Indene epoxidation

Alternatively, Sepracor scientists employed the enantiomeric catalyst (R,R)-71 to epoxidize indene with NaOCl in dichloromethane to give (1 R,2S)-72. This was ring-opened with ammonia and transformed into oxazoline 74 by reaction with benzoylchloride in Schot-ten-Baumann conditions followed by addition of 80% sulfuric acid. Hydrolysis of 74 afforded 73. 

Jerina e( al. (1968) have shown that an epoxide hydrase of rabbit liver microsomes, or the. soluble fraction of liver homogenate, convert benzene epoxide to the dihydrodiol (see Fig. 4). The reaction was also demonstrated with styrene epoxide, indene epoxide, and cyclohexene epoxide. A soluble dehydrogenase from the liver preparation oxidized dihydrodiols to catecliols. The conversion of the epoxide to phenol was considered to be a nonenzymic isomerization. In the presence of glutathione and glutathione-iS-epoxide transferase, a glutathione conjugate was formed. 

Such copolymers of oxygen have been prepared from styrene, a-methylstyrene, indene, ketenes, butadiene, isoprene, l,l-diphen5iethylene, methyl methacrjiate, methyl acrylate, acrylonitrile, and vinyl chloride (44,66,109). 1,3-Dienes, such as butadiene, yield randomly distributed 1,2- and 1,4-copolymers. Oxygen pressure and olefin stmcture are important factors in these reactions for example, other products, eg, carbonyl compounds, epoxides, etc, can form at low oxygen pressures. Polymers possessing dialkyl peroxide moieties in the polymer backbone have also been prepared by base-catalyzed condensations of di(hydroxy-/ f2 -alkyl) peroxides with dibasic acid chlorides or bis(chloroformates) (110). 

Oxaziridines unsubstituted at nitrogen as well as some iV-acylated oxaziridines offer synthetic potentialities due to their ability to transfer their nitrogen function to nucleophiles (Section 5.08.3.1.4). The simplicity of preparation of some aziridines from alkenes and the Spiro oxaziridine (S2) equals the simplicity of epoxidation. Aziridine (299), for example, is obtained by simple heating of indene with (52) in toluene (74KGS1629). 

The epoxidation method developed by Noyori was subsequently applied to the direct formation of dicarboxylic acids from olefins [55], Cyclohexene was oxidized to adipic acid in 93% yield with the tungstate/ammonium bisulfate system and 4 equivalents of hydrogen peroxide. The selectivity problem associated with the Noyori method was circumvented to a certain degree by the improvements introduced by Jacobs and coworkers [56]. Additional amounts of (aminomethyl)phos-phonic acid and Na2W04 were introduced into the standard catalytic mixture, and the pH of the reaction media was adjusted to 4.2-5 with aqueous NaOH. These changes allowed for the formation of epoxides from ot-pinene, 1 -phenyl- 1-cyclohex-ene, and indene, with high levels of conversion and good selectivity (Scheme 6.3). 

Compounds lb and 2b were the Urst fluorinated ligands tested in Mn-catalyzed alkene epoxidation [5,6]. The biphasic Uquid system perfluorooc-tane/dichloromethane led to excellent activity and enantioselectivity (90% ee) in the epoxidation of indene with oxygen and pivalaldehyde (Scheme 1, Table 1). In addition, the fluorous solution of the catalyst was reused once and showed the same activity and selectivity. This represents a considerable improvement over the behavior in the homogeneous phase, where the used catalyst was bleached and reuse was impossible. Unfortunately, indene was the only suitable substrate for this system, which failed to epoxidize other alkenes (such as styrene or 1,2-dihydronaphthalene) with high enantioselectivity. The system was also strongly dependent on the oxidant and only 71% ee was obtained in the epoxidation of indene with mCPBA at - 50 °C. 

Asymmetric epoxidation of indene as a step in making the HIV Davies and Reider... 

Davies and Reider (1996) have given some details of the HIV protease inhibitor CRDCIVAN (INDINAVIR) for which (lS,2R)-c -amino indanol is required. Indene is epoxidized enantioselectively, using the lacobsen strategy (SS-salen Mn catalyst, aqueous NaOH and PiNO), to (lS,2/ )-indene oxide in a two-phase system, in which the OH concentration is controlled. Indene oxide was subjected to the Ritter reaction with MeCN, in the presence of oleum, and subsequent hydrolysis and crystallization in the presence of tartaric acid gives the desired amino indanol. 

More subtle arguments have been invoked to rationalize the dichotomous behavior of so-called second-generation Mn-salen catalysts of type 7 toward unfunctionalized and nucleophilic olefins. For example, higher yields and ee s are obtained with the (i ,S)-complex for the epoxidation of indene (8). However, JV-toluenesulfonyl-l,2,3,4-tetrahydropyridine (10) gave better results using the (R,/ -configuration. An analysis of the transition-state enthalpy and entropy terms indicates that the selectivity in the former reaction is enthalpy driven, while the latter result reflects a combination of enthalpy and entropy factors <00TL7053>. 

A typical manganese-salen complex (27)[89] is capable of catalysing the asymmetric epoxidation of (Z)-alkenes (Scheme 18) using sodium hypochlorite (NaOCl) as the principle oxidant. Cyclic alkenes and a, (3-unsaturated esters are also excellent starting materials for example indene may be transformed into the corresponding epoxide (28) with good enantiomeric excess1901. The epoxidation of such alkenes can be improved by the addition of ammonium acetate to the catalyst system 911. 

Bromine-atom atomic resonance absorption spectrometry (ARAS) has been applied to measure the thermal decomposition rate constants of CF3Br in Kr over the temperature range 1222-1624 K. The results were found to be consistent with recently published theory. The formation of cyclopent[a]indene and acenaphthylene from alkyl esters of biphenyl-mono- and -di-carboxylic acids has been observed in flash vacuum pyrolyses at 1000-1100 °C. The kinetics and mechanisms of free-radical generation in the ternary system containing styrene epoxide, / -TsOH, and i-PrOH have been examined in both the presence and absence of O2. ... 

Synonyms AI3-25584 EINECS 213-831-0 ENT 25584 Epoxy heptachlor HCE HE (3-Heptachlor epoxide Heptachloro epoxide l,4,5,6,7,8,8-Heptachloro-2,3-epoxy-2,3,3a,4JJa-hexahydro-4,7-methanoindene l,2,3,4,5,6,7,8,8-Heptachloro-2,3-epoxy-3a,4,7,7a-tetrahydro-4,7-methanoindene 5a,6,6a-Hexahydro-2,5-methano-2/f-indeno[l,2-A]oxirene 2,3,4,5,6,7,7 Hep tachloro-la,lb,5,5a,6,6a-hexahydro-2,5-methano-2//-oxireno[a]indene UN 2761 Velsicol 53-CS-17. 

Heptachloro-la, lb,5,5a,6.6a-hexahydro-2,5-methano-27/-oxireno[a]indene, see Heptachlor epoxide... 

Heptachloro-3a,4,7,7a-tetrahydro-4,7-methano-l/7-indene see Chlordane Heptachlor triol, see Heptachlor epoxide Heptanal, see Heptane. 1-Octene 1-Fleptanol. see Heptane Heptanoic acid, see Heptane 1-Fleptene. see Heptane Heptyl hydroperoxide, see Heptane Hexachlorobenzene, see Hexachlorobutadiene,... 

For 2,2-disubstituted epoxides 68a-d bearing a 2-phenyl substituent, their corresponding catalytic cyclizations gave good yields of l-phenyl-2-methyl-lH- indenes 69a-c using the same ruthenium catalyst under similar conditions [25]. It is interesting to note that the same product 69c vas obtained for different epoxides 68c and 68d, bearing a fiuoro substituent at their phenyl C4 and C5, respectively. 

Enantiomerically pure epoxides and diols, readily available through the asymmetric epoxidation and asymmetric dihydroxylation reactions, are ideal precursors to prepare cis-amino alcohols via the Ritter reaction. " " A Merck group has shown that indene oxide 175a can be converted effectively to c/i-l-amino-2-indanol, a key fragment of the HlV-protease inhibitor Indinavir via the cis-... 

A one-step synthesis of isochromene itself has been reported from indene oxide (191) (66CC415). Irradiation of the epoxide in benzene affords two products, isochromene and indan-2-one, in similar quantities. It was proposed that initial fission of the carbon-carbon bond of the three-membered ring is followed by 1,4- or 1,2-hydrogen migration (Scheme 36). 

On the other hand, indene oxide and 1,2-epoxytetralin (Eq. 327). undergo reduction with no difficulty on treatment with sodium in moist ether. . n i The phenyl ring not only greatly enhances the eufioeptibility of the epoxide function to attack by hydrogen, but also directs addition exclusively to the benzylie portion. Similar results were obtained when reduction was conducted with sodium in liquid ammonia.1 ... 

Epoxides derived from indene,21 1,2- and 1,4-dihydronaphtha lenc 1702 a,4-benzo-1,S cycloheptadicne, 68 and 3,4-benzo-l,3-cycIo-octodlene841 are a)) reported to undergo isomerization to ketones in the presence of magnesium bromide (Eq. 450). That the carbonyl function is separated in every instance from the benzene ring by a methylene group may be taken to indicate probable existence of an open car-bonium ion in these processes. Bing contraction has been noted in one... 

Lactone formation on treatment of uneatumted acids with pwox acids ib not confined to the field of fatty acid chemistry. Howell m l Taylor obtained a hydroxylactone, for instance, on adding perfoi nm acid to the indene derivative shown in Eq. 1 106). An epoxide < assumed to constitute the intermediate stage of this transformation. 

In a similar manner, thiophonol has been condensed with etbyleno oxide itself,1230 with cyclohexene oxide,1230 and more recently with indene oxide.684 The last undergoes addition preferentially at the henscylic epoxide carbon atom Both alicyclic epoxides (Eqs. 663 and 664) are cleaved to 2-phenylthiocycloalkanols possessing fazna-con-figuration. 

Heptachlor [76-44-8] or l,4,5,6,7,8,8-heptachloro-3, 4,7,7 -tetrahydro-4,7-methano-lff-indene (33) (mp 95°C, vp 0.04 Pa at 25°C), is soluble in water to 56 //g/L. It is about 3—5 times more active than chlordane as an insecticide. The rat LD5Qs are 100, 162 (oral) and 195,250 (dermal) mg/kg. Heptachlor is oxidized readily to heptachlor epoxide [1024-57-3] (mp 159°C), rat oral LD5Q 47 mg/kg, which is an important and highly persistent environmental pollutant. Hydrogenation of heptachlor produces p-dihydroheptachlor [14168-01-5] (mp 135°C), which retains high insecticidal activity with very low mammalian toxicity, rat oral LD50 >5000 mg/kg. 

Manoj KM, Lakner FJ, Hager LP (2000) Epoxidation of Indene by Chloroperoxidase. J Mol Catal B Enzym 9 107... 

The stereochemistry of the CPO-catalyzed epoxidation of indene has been reported [279]. In aqueous solution the initially formed epoxide is not stable and opens to form the ds-diols. When the reaction is carried out in the absence of water, the epoxide enantiomers were isolated, with the lS,2f -enantiomer being formed in 30% ee (Scheme 2.24). 

R. D. Larsen, T. R. Verhoeven, and P. J. Reider, Mechanistic study of the Jacobsen asymmetric epoxidation of indene,/. Org. Chem. 1997, 62, 2222-2229. International Conference on Harmonisation Guidance on Q A Specifications Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products, Chemical Substances. Federal Register 2000, December 29, 65(251), Notices Food and Drug Administration [Docket No. 97D-0448],... 

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