Acidic ring closure

Acidic ring closure resembles the Du Pont process in that the central benzene ring of the quinacridone structure is synthesized totally. The process bears resemblance to the Liebermann method [2, see also 1.3]. Condensation of succinylosuc-cinic ester with two equivalents of arylamine affords 2,5-diarylamino-3,6-dihy-droterephthalic diester. Subsequent oxidation with suitable agents yields 2,5-di-arylaminoterephthalic diester 57. Hydrolysis and cyclization in polyphosphoric acid or other acidic condensation agents produces crude quinacridone [10]. This product already consists of very small particles. 

Performing the last step (thermal aftertreatment) in an appropriate solvent provides a simple and convenient method of producing the particular target crystal modification. 

The (3-crystal modification is prepared by pretreating the crude quinacridone product with alkali base before finishing with the solvent. Immediate solvent treatment, on the other hand, produces the 7-modification of the quinacridone pigment. 

Among syntheses which start from preformed aromatic systems, the Sandoz process in particular has stimulated interest. It is the only route which allows the manufacture of asymmetrically substituted quinacridones. A typical synthesis follows. 

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Anthra[l,9]pyrazol-6(2//)-one (735) dyes have also been described in the literature (B-70MI40403). TTiesc compounds result by acid ring closure of 1-anthraquinonyl hydrazine or its V-sulfonic acid. 

Fischer s original method for conversion of the nitrile into an aldehyde involved hydrolysis to a carboxylic acid, ring closure to a cyclic ester (lactone), and subsequent reduction. A modern improvement is to reduce the nitrile over a palladium catalyst, yielding an imine intermediate that is hydrolyzed to an aldehyde. Note that the cyanohydrin is formed as a mixture of stereoisomers at the new chirality center, so two new aldoses, differing only in their stereochemistry at C2, Tesult from Kiliani-Fischer synthesis. Chain extension of D-arabinose, for example, yields a mixture of D-glucose and o-mannose. 

In Table 23, [l,2,4]triazolo[4,3-tf]pyrimidine derivatives that have been synthesized either by acidic ring closure of 2-hydrazinopyrimidine (method A) or by oxidation of a 2-pyrimidylhydrazone (method B) are compiled. 

The BASF route started from hydroquinone, which was converted to 2,5-dihydroterephthalic acid by a Kolbe-Schmitt reaction. One mole of this acid was treated with two moles of an arylamine, both components being in the form of a suspension in aqueous methanol. This was added to a small amount of a solution of vanadium(III) chloride and sodium chlorate. Gentle heating gave a 95% yield of 2,5-bis(arylamino)benzo-l,4-quinone-3,6-dicarboxylic acid. Ring closure to the trans-quinacridonequinone took place in the presence of concentrated sulphuric acid at 60-80 °C. This was then reduced to the required crude pigment by zinc or aluminium powder in caustic soda under pressure,in an aluminium chloride/urea melt or by the use of a sulphuric acid/polyphosphoric acid mixture. 

A number of substituted derivatives of 305 (cis, n = 1, 2 trans, n = 2), 306 cis or trans), 307, and 308 diendo and diexo) (R = Me, Et, Ph, substituted aryl) were prepared from the corresponding amino acids with isothiocyanate and acidic ring closure of the resulting thiocarbamide... 

Most indoles are synthesized by the Fischer indolization reaction. Here a phenylhydrazine is first reacted with an aldehyde, or ketone, carrying an a-methylene group (not acetaldehyde). The corresponding hydrazone is then treated with an acid, often hydrochloric acid. Ring closure occurs, through a [3,3]-sigmatropic change, and ammonia (as the ammonium cation) is lost (Scheme 7.14). 

The fully aromatic diquaternary system 81 is prepared by acid ring closure of the salt (79) obtained by quaternization of 1,10-phen-anthroline with bromoacetaldehyde followed by dehydration of the resulting hydroxy diquaternary salt (80) with thionyl chloride.310,311 The salt 81 is unstable in aqueous solution above a pH of about 5.0. In the pH range 3.3-5.0 it is reduced by a one-electron transfer to the corresponding radical cation at a potential (E0) of —0.12 volt.311 Its reduction in dimethylformamide solution has also been studied.15,307 Substituted derivatives of 81 have been prepared.312... 

Keywords 2-aminobenzamide, o-phenylenediamine, benzoic acid, ring closure, melt reaction, benzimidazole, quinazolinone... 

Stannic Chloride pn the Free Acid. Ring closure by heating the free acid with stannic chloride at 100-120° has been shown to be successful on several types of acids.85 47> 8 88 80, 189 819 These and some other acids which have been cyclized by this method may be found in Table XI. In four instances (items 3, 7, 14, 17) stannic chloride treatment gave better results than sulfuric acid. Eleven of the acids in Table XI (items 3, 5, 8, 9, 10,12, 13, 14, 16, 17, 18) have been cyclized also by the Friedel-Crafts method on the acid chloride. With seven acids (3, 6, 8, 9, 12, 14, 17) the yields were better, while with four (5, 10, 16, 18) they were lower, than with stannic chloride. Except for one (18) of these latter acids, however, there seems to be some question as to whether the optimum conditions for the Friedel-Crafts reaction were employed. Of the acids (4, 6,12) which have since been cyclized with hydrogen fluoride, considerable improvement in yields was realized. 

There are two main synthetic routes to naphthalene the Haworth synthesis and a Diels-Alder approach. In the Haworth synthesis (Scheme 12.1), benzene is reacted under Friedel-Crafts conditions with succinic anhydride (butanedioic anhydride) to produce 4-oxo-4-phenylbutanoic acid, which is reduced with either amalgamated zinc and HCl (the Clemmensen reduction) or hydrazine, ethane-1,2-diol and potassium hydroxide (the Wolff-Kischner reaction) to 4-phenylbutanoic acid. Ring closure is achieved by heating in polyphosphoric acid (PPA). The product is 1-tetraione and reduction of the carbonyl group then gives 1,2,3,4-tetrahydronaphthalene (tetralin). Aromatization is achieved by dehydrogenation over a palladium catalyst. 

The thermolysis of (225) and related compounds, superior in yields to the acid ring-closure via (219) to (221), opens a general way for pyridoannelation of structurally appropriate, also acid-sensible amino derivatives of aromatic and heterocyclic compounds. 

Derivation Condensing phthalic anhydride and chlorobenzene in the presence of anhydrous aluminum chloride to form p-chlorobenzoylbenzoic acid. Ring closure of the intermediate acid is brought about by heating in sulfuric acid solution. 

Scheme III. Quinacridone via polyphosphoric acid ring closure.

Loss of tritium originally present at C-2 of methionine can be accounted for if 4-amino-2-ketobutyric acid is an intermediate derivable from 2,4-diaminobutyric acid. Ring closure of the amino-ketone would give azetine-2-carboxylic acid... 

Phosphoric acid formic acid Ring closure in y -position to nitrogen Azepine ring... 

The construction of muscone can be explained in this way the multienzyme complex of fatty acid biosynthesis is initiated with acetyl-CoA. Then one propi-onyl-CoA unit is incorporated, followed by six further acetyl-CoA units, resulting in the mono-branched (14S)-methylpalmitic acid. Ring closure forms an analogue of civetone. [164]... 

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