Israel Agranat and Yu-Shan Shih The Hebrew University of Jerusalem Jerusalem, Israel
II
he Scope of the Haworth Synthesis
The Haworth synthesis provides a rational route to polynuclear aromatic svstems ( I ). It has convenientlv been illustrated hy the synthesis of phenanthrene (I) accordingto the following sequence of reactions (Fig. 1) (2): (a) Friedel-Crafts succinoylation of naphthalene (11) affording 3-(l-naphthoy1)propionic acid (111) and 3-(2-naphthoyl)propionic acid (IV), (b) Clemmensen reduction of e.g., (IV) to 4-(2-naphthyl)hutyric acid (V), (c) Intramolecular Friedel-Crafts acylation of (V) (e.g., in sulfuric acid) into 2,3-dihydro-4(1H)phenanthrone (VI), (d) Wolff-Kishner (or Clemmensen) reduction of (VI) to 1,2,3,4-tetrahydrophenanthrene(VII), and (e) Dehydrogenation of (VII) (e.g., by palladium on charcoal) to give phenanthrene (I). Alternatively, (111) could he trans-
XI1 Figure I.The Haworth synlhsis of phenanthrene and anthracene.
488 / Journal of Chemical Education
formed into (I) by an analogous sequence of reactions, through the intermediacy of 4-(l-naphthy1)hutyric acid (VIII), 2,3dihydro-l(4H)-phenanthrone (IX) and (VII). The crucial transformation in the sequence
is the cyclization reaction (c) which produces the phenanthrene carbon skeleton. In this reaction, the conjugate acid of (V) cyclizes into the reactive l-position (a-type) of the naphthalene nucleus rather than into the less reactive 3position (&type) to yield 3.4-dihydro-l(2H)-anthracenone (X). Modem texthwks (includingvery recent ones) frequently state that ring closure occurs only in the l-position of naphthalene and not in the 3-position. Thus it has widely been accepted that only angularly annelated polycyclic aromatic systems (e.g. phenanthrene) could he obtained through the Haworth synthesis. (A trivial exception is naphthalene.) These
X Figure 2. Pmposed mechanism f a the Haworth synlhesis.
statements have recently been challeneed in the lieht of the following realizations: (i) The incursion of reveriibility in Friedel-Crafts acvlations in polwhos~horicacid (PPA) (3). (2) The devrlopmenr of a general ryn;hesis of linearly annelated polycyclic aromatic ketones hv controlled Friedel-Crafts rearrangements of their angular isomers ( 4 ) . Indeed, application of the reversibility concept to the intramolecular acylation of (V) in PPA has revealed that cyclization could occur also in the 3-position, affording (X) (5). Moreover, the synthesis of (X) has also been accomplished hy the rearrangement of (VI) in PPA under thermodynamically controlled conditions (5).It appears that in PPA, the intramolecular acylation of (V) a t the a-position of the naphthalene nucleus is a reversible process, in which the conjugate acid of (VI) is the kinetically controlled product and the conjugate acid of (X) is the thermodvnamicallv controlled ~ r o d u c t . The wigin of this '~the~mudvnamir"differenee between the two ketones (VII and cX) (and between [heir conjugateacidsJ is inherent in the spatial relationship of the carb(,nyl group vis-&\.is the naphthalene nucleus. In the anaularlv annelated ketone (VI), the peri-hydrogen causes a tilting of
