The preparation of heterocyclic materials from 2-isocyanatobenzoyl chloride and difunctional nucleophiles

2-Isocyanatobenzoyl chloride was treated with difunctional nucleophiles such as o-phenylenediamine, 1,8-diaminonaphthalene, o-aminothiophenol, and thioacetamide. The diaminonucleophiles gave intermediates which were thermally cyclized, and the other nucleophilic reagents gave heterocyclic materials directly.     

A new method of synthesis of some 2-aryl and 2-heterocyclic benzimidazole,benzoxazole and benzothiazole derivatives

A new one-step facile method for the synthesis of some benzimidazole, benzoxazole and benzothiazole derivatives is described. The method involves the action of aromatic and heterocyclic selenoamides on some o-phenylenediamine, o-aminophenol and o-aminothiophenol and their derivatives.     

Benzimidazole polymers from aldehydes and tetraamines

A new method for the preparation of benzimidazole polymers is described. The solution polymerization of aromatic tetraamines with isophthalaldehyde bis bisulfite adduct in N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAc), N-methyl-2-pyrrolidone (MP), and dimethyl sulfoxide (DMSO) produced polybenzimidazoles with viscosities (ηinh) in the range of 0.3–0.5 measured in formic acid solution. Also a model compound study with benzaldehyde, benzaldehyde diethyl acetal, and benzaldehyde bisulfite adduct with o-phenylenediamine was carried out. The results showed that the reaction of benzaldehyde bisulfite adduct with o-phenylenediamine in DMAc as the solvent gave quantitative yields of 2-phenylbenzimidazole. Excellent yields of 2-phenylbenzthiazole, 2-phenylbenzoxazole, and 2-pyridylbenzimidazole were also obtained with the benzaldehyde bisulfite adduct and picoline-2-carboxaldehyde bisulfite adduct with o-aminothiophenol, o-aminophenol, and o-phenylenediamine. The reaction conditions for the preparation of the polymers and the model compounds are very mild and the reaction times range from 15 min to 1 hr for the model compounds and 3–5 hr for the polymers. Longer reaction times did not increase the viscosities of the polymers to any extent.     

Nitrogen-containing heterocycles from metal β-diketonates

Factors determining the reaction of metal β-diketonates with hydrazine, in particular the nature of central metal ion and structure of β-diketonate ligand, are discussed. The possibility for the preparation of other heterocyclic compounds via reaction of metal acetylacetonates with phenylhydrazine, o-phenylenediamine, urea, and thiourea was studied.     

1,2,3-benzotriazines. I. The synthesis of some benzimidazo [1,2-c][1,2,3]-benzotriazines and naphth[1′,2,(2′,1′):4,5]imidazo[1,2-c][1,2,3]benzotriazine

A number of substituted benzimidazo[1, 2-c][1,2,3]benzotriazines were prepared by the diazotization of the appropriate 2-(o-aminophenyl)benzimidazoles. Diazotization of 2-(o-aminophenyl)naphth[1,2-d]imidazole yielded a new heterocyclic ring system. Various methods of preparation of 2 - (o-aminophenyl)benzimidazoles were investigated. The condensation of o-phenylenediamines with anthranilic acids, in the presence of polyphosphoric acid, provided a convenient route to 2-(o-aminophenyl)benzimidazoles but in several cases the products were contaminated with considerable amounts of 6-(o-aminophenyl)benzimidazo[1,2 -c]quinazolines. 2 - (o-Aminophenyl)benzimidazoles were also obtained by the catalytic hydrogenation of 2-(o-nitrophenyl)benzimidazoles which resulted from the condensation of an o-phenylenediamine with an o-nitrobenzaldehyde in ethanol, nitrobenzene or acetic acid. When the condensation was carried out in nitrobenzene, small amounts of 2-(o-aminophenyl)benzimidazoles were also formed. The Weidenhagen synthesis, which involves the reaction of an aromatic diamine with an aldehyde in the presence of copper acetate and subsequent decomposition of the cuprous salt of the benzimidazole, yielded 2-(o-aminophenyl)benzimidazoles instead of the expected 2-(o-nitrophenyl)benzimidazoles when the decomposition was carried out in ethanol. When the cuprous salt was treated with hydrogen sulfide in dilute hydrochloric acid, a mixture of amino- and nitrobenzimidazoles resulted. The ultraviolet and infrared spectra of all the compounds prepared were examined.     

A facile synthesis of unsymmetrical heterocyclic azines by cyclodesulfurization: Reaction of methyl arylalkylidenehydrazinecarbodithioates with diamines

A new and facile synthesis of unsymmetrical heterocyclic azines is described. Methyl arylalkylidenehydraz-inecarbodithioates, prepared by the condensation of ketones or aldehydes with methyl hydrazinecarbodithioate, were heated under reflux with various diamines in ethanol. Secondary diamines, such as N,N′-dimethyl-ethylenediamine, N,N′-dimethyl-1,3-diaminopropane or N,N′-dimethyl-o-phenylenediamine, reacted smoothly with loss of hydrogen sulfide to give good yields of unsymmetrical azines. However, primary diamines, such as ethylenediamine or o-phenylenediamine, and primary/secondary diamines, such as N-methylethyl-enediamine and N-methyl-1,3-diaminopropane gave, instead, only the corresponding uncyclized thiosemi-carbazones. A cyclodesulfurization mechanism for azine formation is discussed.     

Synthesis and structure of reaction products obtained from 1,2-epoxyperfluorobutane and bifunctional nucleophilic reagents

1,2-Epoxyperfluorobutane readily reacts with bifunctional nucleophilic reagents to provide heterocyclic compounds with a pentafluoroethyl substituent. The reaction of this epoxide with thiourea and acetone thiosemicarbazone gave rise to 2-amino-5-pentafluoroethyl-5-fluoro-4(5H)-thiazolinone and 2-isopropylidenehydrazono-5-pentafluoroethyl-5-fluoro-4-thiazolidinone respectively. The reaction of 1,2-epoxyperfluorobutane with o-phenylenediamine and 2,3-diaminonaphthalene afforded in high yields 3-pentafluoroethyl-2(1H)-quinoxalinone and 3-(pentafluoroethyl)benzo[g]-2(1H)-quinoxalinone. The molecular and crystal structure of the obtained fluorine-containing heterocycles was established by XRD analysis.

     

Synthesis of new spirobenzazolines including a furo[3,4-b]pyran ring system

A series of 4,5-dihydrofuro[3,4-b]pyran-6-spiro-2′-benzazolines 3 were prepared by reaction of 4,4-dimethyl-2,6-dioxo-4,5-dihydrofuro[3,4-b]pyran 1 with o-phenylenediamine, o-aminophenol, o-aminothiophenol or their derivatives. Most of these compounds exhibited a significant analgesic activity.     

Reactions of 1,2-bis(trifluoroacetyl)benzene with nucleophiles leading to heterocyclic compounds

The reaction of 1,2-bis(trifluoroacetyl)benzene (II) with ammonia, hydrazine, hydroxylamine and L-alanine has been investigated and the resulting heterocyclic compounds fully characterized on the basis of spectral data. The reaction of II with $\text{o}$-aminophenol and $\text{o}$-phenylenediamine led to the formation of tetracyclic compounds XI and XII respectively. The structure of compound XII has been further supported by single crystal X-ray crystallography. Our studies reveal the potential of the diketone II as a valuable synthon for the synthesis of a variety of heterocyclic systems with trifluoromethyl substituents.     

Substituted γ-lactones. XXX. Reactions of α-Keto-β-Subtituted-γ-butyrolactones with diamines

The condensation reaction between α-keto-β-aroyl (or acyl) -γ-butyrolactones, 4a-4e and o-phenylenediamine or 2, 3-diaminonaphthalene leads under retrograde aldol condensation involving loss of formaldehyde to formation of 3-substituted-3, 4-dihydro-2 (1H) quinoxalinones or benzo [g] quinoxalinones, 7a-7g , respectively as a new convenient synthesis of this type of heterocyclic systems. The reaction of type 4 compound with 4, 5-diaminopyromidine, 8 , was found to proceed differently. 2-[(4-Amino-5-pyrimidinyl)amine]-4-oxo-3-(hydroxymethyl)-4-phenyl-2-butenoic acid 9 was the only product formed when the reaction between 4a and 8 was run in ethanol. The same reaction in glacial acetic acid proceeds with loss of formaldehyde, to afford 7-phenacylidene-7,8-dihydro-6 (1H)-pteridione 10 . The reaction between type 4 compounds and ethylenediamine or 1, 4-phenylenediamine leads to the formation of the bis-condensation products 13–15 , respectively.     

Synthesis of some benzimidazole,benzoxazole and benzothiazole derivatives. Action of aliphatic selenonesters on some o-phenylenediamine,o-amino-phenol and o-aminothiophenol and their derivatives

Aliphatic selenonesters react with o-phenylenediamine, o-aminophenol and o-aminothiophenol and their derivatives to form benzimidazole, benzoxazole and benzothiazole derivatives, respectively. The mass and nmr spectra of the mentioned compounds were studied.     

Reactions of N-substituted 3-azabicyclo[3.3.1]nonan-9-ones with N,N-, N,S-, and N,O-binucleophiles

Condensation of N-substituted 3-azabicyclo[3.3.1]nonan-9-ones with difunctional N,N-, N,S-, and N,O-centered nucleophiles (o-phenylenediamine, 1,2-diphenylethane-1,2-diamine, 2-aminobenzenethiol, cysteine, 2-aminophenol, serine) gave the corresponding spiro heterocyclic compounds fused at the C⁹ atom. Treatment of N-tert-butoxycarbonyl-substituted spiro compounds with anhydrous hydrogen chloride resulted in elimination of the tert-butoxycarbonyl group with formation of spiro[3-azabicyclo[3.3.1]nonane-9,2′-azole] hydrochlorides.     

Heterocyclic compounds from 3,3-dimercapto-1-aryl-2-propen-1-ones. Note 1. 4-Ary1-1,3-dihydro-2H-1,5-benzodiazepine-2-thiones

A series of new 4-aryl-1,3-dihydro-2H-1,5-benzodiazepine-2-thiones ( 3 ) has been synthesized by condensing the 3,3-dimercapto-1-aryl-2-propen-1-ones with o-phenylenediamine. The structure was established by the results of acid cleavage and by nmr spectra. The alkylation of compounds 3 gave 2-alkylthio-4-aryl-3H-1,5 benzodiazepines ( 10 ).     

Efficient Method for the Synthesis of Benzimidazoquinazoline Derivatives with Three‐Point Diversity

An efficient strategy for the preparation of a novel heterocyclic ring system of benzimidazoquinazolines with three‐point diversity has been described. The compounds were obtained by treating o‐phenylene diamines with o‐nitrobenzaldehyde to give benzimidazoles, followed by reduction of the nitro group to give an amine. Derivatization of the resulting amine with isothiocyanates followed by in situ cyclodesulfurization at rt furnished the title compounds in high yields and purities.     

Syntheses and transformations of substituted benzazolyl- and tetrazolyl(benzotriazol-1-yl)methanes

Condensation reactions of o-hydroxy- and o-mercaptoanilines, and o-phenylenediamine with (benzotriazol-1-yl)acetic acid result in (1,3-benzazol-2-yl)(benzotriazol-1-yl)methanes. Cycloaddition of sodium azide to (benzotriazol-1-yl)acetonitrile leads to (1,2,3,4-tetrazol-5-yl)(benzotriazol-1-yl)methane. The diazolo-substituted benzotriazolylmethanes thus obtained were mono- and di-alkylated at the methylene group and the displacement of the benzotriazole group by nucleophiles was investigated.     

Heterocycles from Pyrazoloylhydroximoyl Chloride: Synthesis of Certain Quinoxaline,Benzothiadiazine, Benzoxadiazine,Quinazolinone, Imidazo[1,2-a]pyridine,Imidazo[1,2-a]pyrimidine,Isoxazole, Pyrazolo[3,4-d]pyridazine and Pyrrolidino[3,4-d]isoxazolin-4,6-dione Derivatives

3-Ethoxycarbonyl-5-methyl-1-(4-methylphenyl)-4-pyrazoloylhydroximoyl chloride (1) reacted with o-phenylenediamine, o-aminothiophenol, o-aminophenol and methyl anthranilate to afford 3-nitrosoquinoxaline, benzothiadiazine, benzoxadiazine, and 3-hydroxyquinazoline, respectively. Imidazo[1,2-a]pyridine, imidazo[1,2-a]pyrimidine and isoxazole derivatives were obtained via the reaction of 1 with 2-aminopyridine, 2-aminopyrimidine and the appropriate active methylene compounds, respectively. Pyrazolo[3,4-d]pyridazines, and pyrrolidino[3,4-d]isoxazolines derivatives were also synthesized. The structures of the newly synthesized compounds were established on the basis of spectral data and alternate synthesis whenever possible.     

Substituted γ-lactones: On the structural elucidation of the reaction products from 4-aroyl-3-hydroxy-2(5H)-furanones and 1,2-diamines

The reaction pathway of 4-aroyl-3-hydroxy-2(5H)-furanones 1 with diamines depends on the nature of the amine as well as on the applied reaction conditions. Thus, the reaction of 1a-d with 5,6-diamino-1,3-dimethyluracil 5 led to the formation of two isomeric Schiff bases 7a-d and 8a-d . Conversely type 1 compounds reacted with 4,5-diaminopyrimidine 9 or 2,3-diaminopyridine 10 to form the mono acid-base adducts 11a and 11b respectively. When type 1 compounds were reacted with aliphatic diamines 13a-d or p-phenylenediamine and p-xylenediamine, respectively also an immediate formation of acid-base adducts 15a-f was observed. The reaction of a number of O-methylated type 1 compounds with 1,2-ethylenediamine afforded the novel seven-membered ring compounds 18a-d in good yields. The analogous reaction of O-alkylated 1a with o-phenylenediamine 2 or 2,3-diaminonaphthalene gave the expected tricyclic ring systems 19 or 20 .     

Heterocyclic o-Chloroaldehydes as Synthons in Organic and Inorganic Sulfur Chemistry

Abstract

Many heterocyclic o-chloroaldehydes are easy to prepare, for example via the Vilsmeier chloroformylation reaction. Due to the electron withdrawing effect of the formyl group, the halogen atom is normally a nucleofuge. This can be used to prepare a range of o-substituted heterocyclic aldehydes showing interesting rearrangement reactions. Such types of compounds are also useful as starting materials for the preparation of annelated heterocyclic systems.

We have demonstrated that heterocyclic mercapto groups can be protected as t-butylthioethers. Furthermore, we have found that thiolation of heterocyclic systems containing reactive halogen substituents can conveniently be carried out via the easily prepared t-butylsulfides.

This method has been used in the preparation of a number of N₂S₂-ligands. The resulting transition metal N₂S₂-complexes have been used in the study of model systems for one of the active sites in cytochrome c oxidase. The method also gives access to polymeric heterocyclic multisulfur transition metal complexes with high electrical conductivity.     

Synthesis of 4-Aryl-1,5-benzodiazepine-2-carboxamides

4,N-Diaryl-1,5-benzodiazepine-2-carboxamides were synthesized by acid-catalyzed reaction of (Z)-4,N-diaryl-2-hydroxy-4-oxo-2-butenamides with o-phenylenediamine or N,N'-bis(triphenylphosphoranediyl)-o-phenylenediamine. The reaction mechanism is discussed.     

Naphtho[1′,2′:5,6]pyrano[2,3–6][1,5]benzodiazepine Derivatives

The reaction of 3-(dimethylamino)-1-oxo-1H-naphtho[2,1-b]pyran-2-carbaldehyde (Ia) with o-phenylenediamines or N-monosubstituted o-phenylenediamines in refluxing glacial acetic acid afforded the corresponding naphtho[1′,2′:5,6]pyrano[2,3-b][1,5]benzodiazepin-15-(8H)ones V in very good yields. A similar result was achieved when the reaction was carried out in refluxing pyridine, using N-monosubstituted o-phenylenediamine hydrochlorides. The isolation of a significant intermediate as well as the synthesis through a different univocal pathway confirmed the structure of the compounds V. Moreover the reaction of Ia with N-monosubstituted o-phenylenediamines in refluxing pyridine generally afforded only low yields of compounds V, sometimes together with naphtho[1′,2′:5,6]pyrano[2,3-b][1,5]benzodiazepin-15-(13H)ones VII, isomers of V.