Pschorr phenanthrene synthesis

Intramolecular arylations can also be carried out photochemically. Huisgen and Zahler (1963 a) prepared fluoren-9-one by irradiation of benzophenone-diazonium salts in dilute sulfuric acid. The classical Pschorr synthesis of phenanthrene-9-carb-... 

Pschorr Synthesis. In this synthesis of phenanthrene derivatives, one of the steps involves the union of two aryl nuclei through a diazotiza-tion reaction. By treatment of diazotized a-phenyl-o-aminocinnamic add with copper, 9-phenanthroic add is obtained.24... 

Intramolecular arylation is an important step in the Pschorr synthesis of phenanthrene from cis-o-aminostilbene. ... 

Pschorr synthesis. The Pschorr synthesis of phenanthrene derivatives is usually carried out with copper powder. Australian chemists1 report that a diazotized 2-phenyl-3-(2-aminophenyl)acrylic acid of type (1) undergoes practically instantaneous cyclization in the presence of sodium iodide (acetone is used as solvent). When copper powder is added the Pschorr method requires more than ten hours and the yield is 55%. 

The Pschorr reaction is a method of synthesis of phenanthrenes from diazotized Z-2-aminostilbenes. A traditional procedure involves heating with a copper catalyst. Improved yields are often observed, however, if the diazonium ion is treated with iodide ion. Suggest a mechanism for the iodide-catalyzed reaction. 

Pschorr s synthesis of phenanthrene (1893) in five steps with the essential dediazoniation and ring closure of 2-diazonio-a-phenylcinnamic acid giving, on addition of copper powder, phenanthrene-9-carboxylic acid, is today still the highest yielding one of all the reactions discussed in this section, Pschorr was able to get 93% yield, and today electrochemically induced Pschorr and related reactions141 give almost quantitative yields in several cases. 

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. 

Cohare and co-workers reported that aristolactam BU (22) was prepared, following Kupchen s method, by Perkin condensation of 6-bromo-3,4-di-methoxy phenyl acetic acid (119) and o-nitrobenzaldehyde (120) (Scheme 14). The 2-bromo-4,5-dimethoxy-2 -nitro-ds-stilbene-a-carboxylic acid (121) was obtained. The nitro group of 121 was reduced with ferrous sulfate and ammonium hydroxide, and the resulting 2-bromo-4,5-dimethoxy-2 -amino-cw-stilbene-a-carboxylic acid (122) without purification was submitted to the Pschorr phenanthrene synthesis to yield l-bromo-3,4-dimethoxyphen-anthrene-lO-carboxylic acid (123). The phenanthrylamine 124 was prepared from 123 via a Schmidt reaction, and, by treatment with n-butyllithium and CO2, 124, afforded 22 (42). 

Pschorr reaction. Synthesis of phenanthrene derivatives from diazotized a-aryl-omicron-amino-cinnamic acids by intramolecular arylation. 

Hofmann degradation of N-methylthebenine dimethyl ether methiodide or methomethylsulphate, which result from the complete methylation of thebenine, affords 3 4 8-trimethoxy-5-vinylphenan-threne [vn], the 4-methoxyl group of which is so readily hydrolysed that boiling with acetic acid or alcoholic hydrogen chloride results in formation of methebenol and bromination in formation of bromo-methebenol [8], 3 4 8-Trimethoxy-5-vinylphenanthrene can be reduced to 3 4 8-trimethoxy-5-ethylphenanthrene, identical with a specimen prepared from 2-nitroveratric aldehyde and 2-methoxy-5-ethylphenyl-acetic acid by the Pschorr phenanthrene synthesis [11]. 

For an excellent overview of Pschorr phenanthrene synthesis see D.F. DeTar, Organic Reactions, 9, (1957), 409. 

Structure. The structure of glaucine was arrived at by Gadamer (12) by a process of intuitive reasoning supplemented by a synthesis. Co-rytuberine dimethyl ether and glaucine were known to be isomeric, and if a relation to papaverine were admitted only two structures were available for the two alkaloids. Pschorr (13), utilizing his well-known phenanthrene synthesis, had attempted to convert papaverine into an aporphine (IV) via the nitro (II) and the amino (III) derivatives. When papaverine is nitrated it yields 6 -nitropapaverine (II), from which the methochloride... 

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. 

Methodology similar to Pschorr and Motherwell reactions, was employed in the synthesis of phenanthrene-type structures, where an intramolecular free-radical arylation was accomplished by the reaction of bromo-c/s-stilbene 428 with tri-n-butyl tin hydride, giving 429 in 85% yield [6], respectively. Scheme 4. 

Important work on alkaloids, particularly quinine, was done by Skraup (see p. 837) and his collaborator Wilhelm Konigs (Diilken, 22 April 1851-Munich, 15 December 1906), a pupil of Kekule and professor in the University of Munich. R. F. Pschorr, professor in the Technical High School, Char-lottenburg, worked on the synthesis of phenanthrene derivatives and their relation to morphine and other alkaloids. The important work on berberine and harmaline by W. H. Perkin jimr. and collaborators can only be mentioned. 

When Pschorr reported more than a century ago on the first intramolecular homolytic aromatic substitution [25], he showed that biaryls could be readily prepared by intramolecular homolytic aromatic substitution using reactive aryl radicals and arenes as radical acceptors. The aryl radicals were generated by treatment of arene-diazonium salts with copper(l) ions. Today, this reaction and related processes are referred to as Pschorr reactions. It was later found that radical biaryl synthesis could be conducted without copper salts by photochemical or thermal generation of the aryl radical from the corresponding diazonium salt [26], Moreover, the reduction of aryl diazonium salts offers another route to generate reactive aryl radicals. Hence, electrochemistry [27], titanium(lll) ions [28], Fe(II)-salts [29], tet-rathiafulvalene [30] and iodide [31] have each been used successfully for the reduction of diazonium salts to generate the corresponding aryl radicals [32]. As an example, the iodide-induced cycUzation of diazonium salt 6 to phenanthrene derivative 7 is presented in Scheme 13.3 [31]. For further information on the... 

Scheme 13.24. The demonstration of the location of oxygen substituents in thebaine (and hence morphine and codeine) and the presence of a phenanthrene (barring rearrangement) system. The degradative work is from Vongerichten, E. Dittmer, O. Chem. Ber., 1906,39,1718. The synthesis, using the sodium salt of the 4-methoxyphenylacetic acid reacting with the nitrobenzaldehyde derivative (in acetic acid for 3 days at 100°C) followed by reduction [rron(II) sulfate], diazotization (sodium nitrite in methanolic sulfuric acid), cychzation, and pyrolysis (loss of carbon dioxide) was effected by Pschorr, H. Liebigs Ann. Chem., 1912, 391,40.

Using this methodology in 1896, Pschorr first reported the synthesis of phenanthrenes from the corresponding (Z)-2-styiylbenzenediazonium salts promoted by Cu+ [10]. Later, in 1924, Gomberg and Bachmann showed that biaryls could be prepared by intermolecular HAS from aryldiazonium salts and benzene [11]. However, yields were generally low (<40%), and many side reactions of diazonium salts were observed. 

SCHEME 29.12 Synthesis of phenanthrene by photocatalytic Pschorr reaction. 

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