Heterocyclic compounds from 3,3-dimercapto-1 -aryl-2-propen-1-ones. Note 2. Condensation with o-aminothophenol and o-aminophenol

The condensation of 3,3-dimercapto-1-phenyl-2-propen-1-one with o-aminothiophenol and o-aminophenol in hot xylene gave 2-phenacylbenzothiazole ( 3 ) and 2-phenacylbenzoxazole ( 5 ). When the reaction with o-aminophenol was carried out in hot benzene, 2-beuzoylthioacctamidophenol ( 4 ) was obtained, which, heated in hot xylene gave 5. Ethyl benzoylacetale by reaction with o-aminothiophenol gave 3 , whereas by reaction with o-aminophenol gave no heterocyclic compound. However, we were able to isolate 2-benzoylacetamidophenol ( 6 ), ethyl β-phenyl-β-(o-hydroxy)phenyliminopropionate ( 7 ), and 2-[β-(o-hydroxy)anilino] cinnamoylamidophenol ( 8 ). Ir and nmr spectra of synthesized compounds point out the existence of tautomers.     

9-Hydroxy-2-methyl-4H-pyrido[1,2-α] pyrimidin-4-one and its derivatives

2-Amino-3-(o-bromobenzyloxy)pyridine ( 1 ) and ethyl acetoacetate gave 9-(o-bromobenzyl-oxy)-2-methyl-4H-pyrido[1,2-α]pyrimidin-4-one ( 2 ) in 2% yield. When 1 and methyl β-amino-crotonate ( 3 ) were reacted, benzyl ether cleavage occurred and the products were 9-hydroxy-2-methyl-4H-pyrido[1,2-α]pyrimidin-4-one ( 4 ) and its ammonium salt ( 5 ). These observations led to an alternative synthesis in which 2-amino-3-pyridinol ( 6 ) and either 3 or methyl acetoacetate, ( 8 ) in diethylbenzene at 185° gave 4 in 86 and 87% yields, respectively, and the anion of 4 and o-bromobenzyl bromide gave 2 in 61% yield. Even in diethylbenzene at 185°, 1 and 8 gave only trace amounts of 2 . Thus, o-bromobenzylation of the 3-hydroxyl group in 6 markedly decreased the reactivity of the amino group in 6 toward reactions with acetoacetic esters.     

Dérivés de sucres benzimidazoliques et benzothiazoliques

Benzimidazole and benzothiazole sugar derivatives Simple aldehydosugars such as 1 or 2 , by reaction with o-phenylenediamine, gave the corresponding benzimidazoles 3 and 4 . Whereas the unperturbed α, β-unsaturated aldehydosugar D gave the benzodiazepine E upon treatment with o-phenylenediamine, the formyl-bearing alkenyl acetals 5 and 8 led, in the same conditions, to the benzimidazoles 6 and 9 respectively or, on reaction with o-aminothiophenol, to the benzothiazoles 7 and 10 respectively. This difference in reactivity is explained by the electrondonor ability of the oxygen atom of the alkenyl acetal function as shown by the ¹³C-RMN. spectra.     

Reaction of 3-(o-chlorobenzylidene)-2,4-dioxopentanoic acid with hydroxylamine hydrochloride. Revised structure tor azeto[3,2-d]isoxazoline

Reaction of 3-(o-ehlorobenzylidene)-2,4-dioxopentanoic acid (1) with hydroxylamine hydro-chloride in acetic acid gave 5-(o-chlorophenyl)-3-methyl-4-(α-hydroxyimino)isoxazolineglyo-xylic acid (5) and 3-(o-chlorobenzylidene)-4-hydroxyimino-2-oxopentanoic acid (2) in 57% and 7% yields. Pyrolysis of 5 afforded 5-(o-chlorophenyl)-3-methylisoxazole-4-carbonitrile (8), cis- and trans-5-(o-chlorophenyl)-3-methylisoxazoline-4-carbonitriles (9,10), and 5-(o-chloro-phenyl)-3-methylisoxazoline-4-carboxamide (11).     

Acetylenic chemistry: Part 13. Synthesis of oxazoles and oxazoloquinazolines from o-amino-N-(1,1 -disubstituted-propynyl)benzamide

Conversion of isatoic anhydride to o-amino-N(1,1-disubstituted-propynyl)benzamides 3a-c followed by reflux in ethanolic potassium hydroxide gave 2-(o-aminophenyl)-4,4-disubstituted-5-methylene-4H-oxazoles 4a-c . The treatment of same 3a-c with triphosgene in pyridine with subsequent reflux gave 4a-c and 2-methylene-3,3-disubstituted-oxazolo[2,3-b]quinazolin-5(3H)-ones 5a-c.     

Synthesis,Structures, and Properties of Novel N‐Aryl‐phenanthren‐o‐iminoquinones

The interaction of 9,10‐phenanthrenquinone with primary amines has been studied. Use of sterically hindered anilines gave the phenanthren‐o‐iminoquinones in good yields. These compounds are structural analogues of o‐benzoquinones. Using single‐electron reduction, o‐iminoquinones may synthesize metal's free‐radical complexes.     

The synthesis of 1,3,4,5-tetrahydro-2,3-benzoxazepines and 1,2,4,5-tetrahydro-3,2-benzoxazepines

Condensation of o-bromomethylphenethyl bromide with potassium salt of N-hydroxyurethan afforded 3-earbethoxy-1,3,4,5-tetrahydro-2,3-benzoxazepine, which was hydrolyzed to 1,3,4,5-tetrahydro-2,3-benxoxazepine (III). The reaction of o-aeetoxymethylphenethyl bromide (VIb) with potassium salt of N-hydroxyurethan in DMF, gave a complex mixture, from which O-[2-(o-acetoxymethylphenyl)(ethyl]-N-earbethoxyhydroxylamine (VIIa) was separated. Subsequent desacetylation to VIIb and halogenation yielded O-[2-(o-bromomethylphenyl)ethyl]-N-carbethoxyhydroxylamine (VIIc). By treatment of VIIc with potassium hydroxide, 2-carbethoxy-1,2,4,5-tetrahydro-3,2-benzoxazepine (X) was obtained together with small amounts of 6,15-diearbethoxy-5,6,8,9,14,15,17, 18-octahy drodibe nzo[d,I]-1,8-dioxa-2,9-diazaeyclotetradec in e (XI). Hydrolysis of X with potassium hydroxide gave 1,2,4,5-tetrahydro-3,2-benzoxazepine (XII). N-Alkyl and N-acyl derivatives of III and XII were also prepared.     

The molecular structure and chemical reactivities of the condensation products of o-substituted benzylidenacetylacetone with hydrazine dihydrochloride

Reaction of o-nitrobenzylideneacetylacetone ( 1a ) with hydrazine dihydrochloride in methanol gave 4-(α-methoxy-o-nitrobenzyl)-3,5-dimethylpyrazole hydrochloride ( 4a ), whose structure was unambigously confirmed by an X-ray crystallographic analysis, via 4-(o-nitrobenzylidene)-3,5-dimethylisopyrazole ( 2a ). Compound 2a was synthesized by condensation of 1a with hydrazine dihydrochloride in acetonitrile. Analogously the corresponding o-chloro derivatives ( 2b, 4b ) were obtained. These were converted to N-methyl ( 6b ) and N-acetyl ( 7a,b ) derivatives and the behaviors on bromination and pyrolysis were investigated.     

Reaction of 1,3‐dicarbonyl compounds with o‐phenylenediamine or 3,3′‐diaminobenzidine in water or under solvent‐free conditions via microwave irradiation

Reaction of ophenylenediamine with β‐diketones or β‐ketoesters in water formed 2‐substituted benzimi‐dazoles. Reaction of 3,3′‐diaminobenzidine gave similar results. Under microwave irradiation conditions solvent‐free reaction of o‐phenylenediamine with β‐ketoesters afforded l,5‐benzodiazepin‐2‐one derivatives. An exception is the reaction of o‐phenylenediamine with ethyl acetoacetate under microwave irradiation, which gave 2‐methylbenzimidazole.     

Pyrido[2′1′:2,3]imidazo[4,5-c]isoquinoline and the alkylation of pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolin-5(6H)-one

The reaction of 2-aminopyridine, o-phthaldehydic acid and potassium cyanide gave pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolin-5(6H)-one, which upon treatment with propargylbromide, yielded both O and N alkylated products. 2-Aminopyridine, o-phthaldehyde and potassium cyanide gave 1-cyano-2-(2-pyridyl)isoindole which rearranged in acid to give the previously unreported parent pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinole. Structures were confirmed using uv, ir, nmr and x-ray spectroscopy.     

A new synthesis of novel 1-aryl-3-heteroaryl-1H-pyrazolo[3,4-b]quinoxalines via a Key Intermediate

The chlorination of the α-hydrazonoester 4 with phosphoryl chloride/pyridine gave 3-[α-(o-chlorophenylhydrazono)methoxycarbonylmethyl]-2-chloroquinoxaline 5 , whose cyclization with 1,8-diazabicyclo[5,4,0]-7-undecene afforded 3-methoxycarbonyl-1-(o-chlorophenyl)-1H-pyrazolo[3,4-b]quinoxaline 6 . The reaction of 6 with hydrazine hydrate provided 3-hydrazinocarbonyl-1-(o-chlorophenyl)-1H-pyrazolo[3,4-b]quinoxaline 7 , whose reactions with methyl and allyl isothiocyanates furnished 3-(2,3-dihydro-4-methyl-3-thioxo-4H-1,2,4-triazol-5-yl)-1-(o-chlorophenyl)-1H-pyrazolo[3,4-b]quinoxaline 2 and 3-(4-allyl-2,3-dihydro-3-thioxo-4H-1,2,4-triazol-5-yl)-1-(o-chloropheny)-1H-pyrazolo[3,4-b]quinoxaline 8 , respectively. Moreover, the reactions of 7 with triethyl orthoformate and orthoacetate gave 1-(o-chlorophenyl)-3-(1,3,4-oxadiazol-5-yl)-1H-pyrazolo-[3,4-b]quinoxaline 9a and 1(o-chlorophenyl)-3-(2-methyl-1,3,4-oxadiazol-5-yl)-1H-pyrazolo[3,4-b]quinoxaline 9b , respectively.     

Reinvestigation of the synthesis of 5-arylamino-2-picolines

Reaction of 5-bromo- or 3-bromo-2-methylpyridine with o-nitroaniline gave the corresponding N-[2-methyl-5(or 3)pyridyl]-o-nitroanilines. Reduction to the corresponding amino derivatives and ring closure to 1-[2-methyl-5(or 3)pyridyl]benzotriazole allowed the structures to be confirmed and an earlier literature report to be corrected. Displacement of bromide by anthranilic acid from 5-bromo-2-methylpyridine and decarboxylation gave N-(2-methyl-5-pyridyl)aniline.     

New Quinoline Derivatives on the Basis of (4-Hydroxy-2-methylquinolin-3-yl)acetic Acid

A procedure was developed for the synthesis of (4-hydroxy-2-methylquinolin-3-yl)acetic acid and the corresponding acyl chloride. Reactions of the latter with o-aminobenzenethiol, o-phenylenediamine, o-aminophenol, anthranilic acid, and thiosemicarbazide gave, respectively, 2-(4-hydroxy-2-methylquinolin-3-ylmethyl)-1,3-benzothiazole, -benzoxazole, -benzimidazole, 2-(4-hydroxy-2-methylquinolin-3-ylmethyl)-4H-3,1-benzoxazin-4-one, and 4-hydroxy-2-methyl-3-(5-sulfanyl-1H-1,2,4-triazol-3-ylmethyl)quinoline.     

Mononuclear heterocyclic rearrangements. Part 12. Rearrangement of 1,2,4-oxadiazoles into indazoles

The first example of a mononuclear heterocyclic rearrangement involving an XYZ = CCN side-chain sequence is reported. The 3-(o-aminophenyl)-, and 3-(o-methylaminophenyl)-5-methyl-1,2,4-oxadiazoles ( 3a,b ) gave a thermally induced rearrangement into 3-acylaminoindazoles ( 4a,b ). On the other hand, the 3-(o-acetylaminophenyl)-5-methyl-1,2,4-oxadiazole ( 3c ) produced a base induced rearrangement into 3-acetylaminoindazole ( 4a ).     

On the reactions between ethyl benzoylacetate and anisidines

4-Hydroxy-7-methoxy-3-[(m-methoxyphenylimino)-phenylmethyl]-2-quinolone ( 6 ) was a by-product of the condensation of ethyl benzoylacetate and m-anisidine; no corresponding products were obtained from p- and o-anisidine. From o-anisidine, 2-phenyl-8-methoxy-4-quinolone ( 1c ) was isolated and characterized; the same reaction also gave 2-phenyl-4-o-anisidyl-1-8-methoxy-quinoline ( 11 ) and the Schiff base ( 14 ) as by-products; the crotonamide (15) also isolated, is a possible intermediate of the cyclization. The direct condensation of anisidines with ethyl benzoylacetate in diphenyl ether and the transformations of some intermediates were studied.     

Synthesis and alkylation of 3,4-dihydro-1H-1,3-4-benzotriazepine-2,5-diones and related systems

A synthesis of the 1,3,4-benzotriazepine-2,5-dione 2a and its 2-thio analog 11 is described. The key step was the mild and efficient cyclization of the o-(aminobenzoyl)hydrazine 10 , obtained from the reaction of a protected hydrazine derivative with the o-nitrobenzoyl chloride 3 . Alkylation of 2a takes place exclusively at N -3 while alkylation of 11 takes place on sulfur. Cyclization of the o-(aminobenzoyl)hydrazine 14 gave the 2,4(1H,3H)-quinazolinedione 15 as the sole product.     

Perhaloketones XIX . Derivatives of benzo-N-heterocycles

A study was made of the behavior of imidazole and six benzo-N-heterocyclic compounds upon direct treatment with anhydrous and hydrated hexafluoro- and sym-tetrafluorodichloroacetones. Two of the compounds did not react, and four gave addition compounds. Indole reacted with both ketones in the 3-position. Heterocyclic precursors were made by reacting o-phenylenediamine, o-aminophenol, and o-aminobenzenethiol with hexafluoroacetone hydrate, thus introducing the 2-hydroxyhexafluoro-2-propyl moiety into the ring para to the amino group. A similar product was made from o-phenylenediamine and tetrafluorodichloroacetone. These compounds were then converted to twenty-eight heterocyclic derivatives. Four of the latter underwent haloform cleavage of the hydroxyhexahalopropyl group, a novel, but not widely applicable, preparative approach to the corresponding heterocyclic carboxylic acids.     

Synthesis of magnesium catecholate and <Emphasis Type="Italic">o</Emphasis>-semiquinone complexes by oxidation of the metal with 3,6-di-<Emphasis Type="Italic">tert</Emphasis>-butyl-<Emphasis Type="Italic">o</Emphasis>-benzoquinone

Oxidation of amalgamated magnesium metal with 3,6-di-tert-butyl-o-benzoquinone (1) in different aprotic organic solvents afforded magnesium catecholate and bis-o-semiquinolate complexes. The catecholate derivatives of magnesium CatMgL₂ (Cat is the 3,6-di-tert-butyl-o-benzoquinone dianion, L = THF or Py) were synthesized in high yields in pyridine and tetrahydrofuran, respectively. The reactions in diethyl ether or dimethoxyethane produced hexacoordinated metal bis-o-semiquinolates SQ₂MgL_n (SQ is the 3,6-di-tert-butyl-o-benzoquinone radical anion, L = Et₂O, n = 2; L = DME, n = 1). The reaction with the use of toluene as the solvent gave a magnesium bis-o-semiquinolate complex containing the coordinated unreduced o-quinone molecule. The molecular structures of the [CatMgPy₂]₂ and SQ₂Mg·DME complexes were established by X-ray diffraction. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 92–98, January, 2007.     

Well‐defined NHC?Pd complex‐mediated intermolecular direct annulations for synthesis of functionalized indoles (NHC = N‐hetero‐cyclic carbene)

As alternatives to the common tertiary phosphine/Pd systems, well‐defined N‐heterocyclic carbene–Pd complexes have been proven to be highly efficient precatalysts for intermolecular direct annalution of o‐haloanilines and ketones at lower catalyst loadings. A highly efficient and practical protocol for synthesis of functionalized indoles was developed using (IPr)Pd(acac)Cl as catalyst. Both o‐bromoanilines and o‐chloroanilines gave rise to efficient coupling under the reaction conditions. Related to acyclic ones, cyclic ketones coupled more effectively with o‐haloanilines. With [Pd(IPr)₂] as catalyst, the base‐sensitive groups including OH and CO₂H groups could be tolerated. Copyright © 2011 John Wiley & Sons, Ltd.     

Stability of the Ion Pair Between Ca<Superscript>2+</Superscript> and 2-(Hydroxymethyl)-3-Deoxy-D-<Emphasis Type="Italic">erythro</Emphasis>-Pentonate (α-Isosaccharinate)

Ion-pair formation between Ca²⁺ and -isosaccharinate, Ca²⁺ + ISA^-CaISA⁺, was studied by two independent methods: an ion-exchange and a potentiometric method (Ca-selective electrode). The two methods gave similar values for the complexation constant, log K_CaISA+^o at I = 0, (22 ± 1)°C. The ion-exchange method gave a value of log K_o^CaISA+ = (1.8 ± 0.1) and the potentiometric method resulted in logK_CaISA+^o = (1.78 ± 0.04). These values are in good agreement with the estimated value, log K_CaISA+^o = 1.7, based on the formation of a Ca-gluconate ion pair.