Acridines, synthesis

Benzo[c]naphtho[2,3-/i]acridines synthesis, 2, 477 Benzo[a]naphtho[2,3 -yjacridines synthesis, 2, 477 Benzo[c]naphtho[2,3 -y Jacridines synthesis, 2, 477... 

ULLMANN - FEOVAOJAN Acridine synthesis Synthesis ot polynuciear pyridines from anilines, phenols and formaldehyde... 

Of greater versatility is an extension of Albert and Royer s acridine synthesis. The first successful use of this in the quinazoline series was for the removal of the chlorine atom in 2-chloro-4-phenylquin-azoline, although it had been used previously to prepare 8-nitro-6-methoxyquinazoline in very poor yield. The 4-chloroquinazoline is converted to its 4-(A -toluene-p-sulfonylhydrazino) quinazoline hydrochloride derivative which is decomposed with alkali in aqueous ethylene glycol at lOO C (Scheme 13). The yields are high (60-70%) when R is Me, Cl, OMe but low when R is NO2, and in the latter case it is preferable to use dilute sodium carbonate as the base. This reaction is unsatisfactory if the unsubstituted pyrimidine ring is unstable towards alkali, as in 1,3,8-triazanaphthalene where the pyrimi-... 

Ring closure y to a heteroatom is also a rather uncommon [5 + 1] procedure although there are some important exceptions. The most widely investigated is the Bernthsen acridine synthesis in which a diarylamine is condensed with a carboxylic acid in the presence of a Lewis acid (equation 73). More recently, it has been shown that acylanilines react with the Vilsmeier-Haack reagent to give quinolines in good yield (e.g. equation 74) and the mechanism of the reaction has been elucidated. A final example of [5 +1] ring closure y to a heteroatom which is of occasional use is the pyrazine synthesis outlined in equation (75). 

Diarylamines will also usually require strong acylating agents to undergo acylation. If Lewis acids such as ZnCl2 are used as catalysts the formation of an acridine can compete with N-acylation (Bemthsen acridine synthesis last reaction, Scheme 7.10). 

BERNTHSEN Acridine Synthesis Acridine synthesis from diphenylamine and carboxylic acids (see 1st edition). 

ULLMANN FEDVADJAN Acridine synthesis 394 ULLMANN - GOLDBERG Aromatic substitutions 395... 

BERNTHSEN Acridine synthesis Acridine synthesis from diphenylamme and carboxyfic acids... 

Acridines are an important structural feature of many natural products and medicinally important compounds. They can be produced in a straightforward manner by a Friedel-Crafts reaction, the Bernthsen acridine synthesis, 1 9 which couples diaryl amines (such as diphenylamine) with a carboxylic acid (such as benzoic acid) in the presence of a Lewis acid (zinc chloride, ZnCl2, is a typical reagent). Heating to 260°C (10 h) gave a 48% yield of acridine 317.1 9 ... 

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