Indane 8,9-oxide

UV spectroscopy has been particularly informative about the oxepin-arene oxide ratio at room temperature (67AG(E)385) where NMR spectroscopy has been of little value (due to fast exchange processes). In order to use the UV method of analysis indane 8,9-oxide (the valence tautomer of oxepin 22) was assumed to be totally in the oxirane form while... 

Bridging substituent groups also influence the preference for either the arene oxide or the oxepin valence bond tautomer. Thus, when n = 3, indan 8,9-oxide 7 exists exclusively as the oxide form. With n = 4, tetralin 9,10-oxide 8 is dominant over its oxepin form while similar amounts of the arene oxide and oxepin are present when n = 5 (9). 

This e c o-peroxide rearranged readily to form the /ra s-benzene trioxide 144 and gave trans-benzene dioxide 142 upon reaction with triphenylphosphite. A similar addition reaction occurred between singlet oxygen and indan 8,9-oxide 7 to yield a further endo-peroxide. An endo-peroxide adduct of an oxepin was also formed when singlet oxygen reacted with 1-benzoxepin 100. Upon deoxygenation with trimethylphosphite, the latter peroxide yielded an aldehyde. ... 

Photosensitized (Rose Bengal) oxygenation of indane 8,9-oxide (5) is facile, perhaps because (5) exists entirely in the arene oxide form. The product (6) rearranges to (7) very readily. 

The Jones reagent851 and < rt-BuOOH in the presence of chromium(VI) complexes852,853 were found to be particularly useful in the oxidation of tetralins and indans. Oxidation with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) occurs with an exceptional mechanism.854 In contrast with the radical processes observed in other oxidations DDQ generates a carbocation by hydride abstraction that is trapped by water to form an alcohol ... 

In the case of 1,4-dimethylbenzene epoxide (181), incursion of intermediates like l,4-dimethyl-l,4-dihydroxydihydrobenzene (182)91,92 or intermediates like 4,8- and 4,5-indane oxides (183 and 184), respectively, by oxygen walk8,93-96 does not allow prediction of the product of epoxide opening on... 

In KYI, more than 95% of indene substrate is oxidized by a monooxygenase to indane oxide, which in turn is hydrolyzed to undesired trans-(lK,2K)-indanediol and cis-(lS,2J )-indanediol, as was verified by steady-state metabolite balancing and labeling with 14C-tracers. 

As a result of the flux analysis, the most promising target for pathway modification to augment the yield of desired trans- (lK,2K)-indanediol is enhanced selective hydrolysis of indane oxide to trans-(lR,2J )-indanediol, either by modification of the culture conditions or by overexpression of an epoxide hydrolase. 

One noteworthy example of the aromatization of an arene oxide to yield different phenols by the A h (acid-catalyzed) and ko (spontaneous) pathways is indan oxide The mechanisms for the aromatization reaction of arene oxide 7... 

Dihydrodiols have not been obtained from hydrolysis reactions of benzene oxides however, evidence for the formation of 1,4-dihydrodiols has been obtained from acid-catalysis studies on 1,4-dimethylbenzene oxide 63 ° and 8,9-indan oxide 7. The mechanism of acid-catalyzed rearrangement and hydrolysis of benzene oxide has been investigated theoretically using the semiempirical allvalence electron MINDO/3 method and the perturbational MO method, both from the viewpoint of product stabilities and reaction pathways. The aromatization reaction was found to be much more exothermic than the hydrolysis and thus would be the preferred reaction, as was found experimentally. 

Indane oxide (109) undergoes a pH-independent reaction to form 4-indanol (115), and part of this product is formed by a 1,2-alkyl migration.96 However, most of the 4-indanol is formed as a result of the isomerization of 8,9-indane oxide to 4,9-indane oxide (111) via an oxygen walk. 96a,b A minor amount of 5-indanol (116) is... 

The spontaneous oxepin-benzene oxide isomerization proceeds as a thermally allowed, disrotatory process according to the Woodward-Hoffmann rules. Because of eclipsing interactions, 2,7-substituents destabilize the benzene oxide structure and favour oxepin formation. If the 2,7-positions are bridged, the size of the bridge influences the oxepin-benzene oxide equilibrium. This is shown by studies of the 2,7-methylene-bridged systems 7 and 8 If n = 3, only the indane oxide is present if n = 4, tetrahydronaphthalene oxide predominates in the equilibrium mixture if n = 5, oxepin and benzene oxide are present in a ratio of 1 1 [4]. 

Indan oxide hydrolysis rate constant to cis-(IS,2i )-indandiol... 

C]-Metabolite concentration czs-(lS,2R)-Indandiol excretion rate czs-(lR,2S)-Indandiol excretion rate Indene uptake rate Indan oxide excretion rate l-Keto-2-hydroxy-indan excretion rate frans-(lR,2R)-Indandiol excretion rate [ -fra s-( lR,2R)-Indandiol concentration Indan oxide hydrolysis flux to czs-(lS,2R)-indandiol Dioxygenase flux Flux for enzyme i... 

Indan oxide hydrolysis flux to fraMS-(lR,2R)-indandiol... 

Protease inhibitors are well-characterized chiral drugs in terms of their mechanism of action. An important new class of protease inhibitors comprises molecules designed to treat HIV infection. In particular, indinavir sulfate (CRIXIVAN, Merck and Co., Inc.) contains five chiral centers that must be of a specific orientation for the molecule to have the desired therapeutic effect. Manufacturing processes for these compounds involving chemical synthesis steps can be quite inefficient, due to yield reduction caused by racemization at each step where a chiral center is formed. A key intermediate in the synthesis of CRIXIVAN is cis-(lS,2R)-l-amino-2-indanol [(-)-CAI], an indene derivative that contributes two chiral centers to indinavir sulfate (Fig. 1). To circumvent the technically demanding chemical synthesis of (-)-CAI and reduce product loss, Merck scientists conceptualized a bioconversion process in which indene is oxidized to one of three derivatives that can serve as precursors to (-)-CAI cis-(lS,2R)-indandiol, trans-(lR,2R)-indandiol, or (lS,2R)-indan oxide. Oxygenases that have been identified in isolates of the genus Pseudomonas and Rhodococcus can catalyze this transformation. 

Fig. 2. Indene bioconversion network in Rhodococcus strain 124 proposed by Chartrain et al. [8]. Indene is converted to the indandiol enantiomers shown through specific oxygenase activities. Dioxygenases produce the cis enantiomers of indandiol while the monooxygenase converts indene to indan oxide. The indandiols are then converted to l-keto-2-hydroxy-indan through the action of dehydrogenase enzymes and a proposed undetectable 1,2-indenediol intermediate...

A suitably designed chiral analog of NHPI can be used as an enantioselective oxidation catalyst. Einhorn reported the synthesis of axially chiral NHPI analogs (Scheme 6.21). These NHPI derivatives can be used in several catalytic asymmetric oxidation reactions, such as indane oxidation and oxidative deprotection of acetal. 

Ninhydrin (also named 1 2 3-triketoindane or 1 2 3-triketohydrindene hydrate) is prepared most simply from the inexpensive phthahc anhydride (I). The latter is condensed with acetic anhydride In the presence of potassium acetate to give phthalylacetlc acid (II) reaction of the latter with sodium methoxide in methanol yields 1 3-indanedionecarboxyhc acid, which is decomposed upon warming with dilute hydrochloric or sulphuric acid to indane-1 3-dione (or 1 3-diketohydrindene) (HI). Selenium dioxide oxidation of (III) afibrds indane-1 2 3-trione hydrate (ninhydrin) (IV). 

Gumylphenol. -Cumylphenol (PGP) or 4-(1-methyl-l-phenylethyl)phenol is produced by the alkylation of phenol with a-methylstyrene under acid catalysis. a-Methylstyrene is a by-product from the production of phenol via the cumene oxidation process. The principal by-products from the production of 4-cumylphenol result from the dimerization and intramolecular alkylation of a-methylstyrene to yield substituted indanes. 4-Cumylphenol [599-64-4] is purified by either fractional distillation or crystallization from a suitable solvent. Purification by crystallization results in the easy separation of the substituted indanes from the product and yields a soHd material which is packaged in plastic or paper bags (20 kg net weight). Purification of 4-cumylphenol by fractional distillation yields a product which is almost totally free of any dicumylphenol. The molten product resulting from purification by distillation can be flaked to yield a soHd form however, the soHd form of 4-cumylphenol sinters severely over time. PGP is best stored and transported as a molten material. 

The catalytic system used in the Pacol process is either platinum or platinum/ rhenium-doped aluminum oxide which is partially poisoned with tin or sulfur and alkalinized with an alkali base. The latter modification of the catalyst system hinders the formation of large quantities of diolefins and aromatics. The activities of the UOP in the area of catalyst development led to the documentation of 29 patents between 1970 and 1987 (Table 6). Contact DeH-5, used between 1970 and 1982, already produced good results. The reaction product consisted of about 90% /z-monoolefins. On account of the not inconsiderable content of byproducts (4% diolefins and 3% aromatics) and the relatively short lifetime, the economics of the contact had to be improved. Each diolefin molecule binds in the alkylation two benzene molecules to form di-phenylalkanes or rearranges with the benzene to indane and tetralin derivatives the aromatics, formed during the dehydrogenation, also rearrange to form undesirable byproducts. 

Shah et al. (1994) have studied the preparation of a class of compounds called Indans, by cross-dimerization of AMS with amylenes, using an ion-exchange resin and acid-treated clay catalysts (Eqns. (12) and (13)). Indans can be subsequently converted, e.g. by acetylation, into perfumric compounds having mu.sk odour. For example, 1,1,2,3,3-pentamethylindan, the product obtained by cross-dimerization of AMS and wo-amylene (Eqn. (12)), can be reacted with propylene oxide and /7 ra-formaldehyde to give an indan type isochroman musk compound, 6-oxa-l,l,2,3,3,8-hexamethyl-2,3,5,6,7,8-hexahydro-lH-benz(f)-indene, sold as Galaxolide commercially. 

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