Bernthsen

BERNTHSEN Acndine synthesis Acndine synthesis from diphenylamine and cartxixylic acids... 

Dandliker, G. and Bernthsen, H.A. U.S. Patent 416,055 November 26, 1889 assigned to Badische Anilin and Soda Fabrik, Germany... 

Fleischer1 prepared benzylaniline by heating aniline with benzyl chloride at i6o°. This reaction may be very violent and always leads to mixtures. Bernthsen and Trompetter 2 reduced thiobenzanilide with zinc and hydrochloric acid or sodium amalgam, while O. Fischer 3 reduced bcnzalaniline with sodium and alcohol, to benzylaniline. Knoevenagel4 obtained a 32 per cent yield of benzylaniline from benzyl alcohol and aniline in the presence of iodine. Ullmann5 describes the preparation of benzylaniline from benzyl chloride and excess of aniline at low temperatures. 

Bernthsen,1 whose brilliant work elucidated the constitution of the dye, suggested a technical process in which, at stage I, thiosulphuric acid is added its sulpho-group is eliminated as sulphuric add in the course of the process. 

A. Bernthsen und F. Bender. Notiz fiber einige Derivate des Styrols. Ber., 1S82, 15, 1982-1986. 

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). 

Many acridines and benzacridines have been synthesized by the Bernthsen reaction (l884LA(224)l) in which a diphenylamine is heated with a carboxylic acid and zinc chloride, with or without aluminum chloride. The reaction has been reviewed (73HC(9)141), and will be outlined here. The yields are not generally high one of the better examples is the synthesis of 2-chloro-9-methylacridine (312) (63BCJ1477). In the synthesis of the... 

The formation of 4-chloroquinolinium salts from iV-vinylanilines (308) and carbonyl chloride, mentioned earlier, is a reaction related to the Bernthsen synthesis. 

In 1874 Claus [5] reported that thiourea reacts with ethyl iodide or bromide to give compounds whose structures were first suggested to be pseudothioureas by Bernthsen and Klinger [6] (Eq. 3). In place of thiourea, symmetrical... 

Before the synthesis of the pseudoureas was published, Bernthsen and Klinger [6] reported a pseudothiourea synthesis involving the reaction of thioureas with alkyl halides. This reaction was briefly reviewed by Dains [16] and Stieglitz [49, 50], and it found many commercial applications [51-53]. The preparation of isothiouronium salts by the direct action of thiourea and halogen acids on alcohols (primary, secondary, and tertiary) was reported by Stevens [8] and further developed by Johnson and Sprague [54, 55] (Eq. 25). 

Juglone is most readily synthesized by Bernthsen s method. Although it no longer has any commercial value as dye. It is a fungicide and as such finds use in the treatment of skin diseases Its toxic properties have been made use of in catching fish. Juglone has been used lo detect very small amount of nickel salts since it gives a deep violet color wiih such salts. 

Anilino-553 and the three 3-tolylaminobenzo[6]thiophenes554 undergo the Bernthsen reaction when heated with an aliphatic carboxylic acid anhydride and zinc chloride 1o yield polycyclic compounds (e.g., 181 from 3-m-tolylaminobenzo[6]thiophene and acetic anhydride), They give analogous arsenic derivatives (e.g., 182 from 3-p-tolylaminobenzo[6]thiophene) when heated with arsenic trichloride in o-dichlorobenzene.553,554... 

A Bernthsen, A Textbook of Organic Chemistry, New edition, revised by J.J. Sudborough, 1922, Blackie, London. 

In the Bernthsen synthesis, diphenylamine 61 and carboxylic acids form 9-substituted acridines 62 (Scheme 31). 

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