Heterocycles from substituted amides. VIII Oxazole derivatives from reaction of isocyanates with 2-isocyanoacetamides

A facile reaction of 2-isocyanoacetamides 1 with reactive aryl and sulfonyl isocyanates is shown to give 5-amino-2-oxazolecarboxamides 3 in a reaction arising from electrophilic attack of isocyanate with the nucleophilic isocyanide carbon. This reaction, perhaps proceeding through an unstable nitrile ylid intermediate reminiscent of the Cornforth rearrangement, is a first example of ring closure via acylation, involving the activated methylene of an organic isocyanide, without recourse to added base. Isomeric 5-amino-4-oxazolecarboxamides 4 are formed when 5-aminooxazoles 2 react with isocyanates. Since 2 has previously been shown to easily form by thermal isomerization of 1 , methods now exist for the preparation of both 5-amino- 2- and 4-oxazolecarboxamides from the single starting material 1 . In contrast, 1 with acyl isocyanates is shown to give a variety of products, including iminooxazolinediones, 5-amino-2-oxazolecarbox-amide 3 and 2 (1) pyrazinones (tentatively identified), depending on the structure of the isocyanates.     

Heterocycles from substituted amides. VI. A new carbostyril synthesis from alpha-substituted acetamides and the vilsmeier reagent

Reaction of tertiary α-substituted acetanilides with Vilsmeier reagent has been found to give 1,3-disubstituted-carbostyrils, 1. α-Chloro-N-(1-cyclohexen-1-yl) acetamides are similarly converted to tetrahydro carbostyrils 2 and 3. The method appears useful for the preparation of a variety of 1,3-substituted 2(1H) quinolinones. The scope and mechanism of the reaction has been investigated, with evidence presented to indicate the ring-closure proceeds via electrophilic attack of Vilsmeier reagent on intermediate chlorenamine.     

Heterocycles from substituted amides,V.. 1,2,3,5-Oxathiadiazolin-4-one 2-oxides from thionyl chloride and N-hydroxyureas

The reaction of certain N-hydroxy-N-methyl-N′-aryl ureas, 2 , with thionyl chloride are shown to give a new heterocycle, 1,2,3,5-oxathiadiazolin-4-one 2-oxides, 3 , in a synthesis that appears to have more severe structural requirements than the previously reported ring closures from α-hydroxyacylanilides and thionyl chloride. Isolable amounts of 3 are obtained only if the aryl group contains deactivating substituents, and the hydroxy group is attached to the N-alkyl nitrogen; otherwise, resin formation or ring chlorination are found to occur. The assigned structure as 3 was verified by a full three dimensional X-ray analysis of a representative example, 3a , 3-(4-bromophenyl)-5-methyl-1,2,3,5-oxathiadiazolin-4-one.     

Heterocycles from substituted amides. IX. 4,5-dihydro-1,2,4-triazin-6-(1H)ones from 2-isocyanoacetates and hydrazine

The novel synthesis of 4,5-dihydro-1,2,4-triazin-6-(1H)ones, 2 , from 2-isocyanoacetates is described. This synthetic method allows the first synthesis of the unsubstituted parent ring sytem and, in general, gives 2 substituted in only the five position. The assignment of tautomeric structures ( 2 or 3 ) to the triazinone products was resolved by spectroscopic means.     

Heterocycles from substituted amides III. 1,2,3-Oxathiazolidin-4-one 2-oxides from thionyl chloride and α-hydroxyacylanilides

A new heterocyclic series was synthesized for the first time, from reaction of thionyl chloride with α-hydroxyacylanilides (1). Structural features of the resulting 1,2,3-oxathiazolidin-4-one 2-oxides (2) are discussed with particular reference to their spectral properties, and are compared with the previously reported 1,2,3-oxathiazolidine 2-oxides (3).     

Heterocycles from substituted amides II. Novel behavior of a reactive thiophene in some cyelo- and acyclo-addition reactions

N,N'-Diisopropyl-N,N'-diphenyl-2,4-thiophenediamine ( 1 ) has demonstrated its remarkable electron-donating abilities and atypical behavior as a thiophene, by its facile reaction with a number of electron deficient dienophiles. Thus, β-nitrostyrene, ethoxymethylene malononitrile, diethyl azodicarboxylate and dimethyl acetylenedicarboxylate undergo Michael-type addition at the 5-position of 1 to form adducts 2, 3, 4 , and 5 . Alternatively, the dienophiles, acrylonitrile, N-phenylrnaleimide and phenyl-1,2,4-triazoline-3,5-dione gave novel cyclic materials 6, 9 , and 11 , not necessarily arising from simple Diels Alder addition. Structure proofs for the products as well as alternative mechanisms for their formation are discussed.     

Sulfur substituted Small-ring Heterocycles

The synthesis of epoxy sulfines and sulfonyl azirines is described     

Hydrolysis ofN-aromatic substituted amides

Summary The hydrolysis ofN-aromatic substituted amides is usually done by refluxing with 50–70% sulphuric acid and then neutralising with alkali to obtain the amine. The apparatus used in this method will hydrolyse these amides in 8–20 minutes and the aromatic amine can be distilled in a pure form as the reaction proceeds. Aqueous acid or alkaline hydrolysis of amides and imides is preferable because the acid is obtained more easily from these reactions.

---

Zusammenfassung Die Hydrolyse N-substituierter aromatischer Amide erfolgt üblicherweise durch Erhitzen unter Rückfluß mit 50- bis 70%iger Schwefelsäure und darauffolgende Neutralisierung mit Alkali, um das freie Amin zu erhalten. Der hierfür verwendete Apparat ermöglicht die Hydrolyse innerhalb 8 bis 20 Minuten, wobei das reine Amin je nach Fortschreiten der Reaktion abdestilliert werden kann. Die Hydrolyse der Amide und Imide in wäßriger Säure oder Alkali ist vorzuziehen, da der Säureanteil dann leichter zu gewinnen ist.

---

Résumé On effectue couramment l'hydrolyse des amidesN-aromatiques substitués par reflux avec de l'acide sulfurique à 50–70% et ensuite neutralisation par une base pour obtenir Famine. L'appareil utilisé dans cette méthode permet l'hydrolyse de ces amides en 8 à 20 minutes et l'aminé aromatique peut être distillée à l'état pur pendant que la réaction s'effectue. L'hydrolyse des amides et des imides par un acide ou une base aqueuse est préférable car on obtient l'acide plus facilement dans ce cas.

     

Fluorine-Containing Heterocycles: VII. Nucleophilic Substitution in 6,7-Difluoroquinoxalines

For the purpose of biological screening, a number of new quinoxalines have been synthesized via fluorine replacement in 2,3-disubstituted 6,7-difluoroquinoxaline 1,4-dioxides and their deoxygenated derivatives by reactions with dialkylamines, sodium azide, and sodium methoxide.     

Heterocycles. Part I. A new route to the synthesis of substituted 2-aminopyrimidines

Heterocyclic aldehydes (A) reacted with alkyl aryl ketones (B) to give the corresponding 1,3-diaryl-2-propen-1-ones (Ia-1). Condensation of these chalcones with guanidine produced the corresponding 2-amino-4,6-diarylpyrimidines (IIa-1). The structure of all products was substantiated by chemical and spectroscopic methods.     

Synthesis of substituted 2-aminoquinoline-3-carboxylic acid amides

Substituted 3-(2-nitrophenyl)-2-cyanoacrylic acid amides were synthesized by the Knoevenagel reaction and were then reduced with iron in acetic acid to the corresponding 2-aminoquinoline-3-carboxylic acid amides.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1515–1517, November, 1988.     

Heterocycles from substituted semicarbazides and thionyl chloride. 1-oxo-1, 2,3,5-thiatriazolidin-4-one

Reaction of thionyl chloride and semicarbazides or thiosemicarbazides produces the novel 1-oxo-1,2,3,5-thiatriazolidin-4-one or 4-thione ring system.     

Heterocycles. IX. Synthesis of new substituted benzo[h]quinolones

2-Arylidine-1-tetralones I were condensed with phenyl-, p-chlorophenyl-, and p-methoxyphenylacetamides A in the presence of a base to yield the corresponding benzo[h]quinolones II-IV. Dehydrogenation of compounds II gave the benzoquinolones V which upon acetylation yielded the corresponding 2-acetyl derivatives VI. The structure of all products was substantiated by chemical and spectral methods.     

Heterocycles. Part VIII. Synthesis of new substituted benz[g]indazoles

Aryl aldehydes I reacted with α-tetralone to give the corresponding 2-arylidene-1-tetralone II. Condensation of the latter chalcones with hydrazine, methylhydrazine and phenylhydrazine produced the corresponding benzo[g]indazoles III, V and VI respectively. Acetylation of the 2H-benz[g]indazole derivatives III gave the corresponding 2-acetylated compounds IV. The structure of all products was elucidated by chemical and spectroscopic methods.