6(5H)-phenanthridinones. III. halo-6(5H)phenanthridinones

Halogenation of 6(5H)-phenanthridinone or its 3,8-dihalo derivatives with N-bromo or N-chlorosuccinimide in dimethylformamide gives the corresponding 2-halophenanthridinones (I,V,XI-XIV). Further halogenation of 2-halo-6(5H)-phenanthridinone with the appropriate N-halosuccinimide, in the same medium, gives the corresponding 2,4-dihalo derivatives (II,VI). NXS/DMF is found to be a very convenient halogenating system in these preparations. 1,3,8-Trihalo-6(5H)-phenanthridinones (XIX,XX) are prepared from the 1-nitro derivatives which are obtained by a Schmidt rearrangement of 2,7-dihalo-4-nitro-9-oxofluorenes. Similarly, rearrangement and further reaction of 2-nitro-5-chloro-9-oxofluorene (XXI) leads to 3,10-dichloro-6(5H)-phenanthridinone (XXIV). UV absorptions as well as selected IR absorptions of these 6(5H)-phenanthridinones are described.     

Nitrogen bridgehead compounds. Part 85. Synthesis and reactivity of 3,4-dihydro-1H,6H[1,4]oxazino[3,4-b]quinazolin-6-ones

3,4-Dihydro-1H,6H-[1,4]oxazino[3,4-b]quinazolin-6-one 3 and its 1-methyl and 1-hydroxy derivatives 8 and 13 were prepared by different routes. The active methylene group of compound 3 was reacted with electro-hilic reagents (bromine, phenyldiazonium chloride, nitrous acid, a Vielsmeier-Haack reagent, aromatic aldehydes and diethyl oxalate) to yield 1-substituted-3,4-dihydro[1H,6H)-1,4-oxazino[3,4-b]quinazo-lin-6-ones. The reactivity of 1-hydroxy and 1-bromo derivatives 13 and 15 were also investigated in some reactions. The 3,4-dihydro-lH,6H-[1,4]oxazino[3,4-b]quinazolin-6-ones were characterized by means of uv, ¹H and ¹³C nmr spectroscopy.     

Synthesis of novel bis(chromenes) and bis(chromeno[3,4-C]pyridine) incorporating piperazine moiety

Novel bis(2-oxo-2H-chromene) as well as bis(2-imino-2H-chromene) derivatives incorporating piperazine moiety were prepared by the cyclocondensation reaction of bis(2-hydroxybenzaldehyde) with two equivalents of each of the appropriate β-ketoesters or acetonitrile derivatives. The bis(2-imino-2H-chromene-3-carbothioamide) derivative was used as a key synthon for construction of novel bis(3-(4-substituted thiazol-2-yl)-2H-chromen-2-one) derivatives via its cyclocondensation with a series of the appropriate α-halocarbonyl derivatives. Moreover, the bis(2-hydroxybenzaldehyde) reacted with four equivalents of the appropriate acetonitrile derivatives to afford the corresponding bis(3H-chromeno[3,4-c]pyridine) derivatives. Elucidation of the structure of the novel bis(chromenes) bearing piperazine nucleus was established by the spectral data and elemental analyses.     

Pyranopyrazoles. II. Synthesis and reactions of 1H,6H-pyrano[2,3-c]pyrazol-6-ones

Various 1H,6H-pyrano[2,3-c]pyrazol-6-ones (III-XXIII) were obtained from β-keto esters and 1H-pyrazol-5-ones or hydrazines. Nitrations, chlorinations and brominations of these pyranopyrazoles were also carried out giving the corresponding derivatives (XXIV-LXIV). The pyrone ring is the more reactive one in these reactions and the preferred position of attack is the 5-position. The substitution products are formed by the addition-elimination route.     

Synthesis of 6-amino and 6-ethoxy-2(1H)-pyridone derivatives

An efficient route allowing the synthesis of 6-amino and 6-ethoxy-2(1H)-pyridone derivatives by reaction of ethyl cyanoacetimidate, ethyl ethoxycarbonylacetimidate and related acetamidines with diethyl ethoxymeth-ylenemalonate (EMME) is reported. The formation of dienamino derivatives as intermediates and their heterocyclization to the 2(1H)-pyridone derivatives is described.     

6- And 7-Substituted 4H-Pyrido[1,2-a] pyrimidin-4-ones. Synthesis via the Acid-catalyzed Isomerization of 2-(Acetoacetamido)pyridines

A novel procedure has been developed for converting a variety of substituted 2-(aceto-acetamido)pyridines into substituted 4H-pyrido[1,2-a]pyrimidin-4-ones. The reaction involves an acid-catalyzed isomerization of the 2-(acetoacetamido)pyridine derivatives into the corresponding enamines, under conditions that permit the latter to undergo cyclization to the 4-one, in situ. The method has been employed to prepare a number of hitherto unknown 2,6- and 2,7-di- and 2,7,9-trisubstituted 4H-pyrido[1,2-a]pyrimidin-4-ones.     

Research on nitrogen containing heterocyclic compounds. XX. Synthesis of 8H-Imidazo[5,1-c]pyrrolo[1,2-a][1,4]benzodiazepine and its 6-derivatives

Starting from 1H-1-(2-aminomethylphenyl)pyrrole the synthesis of 8H-imidazo[5,1-c]pyrrolo[1,2-a][1,4]ben-zodiazepine, a novel nitrogen containing tetracyclic ring, has been performed by two routes involving a three-step and a six-step sequence, respectively. The more complex sequence offers the advantage to obtain also 3-alkyl and 3-aryl derivatives of the parent nucleus. The three step sequence involves the use of toluene-4-sulfonylmethylisocyanide (TosMIC) as a synthon.     

Aromatic nucleophilic substitution. Part 2. Preparation of novel 3-substituted xanthone and thioxanthone derivatives

The novel 3-nitro-9-oxo-9H-xanthene- and 3-nitro-9-oxo-9H-thioxanthene-l-carboxylic acids 2a–d were prepared by intramolecular acylation of 3-aryloxy- and 3-arylthio-5-nitrophthalic anhydrides 1 (Scheme). The 3-nitro group was readily substituted by O- and S-nucleophiles and halide and azide ions to give a range of 3-substituted thioxanthone derivatives 3 with varied λ_max.     

An Efficient Synthesis of Novel 2‐(5‐indolyl)‐1H‐benzimidazole Derivatives and Evaluation of Their Antimicrobial Activities

In this paper, we report the synthesis of novel 2‐(5‐indolyl)‐1H‐benzimidazole derivatives. The methodology involves the Sonogashira reaction of 4‐(1H‐benzimidazol‐2‐yl)‐2‐bromo‐N,N‐dimethylaniline ( 3 ) with variety of terminal alkynes to get corresponding novel 4‐(1H‐benzimidazol‐2‐yl)‐2‐alkynyl‐N,N‐dimethylaniline derivatives ( 4 ). These compounds on iodocyclization afforded novel iodoindolylbenzimidazole derivatives ( 5 ). The resulting compounds were functionalized further via palladium‐mediated carbon–carbon bond formation for generating novel structurally diversified heterocyclic compounds. All these newly synthesized compounds were evaluated for antimicrobial activity.     

1,3,5-Trisubstituted hexahydrotriazines as mannich reagents. III. Preparation and cleavage of 3,4-dihydro-6-hydroxy-3-substituted-2H-1,3-benzoxazine hydrochlorides

3,4-Dihydro-6-hydroxy-3-substituted-2H-1,3-benzoxazine hydrochlorides have been prepared by the reaction of hydroquinones with novel aminomethylating reagents prepared from 1,3,5-trisubstituted hexahydrotriazines. With these monooxazine hydrochlorides is formed an equal molar amount of an amine hydrochloride. Purification leads to low yields. This difficulty has been circumvented by the use of bis(alkoxymethyl)amines in the presence of anhydrous hydrogen chlorides. The monooxazines have been hydrolyzed to yield ortho-secondary aminomethylhydro-quinone derivatives.     

On triazoles. XXV. The reaction of methyl (5-amino-3-Q-1H-1,2,4-triazolyl)dithiocarbonates with amines

Different “functionalised” triazolylthioamides 3 and -thioureas 4 were synthesised. The ring closure of the ω-hydroxyalkylthioamides 3/2–5 led to the corresponding 2-thiazoline 5/2–4 and 5,6-dihydro-4H-1,3-thiazine 5/5 derivatives, respectively. Unexpectedly, the ring closure of the corresponding 2,2-dimethoxyethyl derivative 3/18 led depending on the reaction conditions to a thiazole derivative 6 or to its 1,2,4-triazolo[3,4-b]-1,3,5-triazepin-5(9H)-thione isomer 7 representing a novel ring system. To corroborate its structure 7 was methylated to the corresponding S-methyl derivative 8 . Spectroscopical evidence is given for the structure of derivatives 3–8 obtained.     

Azines and azoles: CXXIX. Synthesis,structure, and some reactions of 2-aryl-4-sulfanyl-6H-1,3-thiazin-6-ones

Reactions of 2-aryl-4-chloro-6H-1,3-thiazin-6-ones with sodium sulfide in aqueous alcohol at 18–20°C led to the formation of a readily separable mixture of 2-aryl-4-sulfanyl-6H-1,3-thiazin-6-one sodium salts (yield >70%) and bis(2-aryl-6-oxo-6H-1,3-thiazin-4-yl) sulfides (<10%). The latter can also be obtained in more than 50% yield by treatment of 2-aryl-4-sulfanyl-6H-1,3-thiazin-6-one sodium salts with 2-aryl-4-chloro-6H-1,3-thiazin-6-ones. Methylation of 2-aryl-4-sulfanyl-6H-1,3-thiazin-6-ones afforded the corresponding methylsulfanyl derivatives (yield >90%) regardless of the alkylating agent, solvent, temperature, reactant concentration, and their ratio. 2-Aryl-4-sulfanyl-6H-1,3-thiazin-6-ones in the crystalline state and in solutions in polar and nonpolar protic and aprotic solvents exist preferentially as 4-sulfanyl-6-oxo tautomers, and they undergo almost complete ionization in neutral aqueous, alcoholic, and aqueous-alcoholic media (pK _a = 4.3). Reactions of 4-sulfanyl-2-phenyl-6H-1,3-thiazin-6-one with ammonia, amines, and difunctional N-centered nucleophiles involve cleavage of the C⁶-S bond in the thiazine ring and subsequent recyclization of linear intermediates to pyrimidines and diazole derivatives. The structure of the isolated compounds was confiirmed by ¹H and ¹³C NMR, IR, and UV spectra.     

Purines, pyrimidines, and related fused systems. 20. Heterocyclizations of 6-alkynyl-1,3-dimethyllumazines. Synthesis of pyrrole and thiophene analogs of some natural pteridines

Sonogashira cross-coupling of 6-chloro-1,3-dimethyllumazine with terminal alkynes gave 6-alkynyl derivatives in good yields. Oxidative amination of the latter with primary alkylamines was accompanied by the pyrrole-ring closure to form 1-R"-2-R-6,8-dimethylpyrrolo[3,2-g]pteridine-5,7(6H,8H)-diones. The addition of bromine to 6-alkynyllumazines afforded the corresponding dibromoalkenes whose treatment with sodium trithiocarbonate gave rise to 2-R-6,8-dimethylthieno[3,2-g]pteridine-5,7(6H,8H)-diones. The latter compounds are close analogs of the metabolite of molybdenum cofactor (molybdopterine).     

Synthesis of some 2,3-Dihydro-11bH-thiazolo[3,2-d][1,4]benzoxazepin-5-(6H)one derivatives. A new heterocyclic ring system

Condensation of (S)-penicillamine methyl or ethyl ester hydrochloride with salicylaldehyde and its C-5 derivatives, provided the diastereomeric thiazolidine derivatives 1 and 2 . The resulting amino function was acylated to afford the amides 3 and 4. Cyclization of the latter led to the 2,3-dihydro-11bH-thiazolo[3,2-d]-[1,4]benzoxazepin-5-(6H)ones 5 and 6. Conformational data for these heterocyclic compounds are discussed.     

On triazoles XXXVIII. The reaction of isomeric 5-amino-3-morpholino-1H-1,2,4-triazolylcarbothiohydrazides with ortho esters

The reaction of isomeric differently methylated 5-amino-3-morpholino-1H-1,2,4-triazolylcarbo-thiohydrazides with ortho esters were studied. Except of the case of triethyl orthoacetate instead of the expected [1,2,4]triazolo[1,5-d][1,2,4,6]tetrazepin-5(7H)-thione ( 6 ) derivatives different rearranged products such as 7, 8, 21, 23, 25 , and 27 were obtained, derivatives 23 and 27 representing a novel ring system. Possible explanations were given for the formation of the rearranged products.     

Thiamorphinans. I

The present paper deals with the synthesis of 5,5a,6,7,8,9-hexahydro-5,9a-iminoethano-4H-naphtho[2,1-b] -thiophenes (I) as derivatives of the first of three novel isomeric S-heterocycles with morphinan-like structure (“thiamorphinans”).     

Study of alkaloids of the Siberian and Altai flora. 7. Synthesis of 18-amino-18-deoxy derivatives of elatidine

Reduction of elatidal oxime and imines based on methylamine, ethanolamine, tyramine, and S- and (±)-alaninols gave rise to the 18-amino-18-deoxy derivatives of elatidine.     

Benzimidazole condensed ring systems. 7. An entry to substituted 1h,6h-2,6a,10b-triazafluoranthene-1,3,6-(2h)-triones and related systems as possible chemotherapeutic agents

The syntheses of some derivatives of three new benzimidazole condensed ring systems; namely, 1H,6H-2,6a,10b-triazafluoranthene-1,3,6(2H)-trione ( 3 ), 1H,8H,11H-12-oxa-2,3a,7b-triazabenz[e]acephenanthrylene-1,3,8,11(2H)-tetrone ( 4 ) and 1H,4H-2,5,6a,10b-tetrazafluoranthene-1,3,4,6(2H,5H)-tetrone ( 10 ) are described. Two compounds exhibited in vitro antibacterial activity. Four compounds were screened for in vitro anti-HIV activity and three compounds were evaluated for antileukemic potency but were inactive.     

Pd-NHC catalyzed Suzuki–Miyaura couplings on 3-bromo-9H-pyrido[2,3-b]indole-6-sulfonamide

A series of novel α-carboline derivatives such as 3-aryl-9H-pyrido[2,3-b]indole-6-sulfonamides have been synthesized from the readily available low-cost raw material, benzotriazole which is subjected to nucleophilic aromatic substitution with 5-bromo-2-chloropyridine followed by sequential steps of cyclization, sulfonation, amidation, and finally Suzuki–Miyaura coupling reactions. The C–C bond formation between 3-bromo-9H-pyrido[2.3-b]indole-6-sulfonamide and various boronic acids was achieved with more accessible palladium pre-catalyst, Pd-PEPPSI-IPr via Suzuki coupling under microwave condition in a short reaction time with excellent yields.     

Diastereodivergent Synthesis of Hexahydro-6H-benzo[c]chromen-6-one Derivatives Catalyzed by Modularly Designed Organocatalysts

The diastereodivergent synthesis of hexahydro-6H-benzo[c]chromen-6-one derivatives with good to high diastereoselectivities (up to 98:2 d.r.) and enantioselectivities (up to >99 % ee) has been achieved by using a domino Michael/Michael/hemiacetalization reaction between trans-2-hydroxy-β-nitrostyrenes and trans-7-oxo-5-heptenals followed by oxidation. With use of appropriate modularly designed organocatalysts (MDOs) that are self-assembled in situ from amino acid derivatives and cinchona alkaloid derivatives, two different diastereomers of the desired hexahydro-6H-benzo[c]chromen-6-ones are obtained from the same substrates.