxepans, Tetrahedron, 33 (1977) 1501-1507. 

Synthesis of 1,2-dioxepane derivatives can be achieved through mainly four methods, three of which have the potential 0-0 bond already in one reactant, namely ozone, oxygen gas, or a hydroperoxide moiety. The fourth method involves the linking of two oxygen atoms to form a 1,2-dioxepine bond. 

For the application of this method in the enantioselective total synthesis of heliannuols D and A, see <2000J(P1)1807>. An isomeric mixture of dioxepane 108 was cleaved with iV-bromosuccinimide to give bromoester 109 (Scheme 26) <2003BMC2739>. For the preparation of 108, see Section 13.11.9.2. Ring opening of 109 occurred regioselectively on the least hindered carbon. 

Reductive cleavage of dioxepanes with borane-THF complex (THF = tetrahydrofuran) leads to 1,4-diols. This procedure has found application in the synthesis of discrete polyethers (Scheme 27) <2003JOC9166>. 

In the course of a total synthesis of resiniferatoxin, an unexpected ring extension occurred, when 1,3-dioxane 236a was treated with an acid in chloroform. The ring extension was confirmed by acid-catalyzed rearrangement of diol 236b into dioxepane 237 (Scheme 70) <20040L4371>. 

Mulzer et al. have extended the applicability of the insertion reaction of ketene into an acetal, to that of a substituted ketene into a 1,3-dioxalane to provide an elegant synthesis of 6,6-dichloro-l,4-dioxepan-5-ones (Equation 13) <1996AGE1970>. 

The monomers that have been used for the synthesis include glycolide, lactide, (3-propiolactone, (3-butyro lactone, y-butyrolactone, 6-valerolactone, e-caprol-actone, l,5-dioxepan-2-one, pivalolactone, l,4-dioxane-2-one, 2-methylene-1, 3-dioxolane, 2-methylene-l, 3-dioxepane, etc. The structures of some of these monomers are given in Table 1. 

The synthesis of l,5-dioxepan-2-one (DXO) was earlier reported from acrylonitrile and ethylene glycol [54]. Another approach was via ring closure of methyl 3-(2-hydroxyethoxy)propionate by an organometallic transesterification cata-... 

The cyclic tin alkoxides have the additional advantage of offering a convenient synthetic pathway for the synthesis of macromers, triblock, and multiblock copolymers [81,82]. Macromers from l-LA [83],e-CL [84], and l,5-dioxepan-2-one (DXO) [85] have been synthesized as well as triblock poly(L-LA-b-DXO-b-L-LA) [86] and multiblock copoly(ether-ester) from poly(THF) and e-CL [87]. The polymerization proceeds by ring expansion and the cyclic structure is preserved until the polymerization is quenched by precipitation. 

Scheme 7. Synthesis of l,4-dioxepan-2-one from 1,3-propanediol and chloroacetic acid sodium salt...

The most characteristic feature of the cationic polymerization of cyclic acetals, however, is an excessive participation of the polymer chain in the polymerization processes. This is exemplified by the results of attempted synthesis of block copolymer containing segments of poly(l,3-dioxolane, DXL) and poly(l,3-dioxepane, DXP) [130]. 

For instance, in the last decade synthesis of poly(ester-alt-ether) was intensively studied. A common enzyme used in these syntheses is CALB. Polymerization of l,5-dioxepan-2-one (DXO) was performed by enzyme-catalyzed ROP in order to avoid contamination of product polymers by toxic organometallic catalysts [92], High molecular weight of poly(DXO) was obtained (Mn = 56000 Mw = 112000, 97% yield) at 60 °C for 4h. The polymerization had the characteristics of a living polymerization, as indicated by the linearity of plots between M and monomer conversion, meaning that the product molecular weight could be controlled by the stoichiometry of the reactants. Similarly, Nishida et al. [91] carried out enzymatic ROP of l,4-dioxan-2-one at 60 °C catalyzed by Novozym 435 that resulted in a polymer with Mw = 41000 in 77% yield. 

Block Copolymers. Several methods have already been used for the synthesis of block copolymers. The most conventional method, that is, the addition of a second monomer to a living polymer, does not produce the same spectacular results as in anionic polymerization. Chain transfer to polymer limits the utility of this method. A recent example was afforded by Penczek et al. (136). The addition of the 1,3-dioxolane to the living bifunctional poly(l,3-dioxepane) leads to the formation of a block copolymer, but before the second monomer polymerizes completely, the transacetalization process (transfer to polymer) leads to the conversion of the internal homoblock to a more or less (depending on time) statistical copolymer. Thus, competition of homopropagation and transacetalization is not in favor of formation of the block copolymers with pure homoblocks, at least when the second block, being built on the already existing homoblock, is formed more slowly than the parent homoblock that is reshuffled by transacetalization. 

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