Naphthalenes Haworth synthesis

Synthesis of naphthalene from benzene Haworth synthesis... 

Fig. 5.34. Steps 1-3 of the five-step Haworth synthesis of substituted naphthalenes.

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-tetraione and reduction of the carbonyl group then gives 1,2,3,4-tetrahydronaphthalene (tetralin). Aromatization is achieved by dehydrogenation over a palladium catalyst. 

Although it is possible to synthesize anthracene in a number of ways using Friedel-Crafts methodology, the usual routes involve either an adaptation of the Haworth synthesis of naphthalene or a Dicls-Alder reaction using naphtho-l,4-quinone as the dienophile. 

There are two major routes to phenanthrene, both of which can be used to prepare substituted derivatives. In the Haworth synthesis (Scheme 12.11), reaction of naphthalene with succinic anhydride yields an oxobut-anoic acid which is reduced under Clemmensen conditions to the butanoic acid. Cyclization in sulfuric acid and reduction of the resulting ketone is followed by dehydrogenation over palladium-on-carbon to phenanthrene. Alkyl or aryl derivatives can be obtained by treatment of the intermediate ketone with a Grignard reagent prior to dehydration and oxidation. 

As an example, let us look at just one method used to make certain naphthalene derivatives the Haworth synthesis (developed by R. D. Haworth at the University of Durham, England). Figure 30.2 (p. 987) shows the basic scheme, which would yield naphthalene itself (not, of course, actually prepared in this way). 

A further example is given below illustrating the use of a dibasic anhydride (succinic anhydride) the succinoylation reaction is a valuable one since it leads to aroyl carboxylic acids and ultimately to polynuclear hydrocarbons. This general scheme of synthesis of substituted hydrocarbons through the use of succinic anhydride is sometimes called the Haworth reaction. Thus a-tetralone (see below) may be reduced by the Clemmensen method to tetralin (tetrahydronaphthalene) and the latter converted into naphthalene either catal3d.ically or by means of sulphur or selenium (compare Section, VI,33). 

The mechanism of Wolff-Kishner reductions is exemplified in Figure 17.67 with the second step A — E of the Haworth naphthalene synthesis (steps 1 and 3 of this synthesis Fig-... 

Starting from naphthalene instead of benzene, the Haworth succinic aithyxiFide synthesis (Sec. 30.14) provides an excellent route to substituted phananthrenes. 

Apply the Haworth method to the synthesis of the foRowing, starting from naphthalene or a monosubstituted naphtfaalenev... 

Benzanthracene, Benzlajanthracene 2,3-benzphenanthrene tetraphene benzanthrene naphthanthra-cene. C,HI2 mol wt 228.28. C 94.70%, H 5.30%. Occurs in coal tan Cook el at. J. Chcm. Soc. 1933, 395. Synthesis from naphthalene and phthalic anhydride Elbs, Her. 19, 2209 (1886). From o-to uy] naphthalene Fieser, Dietz, Ber. 62, 1827 (1929). From phenanthrene and succinic anhydride Haworth, Mavin, J. Chcm. Soc. 1933, 1012. Absorption spectrum Capper, Marsh, J. Chem. Soc. 1926, 726 Clar. Ber. 65, 507 (1932) Mayneord, Roe, Proc. Roy. Soc. London A152, 299 (1935). Review E. Clar. Polycyclic Hydrocarbons (Academic Press, New York, 1964) 2 vols. 

Although the modem Haworth reaction is more commonly used to form tetralone analogs, the reaction sequence first targeted the synthesis of phenanthrene and its derivatives. The original protocol used by Robert Downs Haworth in 1932 involved the reaction of naphthalene (1) with succinic anhydride (2) and aluminum chloride to form nearly equal quantities of naphthoylpropionic acids 3 and 4. 

The tetralone derivatives produced by the Haworth reaction are important synthetic intermediates. However, in Haworth s original work, his efforts were directed toward the synthesis of phenanthrene fi-om naphthalene. Thus the synthesis of tetralone derivative 12 by the standard Haworth conditions is followed by a Clemmensen " or Wolff-Kishner reduction of the ketone... 

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. 

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