ThePschorr Synthesis and Related Diazonium Ring Closure Reactions

Abstract

In the middle 1890s, three groups of chemists independently discovered a new cyclization reaction of certain appropriately constituted diazonium salts. Fischer and Schmidt reported that an aqueous solution of 2‐benzylbenzenediazonium chloride furnished fluorene on heating. Graebe and Ullman reported that 2‐benzoylbenzenediazonium chloride yielded fluorenone and Staedel reported a somewhat similar result from the action of nitrous acid on 2,2'‐diaminbenozpehnone, a reaction that produced a little 1‐hydroxyfluorenone. Two years later, Robert Pschorr applied the ring closure reaction to the diazonium salt derived from trans‐2‐amino‐alpha‐phenylcinnamic acid to obtain phenanthrene‐9‐carboxylic acid. The principal utility of these cyclizations reactions has been the synthesis of substituted ring structures in which the positions of the substituents are known.

A case of chain propagation: α-aminoalkyl radicals as initiators for aryl radical chemistry

“…Aer identifying optimal reaction conditions, we explored the scope of the transformation by evaluating different aryl halides (Scheme 4A). Aryl iodides substituted with electron withdrawing groups at the para-position reacted in good to high yields (3,(7)(8)(9)(10)(11). More challenging electron-neutral substrates as well as the ones equipped with electron-donating groups, which are elusive in some redox-based approaches, reacted well delivering the desired 2-aryl-pyrroles in good yields (11, 13 and 5).…”

“…20 We have recently demonstrated that generating a-aminoalkyl radicals from alkylamines (A / B) under photoredox catalysis represents an effective gateway to access alkyl and aryl radicals from the corresponding halides (Scheme 1B). 21 In this reactivity, the highly nucleophilic a-aminoalkyl radical B homolytically activates the sp 3 or sp 2 C-X bond by XAT (B + C / E) through a polarised transition state (D) stabilised by extensive charge-transfer character.…”

Mild and Regioselective Pd(OAc)2-Catalyzed C–H Arylation of Tryptophans by [ArN2]X, Promoted by Tosic Acid

“…[ArN 2 ]BF 4 salts share similarities with [Ar 1 IAr 2 ]X, in terms of both their structure and reactivity. 12 As oxidative addition of [ArN 2 ]BF 4 to Pd 0 is rapid, 13 , 14 we anticipated development of a mild and selective process, in the absence of an exogenous base. In this context, a mild methodology for the arylation of mainly indole derivatives was reported by Noel et al, employing aryldiazonium salts and catalytic Pd(OAc) 2 .…”

Synthesis of Tricyclic Tetrazoles by Cascade Diazotization/Intramolecular Radical C–H Heteroarylation of Arenes

“…In addition, the synthesis of 5,6-dihydrotetrazolo­[5,1- a ]­isoquinoline, another attractive scaffold with potential bioactivity, has rarely been known (Figure b), even though the 3,4-dihydroisoquinoline moiety that this compound contains has been found in molecules that display diverse biological properties, including anti-inflammatory and anticancer activities . Interestingly, however, the direct addition of heteroaryl radicals generated from 1-substituted tetrazole-5-diazonium salts to aromatic compounds has never been used to synthesize a variety of tricyclic tetrazoles, , although this is likely to be an effective route for the synthesis of these compounds. To our knowledge, the only known example of the preparation of a 1-substituted 5-aryltetrazole derivative by heteroaryl radical addition to an aromatic compound is the synthesis of 1,5-diphenyltetrazole using 5-nitrosoamino-1-phenyltetrazole as the heteroaryl radical source in the presence of benzene as both the coupling partner and solvent under reflux, which was reported by Butler and Scott et al in 1973 (Scheme a) .…”

“…This one-pot cascade reaction involves (1) the diazotization of the 1-substituted 5-aminotetrazole substrate using sodium nitrite and acetic acid at room temperature to afford the diazonium salt intermediate and (2) the subsequent intramolecular C–H heteroarylation of the arene in the intermediate at the same temperature to provide the desired tricyclic tetrazole product. In particular, the radical C–H heteroarylation of the intermediate proceeds without the need for heat, a catalyst, irradiation, or electrolysis. ,, Here, the cascade diazotization/intramolecular radical C–H heteroarylation of 1-benzyloxy-5-aminotetrazoles and 1-phenethyl-5-aminotetrazoles as substrates using sodium nitrite and acetic acid under mild reaction conditions is reported. The reaction efficiently provided 6 H -benzo­[ d ]­tetrazolo­[1,5- b ]­[1,2]­oxazines and 5,6-dihydrotetrazolo­[5,1- a ]­isoquinolines as the corresponding tricyclic tetrazole products in good yields.…”