Lactones from cyclic anhydrides

In this category a collection of some unsorted methods for the synthesis of 8-lactones are described. Canonne et al. have reported a one-step spiroannelation for the synthesis of spiro-8-lactones from cyclic anhydrides [117]. Addition of 1,4-bis(bromo-magnesio)butane to spirocyclic anhydride 312 led to intermediate 314 via the formation of 313, and subsequent treatment with HCl provided spiro-8-lactone 315 (Scheme 69). The scope of this method was further demonstrated with several anhydrides to synthesize a variety of spiro-8-lactones. 

The photolysis of carboxylic acids and derivatives as lactones, esters and anhydrides can yield decarboxylated products 253>. This reaction has been utilized in the synthesis of a-lactones from cyclic diacyl peroxides 254) (2.34) and in the synthesis of [2,2]paracyclophane by bis-decarboxylation of a lactone precursor (2.35) 255). This latter product was also obtained by photoinduced desulfurization of the analogous cyclic sulfide in the presence of triethyl phosphite 256). 

Besides the more often-used acyl donors mentioned above, others which would also ensure an irreversible type of reaction have been investigated [170]. Bearing in mind that most of the problems of irreversible enzymatic acyl transfer arise from the formation of unavoidable byproducts, emphasis has been put on finding acyl donors that possess cyclic structures, which would not liberate any byproducts at all. However, with candidates such as lactones, lactams, cyclic anhydrides (e.g., succinic acid anhydride [171]), enol lactones (e.g., diketene [172, 173]), and oxazolin-5-one derivatives [174], the drawbacks often outweighed their merits. 

The principles set forth above account reasonably well for the course of bifunctional condensations under ordinary conditions and for the relative difficulty of ring formation with units of less than five or more than seven members. They do not explain the formation of cyclic monomers from five-atom units to the total exclusion of linear polymers. Thus 7-hydroxy acids condense exclusively to lactones such as I, 7-amino acids give the lactams II, succinic acid yields the cyclic anhydride III, and ethylene carbonate and ethylene formal occur only in the cyclic forms IV and V. 

Cyclic tetrafluoro ethers are also the main or sole products of the sulfur tctrafluoridc fluorination of phthalic and pyromellitic acids, or their anhydrides, possessing two bulky ortho substituents (e.g., CF3. N02, Br. Cl or even Me). These substituents create steric crowding which pushes two neighboring carboxylic acid groups towards each other and forces cyclization acid anhydrides and difluoro lactones are the intermediates and they may be isolated from reactions carried out under sufficiently mild conditions. Thus, reaction of 3,6-bis(trifluoromcthyl)bcn-zcnc-1,2-dicarboxylic acid (4) with sulfur tctrafluoridc at ambient temperature results in dehydration to give exclusively the corresponding cyclic anhydride 5 at 60"C a mixture of the anhydride 5, 3,6-bis(trifluoromethyl)phthaloyI difluoride (6) and 3,3-difluoro-4,7-bis(trifluoro-methyl)isobenzofuran-l(3//)-one (7) is obtained, but at 200"C the final product, 1,1,3,3-tct-rafluoro-4,7-bis(trifluoromethyl)-l,3-dihydroisobenzofuran (8), is formed as the sole product.137... 

Since oxiranes are representative heterocyclic monomers containing an endo-cyclic heteroatom, and the most commonly polymerised of such monomers, they have been subjected to copolymerisations with heterocyclic monomers containing both an endocyclic and an exocyclic heteroatom. Coordination copolymerisations of heterocyclic monomers with different functions are focused on oxirane copolymerisation with cyclic dicarboxylic acid anhydride and cyclic carbonate. However, the statistical copolymerisation of heterocyclic monomers with an endocyclic heteroatom and monomers with both endocyclic and exocyclic heteroatoms have only a limited importance. Also, the block copolymerisation of oxirane with lactone or cyclic dicarboxylic acid anhydride is of interest both from the synthetic and from the mechanistic point of view. Block copolymerisation deserves special interest in terms of the exceptionally wide potential utility of block copolymers obtained from comonomers with various functions. It should be noted, however, that the variety of comonomers that might be subjected to a random, alternating and block polymerisation involving a nucleophilic attack on the coordinating monomer is rather small. 

The ability to accept electrons from donors is particularly pronounced in acrylic acid derivatives [85] its alkyl esters [78, 87, 88], acrylonitrile [88], acrylamide, hydroxylacrylates [85], and further in styrenes substituted with an electronegative atom or group m-nitrostyrene, 2,6-dichlorostyrene [86], / -nitrostyrene [89] bicyclobutane-1-carbonitrile [89] lactones /J-propio-Iactone [85], sulfolactone vinyl ketones [87] unsaturated dicarboxylic acids and their derivatives diethyl fumarate, fumaronitrile [90], ROOC—N— N—COOR [86], cyclic anhydrides of diacids [91 ], particularly maleic anhydride [78, 92] ethylenes substituted with electronegative groups [93, 95]... 

A large number of copolymers of cyclic ethers, cyclic sulphides and cyclic formals have been prepared. Many cyclic compounds that will not homopolymerize do copolymerize readily [7, 146,147]. Some cyclic compounds will copolymerize with lactones, cyclic anhydrides, or vinyl monomers. Very many commercially important materials have resulted from these copolymerizations. 

FIG. 2 IR -active functionalities on carbon surfaces (a) aromatic C=C stretching (b) and (c) carboxyl-carbonates (d) carboxylic acid (e) lactone (4-membered ring) (f) lactone (5-membered ring) (g) ether bridge (h) cyclic ethers (i) cyclic anhydride (5-metnbered ring) (j) cyclic anhydride (6-membered ring) (k) quinone (I) phenol (m) alcohol and (n) ketene. (From Ref 101.)... 

Zwitterions are spontaneously formed by reaction of nucleophilic monomers such as cyclic exo and endo imino ethers, azetidines, cyclic phosphites, and Schiff bases on the one hand, with electrophilic monomers like lactones, cyclic anhydrides, sulfones, and acrylic compounds on the other hand (Table 22-6), that is, either from two suitable heterocyclic compounds or from a heterocyclic compound and an acrylic compound. According to reaction partners, the reaction already occurs at room temperature or only after heating. 

A reaction analogous with that of cyclic-anhydride-formation is the formation of lactones from 7-hydroxy acids and from 7-halogen acids. (Cf. page 39.) A related reaction is the dehydration of acids possessing a carbonyl group in the gamma position. 

Oxidation of cyclic ethers to lactones (1, 988). A systematic study of this reaction has been reported. In general, yields are good to excellent by either stoichiometric or catalytic procedures. No anhydrides from further oxidation are detected. The oxidation is chemoselective. Oxidation of a secondary position takes precedence over oxidation of a tertiary site. Primary positions are attacked in preference to secondary positions in the oxidation of acyclic ethers.1... 

The at complex from DIB AH and butyllithium is a selective reducing agent.16 It is used tor the 1,2-reduction of acyclic and cyclic enones. Esters and lactones are reduced at room temperature to alcohols, and at -78 C to alcohols and aldehydes. Acid chlorides are rapidly reduced with excess reagent at -78 C to alcohols, but a mixture of alcohols, aldehydes, and acid chlorides results from use of an equimolar amount of reagent at -78 C. Acid anhydrides are reduced at -78 C to alcohols and carboxylic acids. Carboxylic acids and both primary and secondary amides are inert at room temperature, whereas tertiary amides (as in the present case) are reduced between 0 C and room temperature to aldehydes. The at complex rapidly reduces primary alkyl, benzylic, and allylic bromides, while tertiary alkyl and aryl halides are inert. Epoxides are reduced exclusively to the more highly substituted alcohols. Disulfides lead to thiols, but both sulfoxides and sulfones are inert. Moreover, this at complex from DIBAH and butyllithium is able to reduce ketones selectively in the presence of esters. 

The Baeyer-Villiger transformation of several protected derivatives having a free ketone group has been effected by m-chloroperoxybenzoic acid. Thus, 1,6-anhydro-3,4-0-isopropylidene-/f-D-/yxn-hexopyranos-2-ulose (28) was converted into the cyclic, orthoacid anhydride 29.67 As an additional example, the Baeyer-Villiger oxidation of Ferrier carbocyclization products derived from D-glucose afforded 5-deoxyhexofuranosiduronic acids, via the ring-expanded lactonic intermediates68 (Scheme 12). 

Block copolymers characterised by different backbone structures of well-defined block lengths have been obtained from oxiranes and other heterocyclic monomers in the presence of catalysts that are effective at bringing about living polymerisations. Aida et al. [127,188,189,195,196] applied aluminium porphyrins and Teyssie et al. [125,197,198] applied bimetallic /i-oxoalkoxidcs for block copolymerisations in systems involving oxirane lactone, oxirane oxirane/cyclic acid anhydride, and oxirane/cyclic acid anhydride lactone as block forming units and obtained respective polyether polyester and polyester polyester block copolymers. Such copolymers seem to be of exceptionally wide potential utility [53]. 

Albertsson and coworkers [240-244] carried out extensive research to develop polymers in which the polymer properties are altered for different applications. The predominant procedure is ring-opening polymerization which provides a way to achieve pure and well defined structures. They have utilized cyclic monomers such as lactones, anhydrides, carbonates, ether-lactones. The work involved the synthesis of monomers not commercially available, studies of polymerization to form homopolymers, random and block copolymers, development of cross-linked polymers and polymer blends, surface modification in some cases, and characterization of the materials formed. The characterization is carried out with respect to the chemical composition and both chemical and physical structures, the degradation behavior in vitro and in vivo, and in some cases the ability to release drug components from microspheres prepared from the polymers. 

Allene carboxylic acids have been cyclized to butenolides with copper(II) chloride. Allene esters were converted to butenolides by treatment with acetic acid and LiBr. Cyclic carbonates can be prepared from allene alcohols using carbon dioxide and a palladium catalyst, and the reaction was accompanied by ary-lation when iodobenzene was added. Diene carboxylic acids have been cyclized using acetic acid and a palladium catalyst to form lactones that have an allylic acetate elsewhere in the molecule. With ketenes, carboxylic acids give anhydrides and acetic anhydride is prepared industrially in this manner [CH2=C=0 + MeC02H (MeC=0)20]. 

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