Methyl-5-valerolactone

P-METHYL-8-VALEROLACTONE (Valeric acid, 5-hydroxy-3-methyl-, 8-lactone) 

Submitted by Raymond I. Longley, Jr., and William S. Emerson.1 Checked by T. L. Cairns and W. W. Gilbert. 

Copper chromite is prepared according to Organic Syntheses 3 and washed with sodium bicarbonate solution. The glycol is slurried with sodium bicarbonate and filtered before use. 

At this point gas evolution becomes so rapid that the temperature tends to drop slightly. 

The column is substituted for the reflux condenser in the same set-up. Stirring during distillation prevents serious bumping. 

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Nakayama, A., Kawasaki, N., Arvanitoyannis, I., lyoda, J., and Yamamoto, N., 1995, Synthesis and degradability of a novel aliphatic polyester -Poly( -methyl- -valerolactone-co-L-lactide, Po/ymer 36 1295-1301. 

Zhu and Lei reported that the neutral degradation rate of poly(DLLA-co-adipic anhydride) increased at higher content of adipic anhydride. Nakayama et reported that the addition of 20 mol% of p-methyl-valerolactone (VL) considerably increased the degradation rate of P(LLA-co-p-methyl-VL) copolymers. However, high contents of 8-valerolactone units in PLLA copolymers were found to decrease the hydrolytic degradation rate in neutral media. 

Node and coworkers have used this aromadzadon strategy for the synthesis of (-) aphanor-phineThe Diels-Alder reacdon of chiral nitroalkene, prepared by the asymmecdc nitrooleft-nation reacdon of ct-methyl-o-valerolactone, with the Danishefsky s diene followed by aromadzadon is used as a key step for this total synthesis, as shown in Scheme 8 6... 

Node and Fuji have developed a new chiral synthesis of various alkaloids using chiral nitroalkene, fS -( - -3-methyl-3-( 3 -nitrovinyl -o-valerolactone Scheme 8 11 shows a total synthesis of f-i-physosdgmine, a principM alkriloid of the CMabar bean The key nitroalkene is prepared by asymmetric nitroolefinadon of ct-methyl-o-lactone using a chirM enamine fsee... 

Bruce et al. carried out the cyclization of 4-phenylbutyric acid to tetralone in NaCl/AlCl3 (X(A1C13) = 0.68) at 180-200 °C [92]. The reaction between valerolactone and hydroquinone to give 3-methyl-4,7-dihydroxyindanone was also performed by Bruce, using the same ionic liquid and reaction conditions. These are shown in Scheme 5.1-60. 

The synthesis of 4-alkyl-y-butyrolactones 13 and 5-alkyl-<5-valerolactones 14 can be achieved in high enantiomeric excess by alkylation of ethyl 4-oxobutanoate and ethyl 5-oxopentanoate (11, n = 2, 3). The addition of diethylzinc, as well as dimethylzinc, leads to hydroxy esters 12 in high optical purity. When methyl esters instead of ethyl esters are used as substrates, the enantioselectivity of the addition reaction is somewhat lower. Alkaline hydrolysis of the hydroxy esters 12, followed by spontaneous cyclization upon acidification, leads to the corresponding y-butyro- and -valerolactones32. 

II. B polyethylene glycol, ethylene oxide, polystyrene, diisocyanates (urethanes), polyvinylchloride, chloroprene, THF, diglycolide, dilac-tide, <5-valerolactone, substituted e-caprolactones, 4-vinyl anisole, styrene, methyl methacrylate, and vinyl acetate. In addition to these species, many copolymers have been prepared from oligomers of PCL. In particular, a variety of polyester-urethanes have been synthesized from hydroxy-terminated PCL, some of which have achieved commercial status (9). Graft copolymers with acrylic acid, acrylonitrile, and styrene have been prepared using PCL as the backbone polymer (60). 

Another two ring analog of strigol was prepared in a similar manner from the sodium enolate of a-valerolactone (XXII) and XIV. There is a methyl group at the 5-position of the ring which would correspond to the C-ring of strigol, so the shorthand for this compound is Me-2-RAS (XXIII). Johnson and co-workers (21) had... 

Ring-opening polymerization of a-methyl-substituted medium-size lactones, a-methyl-y-valerolactone and a-methyl-c-caprolactone, proceeded by using lipase CA catalyst in bulk [82]. As to (R)- and (S)-3-methyl-4-oxa-6-hexa-nolides (MOHELs), lipase PC induced the polymerization of both isomers. The apparent initial rate of the S-isomer was seven times larger than that of the R-isomer, indicating that the enantioselective polymerization of MOHEL took place through lipase catalysis [83]. 

N-Methyb/>-toluenesulfonamide, 34, 97 /3-Methyl-S-valerolactone, 35, 87 Methyl vinyl ether, 34, 29 Methyl vinyl ketone, 37, 19 Michael condensation between 3-nitropro-pane and methyl acrylate, 32, 86 Monochlorourea, 30, 24, 25, 26 Monoethanolamine, 32, 19 Monoethyl malonate, 37, 34 Mucobromic acid, 32, 95... 

Levulinic acid is obtained by hydrolysis of cellulose-containing biomass. R D is actively conducted at DuPont Co. to employ levulinic acid for the synthesis of pyr-rolidones (solvents and surfactants), a-methylene-y-valerolactone [monomer for the preparation of polymers similar to poly(methyl methacrylate)], and levulinic acid esters (fuel additives) [26]. 

Reduction of lactones leads to cyclic bemiacetals of aldehydes. With a stoichiometric amount of lithium aluminum hydride in tetrahydrofuran at —10° to —15° and using the inverse technique, y-valerolactone was converted in 58% yield to 2-hydroxy-5-methyl tetrahydrofuran, and a-methyl-5-caprolac-tone in 64.5-84% yield to 3,6-dimethyl-2-hydroxytetrahydropyran [1028]. Also diisobutylaluminum hydride in tetrahydrofuran solutions at subzero temperatures afforded high yields of lactols from lactones [7024]. 

Figure 20. Simultaneous enantiomer separation of various classes of compounds ( Schurig test mixture 184) on CP-Cyclodextrin-/3-2,3,6-M-19 (permethylatcd /3-cyclodextrin in OV-1701) [25 m x 0.25 mm (i.d.) column, 70°C for 5 min followed by 3cC/miu, 0.65 bar hydrogen]143. 1+2 2,6,6-trimethylbicy-clo[3.1.1]hept-2-ene (x-pinene), 3 ( + )-(lJR)-//ms-2,6,6-trimethylbicyclo[3.1. l]heptane (pinane), 4 (-)-(lS )-fra/M-pinanc. 5 (-)-(lS)-fw-pinane, 6 ( + )-(l/J)-cw-pinane, 7 + 8 2,3-butancdiol. 9 meso-2,3-butanediol, 10 + 11 tetrahydro-5-methyl-2-furanone (y-valerolactone). 12 + 13 1-phenylethanaminc. 14 + 15 1-phenylethanol, 16 + 17 2-ethylhexanoic acid.

Some representatives of y-lactones are y-valerolactone 150, y-decalactone 151 with peach-like flavour, (Z)-6-dodecen-4-olide 152, 3-methyl-4-octanolide (whiskey lactone) 153 and 3-hydroxy-4,5-dimethyl-2(51T)-furanone (sotolone) 154 (Structure 4.46), found in fenugreek, coffee and sake [1-4, 21-23, 62]. 

There are other reactions which have been found to yield oxetanes but have not been developed as synthetic methods. The thermolysis and photolysis of y-methyl-y-peroxy-valerolactone gives 2,2-dimethyloxetane, presumably by way of a diradical intermediate (equation 87). This is the same type of intermediate involved in pyrolysis of the oxetane at a much higher temperature (71CC1299). Somewhat related are photochemical syntheses... 

LC/ESI-MS analyses were applied to determine urinary glucuronidated and sulfated tea catechins after the administration of green tea to humans, mouse and rats [109]. The major conjugates were identified as monoglucuronides and monosulfates of EGC and EC. Besides these metabolites, also G-methyl-EGC-G-glucuronides, O-sulfates and O-methyl-EC-O-sulfates in human urine were detected. Furthermore, the ring-fission metabolites of EGC and (-)-epicatechin, 5-(3 ,4 ,5 -trihydroxyphenyl)-y-valerolactone and 5-(3 ,4 -dihydroxyphenyl)- valerolactone respectively, have been detected in the monoglucuronide and monosulfate forms. 

Methyl-l-tetralone has been prepared from 7-phenylvaleric acid and sulfuric acid 8 and from 7-phenylvaleryl chloride and aluminum chloride.910 Its preparation from 7-valerolactone has not been described elsewhere. 

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