Tetraline derivatives

Dihydioxytetiahydionapthacenedione derivatives, used as intermediates for the anthracycline antibiotics have been prepared by Friedel-Crafts reaction of tetralin derivatives with orthophthaloyl chlotide [88-95-9J in high yields (93). 

There are many examples in the literature of the exchange of aromatic hydrogens in benzene, naphthalene and tetralin derivatives which employ... 

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. 

The retrosynthetic concept of the Nicolaou group is shown in Scheme 22. The target molecule 36 is disconnected via an IMDA cyclization of the diene quinone precursor 138, which would be generated from the tetraline derivative 139 using Wittig chemistry followed by aromatic oxidation. A Claisen-type rearrangement would provide access to 139 whereby the side chain required for the rearrangement of 140 would be introduced by 0-acylation. The core of 141 would be formed via an intermolecular Diels-Alder reaction between diene 142 andp-benzoquinone 130 [42]. 

The regioselectivity of these ring opening reactions is sensitive to additional annelation on benzene (Table 7). In the tetralin derivative (59), little selectivity between type I and type II products is observed with either set of electrophilic reagents. A reversal of regioselectivity is observed in cyclobutabenzene and indan... 

Phenylalkenes also undergo intramolecular alkylation under Friedel-Crafts conditions to yield five- or six-membered cyclic products (indan or tetralin derivatives, respectively). This cyclialkylation145,146,175 may actually also be considered as an isomerization reaction. 

When cycloalkanes (cyclopentane, cyclohexane) alkylate benzene, cycloalkylben-zenes, as well as bicyclic compounds (indan and tetralin derivatives) and products of destructive alkylation, are formed.191192 Cyclohexane reacts with the highest selectivity in the presence of HF—SbF5 to yield 79% cyclohexylbenzene and 20—21% isomeric methylcyclopentylbenzenes.191... 

He considered as mono-aromatics molecules with one or more non-condensed benzene nuclei, e.g. alkyl-benzenes, tetralin-derivatives, diphenyl. Di-aromatics he defined as molecules with one or more naphthalene nuclei not condensed with each other or with a benzene nucleus. 

A range of diols and cyclic ethers were used to carry out alkylation of aromatics (benzene, toluene, xylenes, trimethylbenzenes, naphthalene) in the presence of triflic acid.204 310 In a recent study,311 various methyl-substituted benzene derivatives were alkylated with 1,4-diols [Eq. (5.117)] to form substituted tetralin derivatives in high yields. The transformations involve an intermolecular alkylation step followed by intramolecular alkylation (cyclialkylation). 2,2,5,5-Tetramethyltetrahydrofuran is similarly effective. For example, it alkylates benzene to give octamethyloctahydroan-thracene (98% yield) and reacts with naphthalene to yield octamethyloctahydrote-tracene [Eq. (5.118)]. 

Hirano et al. reported on the stereoselective cyclization to give tetralin derivatives using the phenanthrene-p-dicyanobenzene sensitizer system. Pandey independently reported the intramolecular photocyclization of methoxybenzene derivatives bearing silyl enol ether chromophore via their heterodimer radical cations in the presence of 1,4-dicyanonaphthalene gave benzo-annulated cyclic ketones in 70% yields [490] (Scheme 133). 

An interesting comparison can be made looking at the a- and (5-tetralin derivatives entries—15/16 and —17 in Table 1 which can be regarded as cyclic confor-mationally constrained analogues of phenylglycine and phenylalanine. In an interesting study, 6-hydroxy-2-aminotetralin-2-carboxylic acid 12 (Hat) has been incorporated as a conformationally constrained tyrosine analogue into S-opioid receptor selective tetrapeptides.114 15 Whereas entry 15, the (S)-a-tetralin deriva-... 

In peptide 32, which has an (/ )-a-tetralin derivative at position 2, we observed one 310-helical turn at the N-terminus with an exclusive H-bond between the Boc carbonyl group and the NH (i+3). The rest of the molecule adopts a a-helical backbone conformation (mean values = -62°, = -40°). The amino group of... 

Oxetanes have also been used as alkylating agents in the Friedel-Crafts reaction for example, 2-isopropyloxetane was reacted with benzene in superacidic trifluoromethanesulfonic acid (TFSA) to give a mixture of alkylated aromatic products (Equation 9) <2003CAL1>. The main product of the reaction was the tetralin derivative 46 which could be isolated in up to 75% yield. Other notable side products are shown, resulting from monoalkylation or other skeletal rearrangements. 

Dopamine receptors may occur on the terminals of the glutamatergic afferents to the neostriatum (63). Following cortical ablation, the number of 3H]-haloperidol binding sites in the striatum is reduced by 32% (63). In an in vitro superfusion system, dopamine, apomorphine, amino tetralin derivatives or bromocriptine inhibit the depolarization-induced release of... 

The use of co-(2-bromophenyl)alkyl-2-oxazolines (13) in base-promoted ring-closure reactions provides a good access to 1-phenyl-indane and 1-phenyl-tetralin derivatives (14) that contain easily manipulated oxazoline moieties. Satisfactory isolated yields of cyclized products 14 are obtained with lithium diisopropylamide (LDA) in THF at room temperature under irradiation with UV light, even when quaternary centers are formed (Scheme 10.39) [55]. The yield of 14 (n= 1, R= Ph) increases to 75% when the reaction proceeds under laboratory light for 48 h at room temperature. 

As Shibasaki and co-workers demonstrated, tetralin derivatives of type 55 (with a quaternary benzylic carbon center) can also be enantioselec-tively prepared by an intramolecular Heck reaction (Scheme 14) [19]. 

This type of cyclization is not limited to propanediones but has also been observed with ortho substituted benzils104) and with tetralin derivative 149. In the latter case, a cyclic sulfone was also obtained in quantitative yield. 

Polycyclic musk fragrances (PMFs) are indane and tetraline derivatives with different substituents [361 a]. These chemicals with strong musk odor are used as fragrances in cosmetics and laundry detergents and are of great industrial importance. According to a study of the fragrance industry in 1987 the world-... 

Synthetically, compound 152 was prepared by the Friedel-Crafts procedure from furan-3,4-dicarbonyl chloride and a tetralin derivative (85JCR (S)338). 1,4-Dihydro-l,4-epoxy-5,8-naphthoquinone, when treated with 3,6-di(2-pyridyl)-l,2,4,5-tetrazine, yielded the quinone 153 (75JCS(P1)1339) derivatives of 153 are also known (74CC1034). The parent compound (153) is a stable derivative of the unstable isobenzofuran. Finally, 3-acetyl-2-furyl-1,4-benzo- (or -naphtho-) quinones are isomerized photochemically in aprotic solvents into the quionones 154 (66HCA1806). 

There are a few tetra- and pentacyclic analogues. Benzo analogues of 245 were prepared from pyridine-2,3-dicarboxylic acid anhydride and a tetralin derivative under conditions of the Friedel-Crafts reaction (85JCR(S)338). Pentacyclic compounds 258 (R = H or Me) were prepared from the bis adduct of anthranilic (or IV-methylanthranilic) acid to 1,4-benzoquinone, followed by cyclization in concentrated sulfuric acid (55JCS4440 66CB1991). 6-Methylquinoline-5,8-dione dimerized in the presence of ethanolic N-methyl-cyclohexylamine to 259 in very low yield and the dimerization is interpreted as two base-catalyzed addition reactions and three oxidation steps (71JCS(C)1253). 

Synthesis of a tetracyclic analog of 294 is also reported from the anhydride of pyrazine-2,3-dicarboxylic acid and a tetralin derivative under Friedel-Crafts conditions (85JCR(S)338). A representative of the o-quinonoid system (296) was prepared from 2,3-dichloro-1,4-naphthoquinone and o-phenyl-enediamine (63JOC1019). 

Cycloalkylations with primaiy and secondary phenylalkyl chlorides are often accompanied by rearrangements. The ease of formation of a six-membered ring (tetralin derivative) is much greater than that of a five-membered ring (indane derivative), based on entropy and strain factors. Khalaf and Roberts have performed stereochemical studies on cycloalkylation reactions to determine the effect of stereochemistry and steric factors in the formation of six-membered rings. 

Buchanan et alP" conducted model studies on the hydrocracking of coal by studying in detail the action of SbCb melts with (and in some cases without) AlCb on a,(i>-diphenyialkanes. They observed selective sp sp bond cleavage for the four classes of diphenylalkanes studied, as shown in equations (116) to (118). Notably, 1,3-diphenylpropane and 1,4-diphenylbutane gave only the indan and tetralin derivatives, respectively. 

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