Tetralone ring closure

Tetrahydro-l-benzazepin-2-ones are formed from a-tetralone by Beckmann or related reactions (CHEC 5.16.4.1.1). Classical ring closures (of the Friedel-Crafts, Dieckmann, etc. types) can also be applied to benzazepine synthesis (74AHC(17)45). 

The formation of a six- in preference to a seven-membered, ring follows as a corollary from the above considerations. Experimental foundation, moreover, was afforded by examination of the ring closure of j8-benzyl-adipic acid (XVII), which was found to yield only the tetralone derivar tive XVIII.11... 

Treatment of 2-(l-naphthylaminomethylene)-l-tetralone (143) with formic acid provides 7,8-dihydro-3,4 9,10-dibenzophenanthri-dine (144),177 although the simpler 2-anilinomethylene-l-tetralone (145) does not give a phenanthridine derivative under similar conditions.30 177 The observation30 that ring closure of 145 with hot formic acid, followed by treatment with ammonia, gives 5,6,8,9-tetrahydro-dibenz[c7t]acridine has been confirmed, and is rationalized in terms of an intermediate xanthylium formate. The nitrogen atom in the final product comes from the ammonia used in the reaction.177... 

The reaction of 2-iodobenzoic acids derivatives (288) with tetralone enolate ions (284) gives the products 291 which, after acid treatment, afford the ring closure compounds 292 (60-75% yield) (equation 179)328. 

Ring closure of the diastereoisomeric mixture (61) gave the isomeric tetralones (62 and 63) in the ratio 4 1. By conventional means the cis isomer 62 was converted to the required 3,11/3-dimethylbenzomorphan (64), which exhibited codeine-like activity. Similar treatment of the trans substituted tetralone (63) gave only the naphthalene (65). 

A further technique has been described, which leads to the equilenin-like 15-aza-steroid (178), and it is summarized in Scheme 14. Condensation of the tetralone (172) with the bromo-ester (173) gives the diene (174). Aromatiza-tion of ring b is followed by cyclization and alkylation, thus affording the tricyclic ketone (176). Conversion of the cyano-group into the corresponding acid chloride (177) is then followed by ring closure, yielding the aza-steroid (178). " ... 

There seems to be some indication that a-substituted 7-arylbutyric acids can be cyclized by sulfuric acid in better yields than the unsubstituted acids. Thus, whereas 7-phenylbutyric acid has not been cyclized in yields exceeding 50% with sulfuric acid (Table III), the a-methyl and a-ethyl homologs have been converted to the tetralones in 98% and 86% yields respectively. Similarly a-methyl-7-l-naphthylbutyric acid was cyclized in 91% yield, althou in the case of the unsubstituted acid yields over 75% could not be obtained. This peculiarity may be explained by the fact that ring closure of acids containing a substituent in the a-position gives rise to ketones lacking the usual reactive methyl-... 

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. 

The stereoselective total synthesis of the delphinine degradation product (158) has been described. The key stages involved the conversion of the tetralone (152) into the aldehyde (153) and its ring-closure to (154). This product was then converted into the compound (155), which underwent cyclization to form the lactam (156) in the presence of potassium cyanide. On acid hydrolysis, this was converted into the lactam (157), which was in turn transformed into (158), the... 

Posner has devised a novel one-pot (but low yield) synthesis of ( )-9(ll)-dehydro-8-epiestrone methyl ether 210 by a coupled sequence of two Michael reactions and a Wittig reaction (tandem Michael-Michael ring closure) (Scheme 26), 6-Methoxy-l-tetralone 205 was converted, via trimethylsilyl enol ether... 

In one synthetic approach, the bicyclic isonitriles were cyclized with strong bases to the corresponding tricycUc compounds [42]. A synthesis of dihydro-lysergic acid starting from appropriately substituted 5-nitro-2-tetralones via a tricyclic isonitrile to the indole ring closure as the last step has been described [43]. 

Halogens have been widely used to direct electrophilic ring closures, such as in the following synthesis of indanones [68], tetralones [69, 70], and Stobbe-type [71, 72] condensations to give naphthalenes e.g. Fig. 1.27. 

Lactone opening A crucial operation in a synthesis of 12a-deoxytetracycline requires a mild alcoholysis of a lactone under conditions precluding closure of the B-ring, because intermediates with the linear tricarbocyclic array resist further cyclization. After successful lactone opening by treatment with Bu,SnOMe, the a-tetralone unit can be masked as a lactol silyl ether to permit a Dieckmann cyclization to form the A-ring. 

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