Tetralones dehydrogenation

The most important process to produce 1-naphthalenol was developed by Union Carbide and subsequently sold to Rhc ne-Poulenc. It is the oxidation of tetralin, l,2,3,4-tetrahydronaphthalene/719-64-2] in the presence of a transition-metal catalyst, presumably to l-tetralol—1-tetralone by way of the 1-hydroperoxide, and dehydrogenation of the intermediate ie, l-tetralol to 1-tetralone and aromatization of 1-tetralone to 1-naphthalenol, using a noble-metal catalyst (58). 1-Naphthol production in the Western world is around 15 x 10 t/yr, with the United States as the largest producer (52). 

The salicylic acid functionality incorporated in a rather complex molecule interestingly leads to a compound that exhibits much the same activity as the parent. The 1,4 diketone required for formation of the pyrrole ring can be obtained by alkylation of the enamine from 2-tetralone (38) with phenacyl bromide. Condensation of the product, 39, with salicylic acid derivative 40 leads to the requisite heterocyclic system (41). The acid is then esterified (42) and the compound dehydrogenated to the fully aromatic system (43). Saponification affords fendosal (44). ... 

Phenylnaphthalene has been prepared by the reaction of a-halonaphthalenes with mercury diphenyl3 6 or with benzene in the presence of aluminum chloride,6 and by means of the Gri-gnard synthesis, starting with either bromobenzene, cyclohexyl chloride, and a-tetralone 7 or with a-bromonaphthalene and cyclohexanone.6 8 9 Dehydrogenation of the reduced naphthalene has been accomplished by the use of sulfur,6 bromine,8 platinum black, or selenium.7 The formation of the hydrocar-... 

Tetrachloroethane, purification of, 176 Tetradecanoic acid, 938, 940, 941 n-Tetradecyl bromide, 283 1 2 3 4-Tetrahydrocarbazole, 852 Tetrahydrofuran, 271 Tetrahydrofurfuryl chloride, 896, 901 Tetrahydropyran, 271 Tetralin, dehydrogenation of, 948, 949 purification of, 949 a-Tetralone, 728, 737 Tetramethyl base, 987 pp -Tetramethyldiaminodiphenyl-methane, 987... 

The Vilsmeier-Haack reaction of ketones forms chlorovinyl aldehydes, which can add thiols readily. The reaction with a-tetralone gave the chlorovinyl aldehyde (230), and reaction with ethyl thioglycolate in ethanolic ethoxide solution formed the dihydro derivative (231), easily dehydrogenated to naphtho[l,2-6]thiophene-2-carboxylate (73JCS(P1)2956). 

Alkyl- or aryl-dibenzothiophenes are conveniently prepared from the 2-arylthio-cyclohexanones, which are readily cyclized and dehydrogenated to yield the respective 1-, 2-, 3- or 4-substituted dibenzothiophenes (382 equation 9 Section 3.15.2.3.2). More complex polycyclic systems are available, using suitable aryenethiols, such as naph-thalenethiols, and 2-bromo-l-tetralone to synthesize the appropriate 2-arylthio ketones. Diaryl sulfides can be converted to dibenzothiophene derivatives in satisfactory yields by photolysis in the presence of iodine (equation 10) (75S532). Several alkyldibenzothiophenes with substituents in the 2- and/or 3-positions were prepared in satisfactory yield by the condensation of dichloromethyl methyl ether with substituted allylbenzo[6]thiophenes (equation 11) (74JCS(P1)1744). 

Aryl nitriles The most satisfactory route to the naphthalenecarbonitrile 3 is addition of (CH3)3SiCN to the 1-tetralone 1 followed by conversion to the a,(l-unsuturated nitrile 2. Dehydrogenation to the fully aromatic nitrile can be effected with DDQ, but is effected preferably with palladium-on-charcoal in combination with sulfur. 

Methoxy-a-tetralone (137), which on formylation at room temperature followed by treatment with n-butanethiol in presence of p-toluenesulfonic acid gave the compound (138), which was converted with lithium dimethylcopper and acetic anhydride to (139). Subjection of (139) to dehydrogenation, hydrolysis and methylation, respectively, yielded (140) which was converted to tetralone (141) by reduction, hydrolysis and methylation of pyralidine enamine. Alkylation of (141) with 2-... 

The enamide 73 was prepared from 2,3-dimethoxy-5,6-methylenedioxy-benzoic acid and 6,7-methylenedioxy-l-tetralone, and was then irradiated to afford the lactam 74 in 38% yield. On acid treatment 74 was converted to the dehydrolactam 75 as a result of the elimination of the migrated meth-oxyl group. Dehydrogenation with 30% Pd/C, reduction with vitride, followed by treatment with DDQ, completed total synthesis of chelirubine (76) 91,92) (Scheme 43). 

Crawford and co-workers " discovered a surprising combination for effecting dehydrogenation palladium charcoal and sulfur. The Diels-Alder adduct (3) was obtained by pinacol reduction of the tetralone (1), dehydration to (2) by refluxing... 

An alternative approach to the tetracyclic systan forms the heterocyclic ring by nucleophilic addition of an amine to a carbonyl group. Application of the Friedlander quinoline synthesis to various methoxy-1-tetralones yields the methoxy-5,6-dihydrobenz-[c]acridines, which are dehydrogenated to the aromatic compound by distillation from palladium-charcoal (M. Croisy-Delcey et al. J. med. Chem., 1983, 26, 303). 

There are two main synthetic routes to naphthalene the Haworth synthesis and a Diels-Alder approach. In the Haworth synthesis (Scheme 12.1), benzene is reacted under Friedel-Crafts conditions with succinic anhydride (butanedioic anhydride) to produce 4-oxo-4-phenylbutanoic acid, which is reduced with either amalgamated zinc and HCl (the Clemmensen reduction) or hydrazine, ethane-1,2-diol and potassium hydroxide (the Wolff-Kischner reaction) to 4-phenylbutanoic acid. Ring closure is achieved by heating in polyphosphoric acid (PPA). The product is 1-tetralone and reduction of the carbonyl group then gives 1,2,3,4-tetrahydronaphthalene (tetralin). Aromatization is achieved by dehydrogenation over a palladium catalyst. 

Note that palladised charcoal has also been used for dehydrogenation, e.g. tetralin is converted to naphthalene by boiling for 4 honrs in the presence of Pd/C in a slow stream of CO2, and a-tetralone is dehydrogenated to naphthalene by boiling (1 hour, with internal temperature of 235°) in the presence of Pd/C and a slow stream of CO in 75% yield. 

The oxidation of tetralin leads to the hydroperoxide, which can be split into 1-tetralone and 1-tetralol. Dehydrogenation of tetralone and tetralol takes place in two stages, to avoid the possible dehydration of tetralol on the platinum catalyst. In the first stage, tetralol is dehydrogenated to tetralone in the gas phase in the presence of hydrogen at 200 to 325 °C and nickel or copper catalysts in the second stage, dehydrogenation on the platinum catalyst at 350 to 400 °C produces 1-naphthol. 

The Haworth reaction is a classical method for the synthesis of tetralone, beginning with benzene and succinic anhydride. The three-step protocol involves a Friedel-Crafts acylation, followed by reduction of the arylketone, and an intramolecular Friedel-Crafts acylation. The tetralone analog may be further reduced and dehydrogenated to form new aromatic species, in what is known as the Haworth phenanthrene synthesis. 

The Haworth phenanthrene synthesis has been extensively used in the synthesis of derivatives of chrysene,an environmental pollutant which exhibits tumorigenic and mutagenic properties. For example Harvey and coworkers treated 61 with succinic anhydride under Friedel-Crafts conditions to produce 62. Reduction of the ketoacid under Wolff-Kishner conditions is followed by esterification to yield 63. Dehydrogenation of 63 is followed by saponification to yield carboxylic acid 64. Intramolecular Friedel-Crafts acylation produces tetralone derivative 65, which undergoes carbonyl reduction and dehydrogenation to produce 66. 

The Haworth phenanthrene synthesis was also employed for the preparation of naphthalene intermediates toward the synthesis of novel HMG-CoA reductase inhibitors/ The usual Haworth procedure was followed to secure tetralone 67. Hydride reduction of the carbonyl produced 68, which on dehydration to 69, was subsequently dehydrogenated with DDQ to provide naphthalene 70. A related procedure was used in the same work to replace the C-7 methyl with a chlorine atom. 

Note a-Naphthol is available by oxygenation of tetraline (tetrahydronaphthalene) to 1-tetralone followed by dehydrogenation (aromatization). The technological process is catalyzed by zeolites and oxygenation completed by oxygen. Intermediary 1-tetralone can be isolated or dehydrogenated to 1-naphthol by the same catalytic system. 

Two methods of synthesis of the acid (5) from 6-methoxy-l-tetralone (8), formed in two stages from nerolin (7) [139-142], have also been proposed. One of them [143, 144], like that just described above, is based on the introduction of the and 0 2 atoms by the Reformatskii reaction of the ketone (8). The ester formed (10) is converted into the bromide (11) and the 0 3 and 0 4 atoms are introduced by the condensation of the latter with sodiomalonic ester and decarboxylation. Dehydrogenation of the resulting acid (12) gives the acid (5). According to the other method for synthesizing this acid [140], the acids are introduced in one stage... 

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