The Pschorr cyclization

Pschorr cyclization reactions have been performed under the following conditions [88-97]  

The only by-product is the 2-iodo-a-arylcinnamic acid as a product of the reaction of the parent diazonium ion with the iodide. This can be also converted to 53 by photoarylation, see Chapter 7. 

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

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, ... 

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). 

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. 

Nuciferine (1,2-dimethoxyaporphine) has been prepared in good yield by a modification of the Pschorr cyclization step in which freshly prepared copper powder was employed as the catalyst. The intermediate iV-benzylnornuciferine was thus obtained in 60% yield. This represents one of the highest yields for a classical Pschorr cyclization reported to date. ... 

To 2.2. Radical Substitution] The phenylation of pyridine by radicals from the decomposition of 1-phenylazopyridinium tetrafluoborate has been describedi2606 and a full description of the Pschorr cyclization of diazotized 3-(2-aminobenzoyl) pyridine, already mentioned, has been publishedi262 ... 

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... 

Another example of the analogy between pyrazole and chlorine is provided by the alkaline cleavage of l-(2,4-dinitrophenyl)pyrazoles. As occurs with l-chloro-2,4-dinitrobenzene, the phenyl substituent bond is broken with concomitant formation of 2,4-dinitrophenol and chlorine or pyrazole anions, respectively (66AHC(6)347). Heterocyclization of iV-arylpyrazoles involving a nitrene has already been discussed (Section 4.04.2.1.8(i)). Another example, related to the Pschorr reaction, is the photochemical cyclization of (515) to (516) (80CJC1880). An unusual transfer of chlorine to the side-chain of a pyrazole derivative was observed when the amine (517 X = H, Y = NH2) was diazotized in hydrochloric acid and subsequently treated with copper powder (72TL3637). The product (517 X = Cl, Y = H) was isolated. 

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... 

Methods for intemuclear cyclization other than the Pschorr reaction have been used very little. Hey and Osbond prepared 7,8-di-... 

The decomposition of 2-(2-phenylphenylsulfanyl)benzenesulfonyl chloride (5) at elevated temperatures leads to the formation of tribenzo[6,c/,/]thiepin(6) in 24% yield by an intramolecular cyclization pathway. Mechanistically, this thermolysis is comparable to the Pschorr reaction (cf. Houben-Weyl, Vol. 5/2b, p 420 Vol. 10/3, p 189) however, copper(I) chloride is now preferred as a catalyst, without any solvent.4 In the thermolysis of 5, 4-phenyldibenzothiophene (7) is formed as a byproduct in 14% yield. Octachloronaphthalene can also be employed as a catalyst however, the yield of 6 is somewhat lower (19%).4... 

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... 

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). 

Although the bimolecular additions of aryl radicals to aromatic rings are not useful due to a lack of selectivity, the corresponding cyclizations are useful for constructing biaryl bonds. Equation (5) provides a generalized example of the Pschorr reaction.172 This cyclization of a diazonium salt is one of the classical methods for biaryl bond formation, and there are a variety of related reactions.138... 

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... 

Studies on the mechanism of the Pschorr reaction have led to a number of interesting cyclizations onto a pyridine nucleus. Hey and Osbond441 were the first to carry out such a reaction 7,8-dihydro-benzo[/]quinoline (211) was obtained in 41 % yield from the N-nitroso-acetanilide (210). The diazonium salt of the amine 212 also underwent cyclization in spite of the presence of a second deactivating... 

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]. 

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

In the Pschorr synthesis (Scheme 12.12), a Perkin reaction (see Chapter 6) between 2-nitrobenzaldehyde and sodium phenylacetate in the presence of acetic anhydride yields 3-(2-nitrophenyl)-2-phenyl-propenoic acid. Reduction of the nitro group and deamination of the resulting amine via its diazonium salt (see Chapter 8) is accompanied by cyclization. Thermal decarboxylation completes the sequence. 

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