Furan derivatives. Part 10. Synthesis of cyclohepta[cd]benzofuran

Cyclohepta[cd]benzofuran 2 was synthesized by heating (5-oxo-5H-benzocyclohepten-4-yloxy)acetic acid 16 with sodium acetate in acetic anhydride or by photocyclization of 16 in acetonitrile. Several reactions of cyclohepta[cd]benzofuran 2 were examined. Protonation of 2 with trifluoroacetic acid occurred at the 2-position to give a tropylium ion 17 . Catalytic hydrogenation of 2 with palladium on charcoal proceeded smoothly to give tetrahydrocyclohepta[cd]benzofuran 18 . The Diels-Alder reaction of 2 with tetracyano-ethylene produced an adduct 19 . Formylation of 2 with phosphorus oxychloride and dimethylformamide occurred easily at the 2-position to afford compound 20 . Cyclohepta[cd]benzofuran 2 has both properties of heptafulvene and benzofuran.     

Chemical transformations of 3‐amino‐2‐quinolones

In order to find new antimalarial drugs, an exploration about the chemical properties of the starting compounds 3‐amino‐6‐chloro‐4‐phenyl‐1H‐quinolin‐2‐one ( 1 ) and 3‐amino‐4‐methyl‐1H‐quinolin‐2‐one ( 2 ) was developed. Acylation with acyl chloride, sulfonyl chloride and acetic anhydride were carried out. Despite a previous report [2], when acetyl chloride or acetic anhydride were assayed on 1 , only the diacetyl derivative 7 was obtained. When this compound was heated at reflux temperature in a mixture of acetic acid and acetic anhydride, it was transformed in the oxazoloquinoline 8 . Further reactions of the acyl derivatives with diazomethane afforded 1‐methylated compounds. Compound 2 gave the imine 16 by condensation with 4‐nitrobenzaldehyde.     

Synthesis of some new pyrimido[1,6-a]pyrimidines. Isolation of stable covalent hydrated pyrimido[1,6-a]pyrimidines

4-Amino-5-phenylpyrimidine 2 reacts with alkyl malonic acids 3 in acetic anhydride under reflux to give 2(4)H-pyrimido[1,6-a]pyrimidines 4. From these reactions some covalent hydrated pyrimido[1,6-a]pyrimidines 5 were also isolated, where the addition of the water molecule occurred to the 6,7 C = N bond. This covalent hydration is irreversible.     

Further studies on the reaction of N-(2-Hydroxyphenyl)anthranilic acids with acetic anhydride

Reaction of N-(2-hydroxyphenyi)anthranilic acids (I) with acetic anhydride was investigated further. Treatment of Ia with refluxing acetic anhydride for 3 hours afforded two minor products, IIIa and IV, in addition to the previously reported IIa. Under similar conditions, the reaction of Ib with acetic anhydride afforded IIb as reported previously, and IIIb and IXb in small quantities. Treatment of IIIb with hydrazine gave X, and treatment of IXb with methoxyethylamine gave XI. When Ic was allowed to react with refluxing acetic anhydride, there were obtained three minor products, IIIc, IXc and XIII, in addition to IIc. Reaction of Id with acetic anhydride gave IId, and two minor products IXc and XIV. The formation of these minor products in the reaction of Ia-d with acetic anhydride are discussed based on the reation mechanism proposed previously for the formation of II.     

Cidnp study of reactions of ketyls and dianions derived from benzophenone and fluorenone with acetic anhydride

A study is presented of ¹H and ¹³C CIDNP effects in the reactions of Na and Li salts of ketyls and dianions derived from benzophenone and fluorenone with acetic anhydride in tetrahydrofuran and dimethoxyethane. CIDNP effects were observed for products obtained by mixing of reactants both at high and at low field. Interpretation of the CIDNP effects (mixing at high field) indicates that in reactions of ketyls with acetic anhydride the primary step is O-acylation followed by spin-selective electron transfer between ketyl and O-acylated ketyl. At higher dilution or in the presence of strongly coordinating agents, heterolytic deprotonation of acetic anhydride by ketyl is also observed. CIDNP effects depend on the presence of ketyl which affects the relaxation of sterically accessible nuclei and also suppresses the intensity of ketone signals by rapid electron transfer. In reactions of dianions, electron transfer between dianion and acetic anhydride partly takes place, and the ketyl formed in this way reacts with a further molecule of acetic anhydride.     

Furan derivatives. Part 9. Synthesis and properties of cyclohepta[cd]benzofurans

Cyclohepta[cd]benzofurans 1a-c were synthesized by heating (5-oxo-5H-benzocyclohepten-4-yloxy)acetic acids 7a-c with sodium acetate in acetic anhydride or by irradiation of 7a-c in acetonitrile. Several reactions such as protonation, catalytic hydrogenation, Diels-Alder reaction, acylation, and photoreaction were examined for 1a-b . The results show that cyclohepta[cd]benzofurans have both properties of heptafulvene and benzofuran. The carbon-carbon double bond in the furan ring of 1a has aromatic character, however, the carbon-carbon double bonds in the seven-membered ring have olefinic character.     

Model studies on the kinetics and mechanism of polyarylate synthesis by acidolysis

Model reactions were carried out to simulate the acidolysis process for polyarylate synthesis by using p-tert-butylphenyl acetate (ptBuPhOAc) and benzoic acid in diphenyl ether. p-tert-Butylphenol was formed in the reaction mixture and its concentration stayed constant throughout the reaction. Acetic benzoic anhydride and benzoic anhydride were detected by NMR. Based on this experimental evidence, a mechanism for the acidolysis was proposed involving the mixed anhydride. The kinetics of the acidolysis reaction was studied for this model reaction. The overall reaction order is two and the reaction order with respect to each reactant is one. Second-order reaction rate constants were measured at different reaction conditions (200–250°C). The activation energy (E_a), activation enthalpy (ΔH^≠), and activation entropy (ΔS^≠) were calculated from these data. The thermodynamic parameters of the acidolysis reaction were also measured for the analogous reaction of p-tert-butylphenyl pivalate (ptBuPhOPiv) and benzoic acid. The kinetics of two other elementary reactions involved in the acidolysis reaction were also studied: p-tert-butylphenol with acetic anhydride or benzoic anhydride, and p-tert-butylphenyl pivalate with benzoic acid.     

α-pyrones. III Synthesis of 5,6-dihydro-1H-benzo[c]-quinolizin-1-ones from 6-(2-nitrostyryl)-2H-pyran-2-ones

The 6-(2-nitrostyryl)-2H-pyran-2-ones 1 were reduced with hydrogen over Pd/C at room temperature and atmospheric pressure giving the 2-benzoylamino-4-(1,2,3,4-tetrahydro-2-quinolinylidene-2-pentenedioic acid derivatives 2 which were converted, without isolation, into the 5,6-dihydro-1H-benzo[c]quinolizin-1-ones 4 in refluxing acetic anhydride. When α-aminoacids 2 were treated with acetic anhydride at room temperature oxazolones 3 were isolated, while by heating quinolizines 4 were found. Compounds 3 were transformed into 4 in refluxing acetic acid or anhydride.     

Kinetics and products of the reactions of ozone with toluene and its derivatives in acetic anhydride

The reactions of ozone with toluene and its derivatives in acetic anhydride were studied. It was found that competing parallel reactions of ozone with the aromatic ring and substituents occurred in the ozone-arene-acetic anhydride system. The ratio between these reaction paths depended on the arene structure and reaction conditions. The selectivity of the oxidation of toluene and its derivatives at the methyl group varied from 0 to 40%. The fraction of aromatic products decreased as the number of methyl groups at the ring was increased. Tri- and tetramethylbenzenes were oxidized only at the aromatic ring. The stability of an aromatic system increased upon the introduction of electron-acceptor substituents into the benzene ring. Aminotoluenes and hydroxytoluenes were oxidized with ozone mainly at the NH₂ and HO groups; however, as in the case of toluene, the aromatic ring and methyl group became the main directions upon their acylation. The oxidation of the methyl group in acetic anhydride in the presence of sulfuric acid was finished at the step of the formation of the acylated derivatives of benzyl alcohols and benzaldehydes, which are resistant to the action of ozone.     

Annelation of the thiazole ring to 1,2,4-triazines by tandem AN—AN or SN H—SN H reactions

The reactions of 3-aryl-1,2,4-triazines with aromatic thioamides and 4-arylthiosemicarbazides in acetic anhydride at room temperature afforded cyclic products of the tandem nucleophilic addition reactions, viz., tetrahydrothiazolo[4,5-e]-annelated 1,2,4-triazines, in good yields. The latter underwent aromatization in the presence of potassium permanganate.     

THE CONDENSATION REACTION OF BIS(PERFLUOROALKANESULFONYL)METHANES WITH AROMATIC ALDEHYDES

The ccndensation reactions occurred when heating bis(perfluoroalkane-sulfonyl)methanes with aromatic aldehydes in acetic acid anhydrideand gave high yields of 1-aryl-2,2-di(perfluoroalkanesulfonyl)ethylenesThe perfluoroalkanesulfonyl groups R_FSO_2 are known as the strongestelectron-attracting substituents~(1-2).This property is often used in theactivation of C-C multiple and 2,2'-C-H bonds.The synthesis and reactionsof perfluoroalkanesulfonyl substituted alkenes and alkynes are of greatinterest in synthetic organic chemistry~(3-6).Recently,Hanack~7 reported the preparation of 2-aryl-l-(perfluoroalkane-sulfonyl)acrylonitrile R_FSO_2C(CN)=CHAr.However,he failed to obtainthe 1,1-di(perfluoroalkanesulfonyl)alkenes by the Knoevenagel reactionof bis(perfluoroalkanesulfonyl)methane with aldehydes.     

Cyclization reactions of 3-hydrazino[1, 2, 4]triazino[5, 6-b]indole

The reaction of 3-hydrazino[1, 2, 4]triazino[5, 6-b]indole I with nitrous acid affords the azide III which could be cyclized with acetic anhydride to 10-acetyl-10H-tetrazolo[5′,1′:3, 4][1, 2, 4]triazino[5, 6-b]indole IIb . Cyclization reactions of I with acetic anhydride, ethyl chloroformate, carbon disulphide and aromatic aldehydes to the corresponding fused triazolo derivatives V–VIII are reported. On the other hand cyclization reactions of I with malononitrile, ethyl cyanoacetate, ethyl acetoacetate and acetylacetone to the corresponding condensed pyrazolino derivatives IX–XI are also reported. The reaction of I with α-dicarbonyl compounds to form mono and dihydrazones are reported. The structure of the compounds prepared and their cyclization mechanisms are reported.     

Preparation,proton and carbon-13 structure determination,and fungicidal activity of chlorinated 1-arylamino-1H-pyrrole-2,5-diones

1-(2′,4′-dichloro)phenylamino-1H-pyrrole-2,5-dione and 1-(2′,4′,6′-trichloro)phenylamino-1H-pyrrole-2,5-dione were prepared via direct chlorination of 2-phenyl-3-oxo-6-hydroxy-2H-pyridazine. Both pmr and mass spectroscopy clearly showed that dichloro substitution occurred in the aromatic moiety and not in the vinylic region of the molecule. The former method showed that pyridiazine- to pyrrole-ring isomerization had occurred already at the level of dichlorination. The identical 2′,4′-dichlorophenyl and 2′,4′,6′-trichlorophenylpyr-rolediones were also prepared by reaction of maleic anhydride with the appropriate arylhydrazine. Similar 2′,4-dichlorophenyl and 2′,4′,6′-trichlorophenyl analogues were prepared using dichloromaleic anhydride. Cmr spectroscopic techniques were used for pyridazine-/pyrrole-ring stereochemical assignment of products derived from dichloromaleic anhydride. 1-(2′,4′-dichloro)phenylamino-1H-pyrrole-2,5-dione and the trichloro-phenyl analogue were shown to exhibit fungicidal activity in both in-vivo and in-vitro assays.     

Synthesis of 6-mono- and 5,6-disubstituted 1,2,3-triazolo[4,5-d]pyrimidin-7-ones

The reactions of N-substituted 4-amino-3-benzyl-1,2,3-triazole-5-carboxamides with phosphorus oxochloride and dimethylformamide at 80 °C or with triethyl orthoacetate and acetic anhydride at 160 °C afforded 6-mono- or 5,6-disubstituted 1,2,3-triazolo[4.5-d]pyrimidin-7-ones in 30—85% and 65—90% yields, respectively.     

Reactions of the monoxides of 2,6-disubstituted pyrazines with phosphoryl chloride and acetic anhydride

The monoxides of 2, 6-dimethyl-( 1 ), 2, 6-diphenyl-( 2 ), and 2-methyl-6-phenylpyrazines ( 3 ) were subjected to the reactions with phosphoryl chloride and acetic anhydride. Some reactions of the chloropyrazines and hydroxypyrazines obtained thus were also investigated.     

Acid catalyzed chlorination of pyrrole with N-chloroacetanilide

The chlorination of pyrrole with N-chloroacetanilide was catalyzed by acetic acid. Transfer of Cl⁺ occurred directly to the α and β positions of pyrrole and a mixture of 2-chloro-, 3-chloro- and 2,5,-dichloropyrrole was formed. The α↗β ratio was 10:1 under competitive conditions.     

Syntheses and reactions of some 2,3-disubstituted pyrazine monoxides

The reactions of 2,3-dimethyl- ( 4 ), 2,3-diphenyl- ( 6 ), and 2-methyl-3-phenyl-pyrazine monoxides ( 8 and 9 ) with phosphoryl chloride and acetic anhydride resulted in giving monochloro- and monacetoxy-pyrazines in almost all cases. However, the reaction of 6 with acetic anhydride afforded exceptionally a diacetoxydihydro-pyrazine. These products were converted further to hydroxy or dichloro derivatives.     

Quino[1,2-c]quinazolines. II. Synthesis of 12,13-dihydro-11bH-quino-[1,2-c]quinazolines via the versatile intermediates 2-(2-amino-4,5-dimethoxyphenyl)-6,7-disubstituted-1,2,3,4-tetrahydroquinolines

The versatile intermediates 2-(2-amino-4,5-dimethoxyphenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroquinoline ( 2a ) and 6-(2-amino-4,5-dimethoxyphenyl)-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]quinoline ( 2b ) were used in the preparation of a wide variety of 12,13-dihydro-11bH-quino[1,2-c]quinazolines by reaction with triethyl orthoformate, cyanogen bromide, urea and carbon disulfide in pyridine. Reaction of the thio and keto products with methyl iodide and phosphorus oxychloride, respectively, gave the requisite methylthio and chloro derivatives. Novel Reissert type reactions occurred when the intermediates 2a,b were reacted with acetic anhydride or benzoyl chloride. The attempted dehydrogenation of 12,13-dihydro-2,3,9,10-tetramethoxy-11bH-quino[1,2-c]quinazoline ( 3a ) is also reported.     

Metal Triflate–Catalyzed Friedel–Crafts Acetylation of 3-Phenylsydnone

Friedel–Crafts acetylation at the 4-position of 3-phenylsydnone (1) was achieved via thermal heating overnight in moderate to good yields by employing various metal triflate catalysts (5–20 mol%), lithium perchlorate (0–20 mol%), and acetic anhydride (4 equivalents) using either acetonitrile or acetic anhydride, in excess, as solvent. Six commercially available, homogeneous metal triflate catalysts were investigated, and optimal conditions were determined. The best yields overall were achieved with indium triflate.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications ^® to view the free supplemental file.     

Reaction of 2-(phenylamino)benzoic and 2-(phenylamino)- and 2-methyl-6-phenylpyridine-3-carboxylic acid hydrazides with succininc anhydride

Reactions of 2-(phenylamino)benzoic and 2-(phenylamino)- and 2-methyl-6-phenylpyridine-3-carboxylic acid hydrazides with succinic anhydride in organic solvents at room temperature gave the corresponding 4-(2-aroylhydrazinyl)-4-oxobutanoic acids. The reactions in boiling acetic acid afforded N-(2,5-dioxopyrrolidin-1-yl)benzamide or N-(2,5-dioxopyrrolidin-1-yl)pyridine-3-carboxamide.