Lactones y-butyrolactone

Five-membered unsubstituted lactone, y-butyrolactone (y-BL), is not polymerized by conventional chemical catalysts. However, oligomer formation from y-BL was observed by using PPL or Pseudomonas sp. lipase as catalyst. Enzymatic polymerization of six-membered lactones, 8-VL and l,4-dioxan-2-one, was reported. 8-VL was polymerized by various lipases of different origins. The molecular weight of the enzymatically obtained polymer was relatively low (less than 2000). 

Five-membered unsubstituted lactone, y-butyrolactone, is not polymerized by conventional chemical catalysts. On the other hand, oligomer formation from y-butyrolactone was observed by using PPL or Pseudomonas sp. lipase as catalyst [23,69]. 

Lactones (cyclic esters) undergo anionic and cationic polymerization to form polyesters (Eq. 7-75) [Duda and Penczek, 2001 Johns et al., 1984 Kubisa, 1996 Lundberg and Cox, 1969 Young et al., 1977]. The reactivity of different lactones generally follows the pattern for other cyclic monomers, except that the 5-membered lactone (y-butyrolactone) does... 

Five-membered lactones (y-butyrolactones) fused to carbohydrates have proven to be convenient synthons towards branched-chain sugars through opening of the lactone unit. Velaskes et al. [208] described the synthesis of y-butyrolactones... 

S. Velazquez, S. Huss, and M.-J. Camarasa, Stereoselective synthesis of [3.3.0] fused lactones (y-butyrolactones) of sugars and nucleosides by free radical intramolecular cyclization, J. Chem. Soc. Chem. Commun. p. 1263 (1991). 

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. 

G.l) (G.l) 2(3//)-Furanone dihydro-, butano-4-lactone, tetrahydrofuran-2-one, 4-butanolide, 4-hydroxybutanoic acid lactone, y-butyrolactone 196-48-0] FEMA 3291... 

Esters such as ethylcaproate, ethylbenzoate, phenylbenzoate and lactones, y-butyrolactone, and phthalide utilize 2 equiv of hydrides. Esters are reduced to the corresponding alcohols, while lactones afford the diols in almost quantitative yield. 

Five-membered, unsubstituted, lactone y -butyrolactone (y-BL) was polymerised by PPL or PCL [74, 81] into small oligomers with a DP of 8-11. More recently, y-BL have yielded homopolymers of up to 50,000 [82]. Poly(y-butyrolactone) is a very useful biomaterial, since its degradation gives y-hydroxybutyric acid, a metabolite naturally occurring in the body. In the PSL-catalysed polymerisation of y-valerolactone (y-VL) and y-caprolactone (y-CL), less than 10% conversion was observed at 60 °C for 480 h [76]. 

The five-membered unsubstituted lactone y-butyrolactone (y-BL) may not polymerize when using a conventional chemical catalyst. However, it was reported that only an oligomer was produced by the ring-opening polymerization of y-BL using PPL or lipase from Pseudomonas sp. [11,36]. 

The elucidation of the mechanism of ring-opening copolymerization of cyclic urea and carbonates offered opportunihes to study the general applicability of this mechanism to the copolymerizahon of tetramethylene urea with other monomers. The five-membered lactone, y-butyrolactone, is a readily available and cheap monomer, which may barely be homopolymerized (see Chapter 11). The copolymerization of tetramethylene urea with y-butyrolactone in the presence of dibutyl-magnesium as catalyst in the melt at 100 °C resulted in an alternating poly(amide urethane) (M = 12 600gmoT M = 21000gmoT = 1.67) [64]. 

Indoles can also be alkylated by lactones[l4]. Base-catalysed reactions have been reported for (3-propiolactone[15], y-butyrolactone[10] and 5-valerolac-tone[10]. These reactions probably reflect the thermodynamic instability of the N -acylindole intermediate which would be formed by attack at the carbonyl group relative to reclosure to the lactone. The reversibility of the JV-acylation would permit the thermodynamically favourable N-alkylation to occur. 

These trivial names are permitted -y-butyrolactone, -y-valerolactone, and 5-valerolactone. Names based on heterocycles may be used for all lactones. Thus, -y-butyrolactone is also tetrahydro-2-furanone or dihydro-2(3/f)-furanone. 

Other methods include ring opening of parasorbic acid [108-54-3] (5-lactone of 5-hydroxy-2-hexenoic acid) in hydrochloric acid or in alkaline solutions (43,44), the ring opening of y-vinyl- y-butyrolactone in various catalysts (45,46), or isomerization of 2,5-hexadienoic acid esters (47,48). Other methods are described in thehterature (6,49,50). 

Reaction with Lactones. Hydroxycarboxyhc acid ester complexes of titanium are formed by reaction of a tetraalkyl titanate with a lactone, such as P-propiolactone, y-butyrolactone, or valerolactone (35). For example. 

Results of fluorination of lactones with sulfur tetrafluoride depend on the ring size. y-Butyrolactone undergoes ring cleavage to give y-fluorobutyryl fluoride, which IS further fluormated to 1,1,1,4-tetrafluorobutane. The six-membered 1,4-di-... 

Perfluoro-y-butyrolactone can be prepared from 1,4 diiodoperfluorobutane by reaction with turning sulfuric acid (oleum) [7S] (equation 19) The yield depends on the concentration of sulfur trioxide One of the by-products, 4-iodoperfluo-robutyryl fluoride, can be recycled to increase the overall yield of the lactone Pure sulfur trioxide generates only perfluorotetrahydrofuran, the lodo acyl fluoride, and perfluorosuccmyl fluoride... 

The use of an ester as an anion-stabilizing group for a lithiated epoxide was demonstrated by Eisch and Galle (Table 5.5, Entry 11). This strategy has been extended to a,P-epoxy-y-butyrolactone 191, which could be deprotonated with LDA and trapped in situ with chlorotrimethylsilane to give 192, which was used in a total synthesis of epolactaene (Scheme 5.45) [69], The use of a lactone rather than a... 

Homoenolate Reactivity The ability to generate homoenolates from enals and its application to the preparation of y-butyrolactones 30, through reaction with an aldehyde or aryl trifluoromethyl ketone, was reported independently by Glorius [8], and Bode and Burstein [9] (Scheme 12.4). A sterically demanding NHC catalyst is required to promote reactivity at the d terminus and to prevent competitive benzoin dimerisation. Nair and co-workers have reported a similar spiro-y-lactone formation reaction using cyclic 1,2-diones, including cyclohexane-1,2-dione and substituted isatin derivatives [10]. 

Zhang68 has applied the cyclization of esters to the formation of a-methylene-y-butyrolactones, thus offering a novel and enantioselective entry to these substructures. The importance of this unsaturated lactone is evidenced by its ubiquitous presence in nearly a third of all naturally occurring secondary metabolites. The Alder-ene reaction has been applied to a formal total synthesis of (+)-pilocarpine, a leading therapeutic reagent for the treatment of narrow and wide glaucoma. Zhang intersected Btichi s synthetic intermediate (i )-181 (Scheme 47) in only two steps with a 99% ee and a 91% overall yield. In comparison, Biichi synthesized (i )-181 in five steps with a 92% ee and a 20% overall yield. 

Mitsubishi have reported several processes based on Ru-catalyzed hydrogenation of anhydrides and acids. Succinic anhydride can be converted into mixtures of 1,4-butane-diol and y-butyrolactone using [Ru(acac)3]/trioctylphosphine and an activator (often a phosphonic acid) [97]. Relatively high temperatures are required ( 200°C) for this reaction. The lactone can be prepared selectively under the appropriate reaction conditions, and a process has been developed for isolating the products and recycling the ruthenium catalyst [98-100]. 

Limited progress has been achieved in the enantioselective hydrogenation of a,/ -unsaturated carboxylic acid esters, amides, lactones, and ketones (Scheme 26.10). The Ru-BINAP system is efficient for the hydrogenation of 2-methy-lene-y-butyrolactone, and 2-methylene-cyclopentanone [98]. With a dicationic (S)-di-t-Bu-MeOBIPHEP-Ru complex under a high hydrogen pressure, 3-ethoxy pyr-rolidinone could be hydrogenated in isopropanol to give (R)-4-ethoxy-y-lactam in 98% ee [39]. 

Similarly, 5-lactols and 5-lactones are obtainable from the corresponding homo allylic alcohols. With dehydration, the corresponding dihydropyrans are prepared. Spirocyclic y-butyrolactones of this type and the corresponding 5-lactones are widespread in nature and play a key role as synthetic intermediates. 

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