Cyclization Pschorr

Pschorr, R. Ber. Dtsch. Chem. Ges. 1896, 29, 496. Robert Pschorr (1868—1930), born in Munich, Germany, studied under von Baeyer, Bamberger, Knorr, and Fischer. He became an assistant professor in 1899 at Berlin where he discovered the phenanthrene synthesis. During WWl, Pschorr served as a major in the German Army. 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 209, Springer-Verlag Berlin Heidelberg 2009 

Name Reactions A Collection ofDetailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 224, Springer International Publishing Switzerland 2014 

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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... 

This also may be looked upon as a substituent reaction (see Chapter 2.06) but a few examples are given here. A suitably substituted pyridine will undergo Pschorr cyclization to give 2- and 4-azafluorene and two other products (equation 181) (65CJC940). With a 2-substituted pyridine (287), cyclization on to the pyridine nitrogen is heavily favoured (equation 182) (54JCS4263). Decomposition of 3-(o-azidophenyl)pyridine results in a nitrene... 

The Pschorr cyclization of the diazonium fluoroborate from A-methylanthranilamide can be used to make iV-methylphenanthridinone (67JCS(C)1513). 

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 bases (142 R = H) and (142 R = Me) have been synthesized by Pschorr cyclizations of the appropriate benzylisoquinolines.173 Oxidative cyclization of 7V-(carbethoxy)nor-reticuline with titanium trifluoroacetate gives N-(carbethoxy)norsalutaridine, and the same process with the seco-reticuline... 

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... 

As shown in other sections of this chapter, overall attention has shifted from diazonium salts as aryl radical sources to bromo- or iodobenzenes. One of the few recent attempts to improve the classical Pschorr cyclization using diazonium ions as starting materials led to the discovery of new catalysts [119]. Results from a first samarium-mediated Pschorr type show the variety of products that can be expected from intramolecular biaryl syntheses under reductive conditions (Scheme 22). Depending on the substitution pattern of the target aromatic core and the reaction conditions, either the spirocycle 60, the biphenyl 61, or the dearomatized biphenyl 62 were formed as major product from 63 [120]. 

In a modification of a known sequence, base-catalysed condensation of hydrastininium iodide (18) with 6-methoxy-2-nitrotoluene (19) provided (20) and (21). Catalytic hydrogenation of (20), followed by Pschorr cyclization, afforded stephanine (22).44... 

The same conditions are useful in the intramolecular version of the reaction (Pschorr cyclization). 

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, ... 

Napieralski cyclization of (79) in the presence of the very effective reagent polyphosphate ester, to yield the dihydroisoquinoline derivative (80). Two successive oxidation stages led to the fully aromatic system (81) which, upon reduction and Pschorr cyclization, gave cassameridine (82).112... 

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 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). 

Catalytic hydrogenation of 7a in the presence of Raney nickel followed by Pschorr cyclization, gave mainly the desired oxoaporphine 7b. Debenzylation was achieved in hydrochloric acid and tetrahydro-furan to afford atheroline in good yield. 

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). 

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