SYNTHESIS Pschorr cyclization

This interpretation of the Hofmann degradation has been strengthened by the conversion of anhydrolycorinium chloride (XL) via XXXIX to ( )-anhydrolycorine methiodide (XXXIVc). Anhydrolycorinium chloride, originally called isolycorine hydrochloride by Kondo and Tomimura (107), is formed by the action of either phosphorus oxychloride or pentachloride on lycorine (108). The assigned structures have been verified by synthesis. Pschorr cyclization of l-(2-amino-4,6-methylenedioxybenzoyl)-indoline (XXXVII) gave the lactam... 

The Reissert method15—conversion of an isoquinoline to a 2-benzoyl-1,2-dihydroisoquinaldonitrile (Reissert compound), alkylation, and hydrolysis—has enjoyed wide success in the synthesis of benzyliso-quinoline and related alkaloids.16,17 In particular, aporphines are prepared conveniently by converting isoquinolines to I-(o-nitrobcnzyl)-isoquinolines via a Reissert sequence, followed by A7-alkylation, reduction, and Pschorr cyclization.17... 

Reissert alkylation and Pschorr cyclization have frequently been utilized for the synthesis of oxoaporphine alkaloids by Cava and co-workers. Their synthetic... 

Pschorr cyclization of diazotized A-mesyl-o-aminodiphenylamine yields A-mesyl-5,7-dihydro-6H-dibenz[c,e]azepine (73AJC1307). Diazonium compounds also feature in the preparation of 1 lH-dibenz[6,e]azepines via nitrilium ions (Scheme 21) (72CB1634), and in the only synthesis reported so far of a tribenz[6,rf,/]azepine (10 R=Ph) (72CB880). 

The synthesis of three l,2,10,ll-tetrasubstituted./V-(n-propyl)noraporphines, using either the Bischler-Napieralski-Pschorr sequence or a Reissert alkylation-Pschorr cyclization, has been achieved.29 Patents have been taken out on the morphine-apomorphine rearrangement that is induced by phosphoric acid and which leads to N- alkylated norapomorphines.30 Other patents concern the vanadium-trichloride-induced cyclization of tetrahydrobenzylisoquinolines that are hydroxylated at C-7, to furnish a series of 1-hydroxylated aporphines such as thaliphorphine. 31,32... 

A synthesis of homomoschatoline (1,2,3-trimethoxyoxoaporphine) via a Reissert intermediate and Pschorr cyclization has been described/ and a photolytic synthesis of atheroline (l,2,10-trimethoxy-9-hydroxyoxoaporphine) is now available/ The u.v. spectra of oxoaporphines are strongly dependent on the solvent used. ... 

The use of 2-nitrobenzyl halides in the Reissert alkylation, followed eventually by the Pschorr cyclization, has provided an attractive route to various aporphines (31). Thus this procedure had led to the synthesis of apomor-phine, ° apomorphine derivatives, atheroline, imenine, N-methyl-ovigerine, oconovine, 8-hydroxyaporphines, 10-hydroxyaporphines, ... 

The synthesis of racemic l,2-methylenedioxy-3-methoxyaporphine via a Pschorr cyclization and its oxidation to atherospermidine (3) by chromium trioxide in pyridine has been achieved (28). 

This suggestion received support through a total synthesis of cassameridine via Pschorr cyclization of the amino ketone 8c 42). A direct comparison of the two materials was not possible, but the UV spectra of the samples were found to be very similar. Cassameridine has also been efficiently synthesized by peracetic acid oxidation of dehydroneo-litsine (8d) and by iodine oxidation of norneolitsine (8e) 41a). 

Further studies of the synthesis of the aporphine alkaloids were carried out to find simpler procedures and to increase the yields. The most frequently applied methods are the Bischler-Napieralski reaction (91, 408, 408a, 449, 450), the Pschorr cyclization (451, 452), and the photocy-clization of various benzylisoquinoline precursors (416a, 453,454) (Scheme 10). 

R = H) in 20% yield. Compound (111 R = OMe, R == H) has also been synthesized by a conventional Pschorr cyclization route.The photochemical oxidation of glaucine to 7-oxoglaucine has been reported. Photochemical synthesis of the unusual aporphine alkaloid thalphenine (113 N-Mel) has been achieved. Irradiation of (114) under basic conditions gave directly (113), presumably via the intermediate quinone methide (115), which results from the initially formed aporphine precursor by elimination of the elements of methanol. Quaternization of (113) provided ( )-thalphenine (113 A/-Mel), whose Hofmann elimination gave the alkaloid thaliglucine (93 R = H2). 

The intramolecular coupling reaction between an aryldiazonium salt (III) with an arene subunit to form five- or six-membered ring by the influence of copper or an acid, is called the Pschorr cyclization reaction [85]. In historical examples the Pschorr cyclization was used in the synthesis of phenanthrene and its derivatives. For example, c -stilbene derivative 49 is diazotized to give 50, and subsequently treated with the activated copper to obtain phenanthrene (51) in 34% yield [86], Scheme 21. 

The Pschorr cyclization reaction was used in the synthesis of a wide variety of phenanthrene and related type of structures [88,89,91-95]. An interesting example is diazotation of 54 to produce 55, which by intramolecular cyclization gave 56 in 46% yield [92], Scheme 23. 

Neumeyer JL, Oh KH, Weinhardt KK, Neustadt BR (1969) The chemistry of aporphines. IV. Synthesis of aporphines via Reissert alkylation, photochemical cyclization OR the Pschorr cyclization route. J Org Chem 34 3786-3788... 

The Pschorr reaction, originally applied to the synthesis of phen-anthrene and its derivatives,has been adapted to the formation of new heterocyclic systems.In its original form, it consisted of treating a diazonium salt with copper powder in acid solution in this way, rans-o-amino-a-phenylcinnamic acid was converted into phen-anthrene-9-carboxylic acid, Eq. (20). Variants of the reaction include cyclizations such as that in Eq. (21). The reaction may be horaolytic... 

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