Skraup procedure

Thiazolo[5,4-/i]quinoline 22 was prepared 2 years later starting from 4-ami-nobenzothiazole, also by the Skraup procedure. The 4-aminobenzothiazole was prepared in six steps from 2-nitroaniline (40HCA328) (Scheme 11). 

The violence of the original Skraup procedure may be eliminated by the addition of 100 cc. of 80 per cent acetic acid for every 60 cc. of 95 per cent sulfuric acid. Cohn and Gus-tavson, J. Am. Chem. Soc. So, 2709 (1928). 

The Skraup procedure is applicable to quinoline derivatives substituted in the benzene ring, providing these substituents are not strongly electron withdrawing. 

Note This synthesis involves cyclocondensation of the 2-pyridinamine with a 1,5-dicarbonyl synthon or equivalent. Although the classical Skraup procedures may be used,172 348 755 yields are usually poor. 

The parent 1,8-naphthyridine was first made by catalytic dechlorination of 2,4-dichloro-l,8-naphthyridine (no details) 30,33 it is probably best made by a Skraup procedure (33%)250 or by a modified Friedlander procedure (80%).1441 Other routes have been mentioned in Chapter 22. 

Cellobiose was prepared first by Skraup and Konig by the saponification of the octaacetate with alcoholic potassium hydroxide, and the method was improved by Pringsheim and Merkatz.3 Aqueous barium hydroxide also has been employed for the purpose, and methyl alcoholic ammonia has been used extensively for the hydrolysis of carbohydrate acetates. The method of catalytic hydrolysis with a small quantity of sodium methylate was introduced by Zemplen,i who considered the action to be due to the addition of the reagent to the ester-carbonyl groups of the sugar acetate and the decomposition of the addition compound by reaction with alcohol. The present procedure, reported by Zemplen, Gerecs, and Hadacsy, is a considerable improvement over the original method (see Note 2). 

Quinolines 3 can be obtained from reaction of orr/zo-aminobenzaldehydes or o-aminoarylketones 1 with a-methylene carbonyl compounds.Various modified procedures are known a related reaction is the Skraup quinoline synthesis. 

Bismuth triflate catalyzes the synthesis of 1,2-dihydroquinolines in an improved version of Skraup s procedure [74]. Accordingly, treatment of aniline with... 

The importance of 1,10-phenanthroline and substituted 1,10-phenanthrolines as metal complexing agents and their use in analytical applications has provided the impetus for an extensive study of procedures for their synthesis.182 The original synthesis of 1,10-phenanthroline by a double Skraup reaction on o-phenylenediamine using glycerol and sulfuric acid in the presence of an oxidizing agent continues to attract attention, and various improvements in reaction... 

An important use of the traditional Skraup synthesis is to make 6-methoxy-8-nitroquinoline from an aromatic amine with only one free ortho position, glycerol, the usual concentrated sulfuric acid, and the oxidant arsenic pentoxide. Though the reported procedure uses 588 grams of As2Os, which might disconcert many chemists, it works well and the product can be turned into other quinolines by reduction of the nitro group, diazotization, and nucleophilic substitution (Chapter 23). 

The classical method of quinoline synthesis involves Skraup s procedure. " However, it requires a large amount of H2SO4 at elevated temperature and the reaction often becomes violent. 

The use of this reagent was first described in 1881 by Z.H. Skraup, but the pharmacopoeia uses a special version of the procedure where selectivity is enhanced by extracting the precipitate into chloroform with the aid of butylamine. 

Skraup synthesis. It has now been reported that a convenient and cost effective preparative method results by using silver-loaded titania as the photocatalyst. In a similar way, n-nitroanilines are reduced to 1,2-phenylendiamines on Pt-loaded Xi02. Under these conditions condensation and dehydrogenation ensue leading to 2-arylbenzimidazoles in a convenient one-pot procedure that combines catalysis and photocatalysis (see Scheme 4). °... 

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