Facile Metal-Free Synthesis of 3-Aryl-4-Substituted Coumarins from O-Hydroxy Carbonyl Compounds

The intramolecular cyclization of the esters of salicylaldehyde, O-hydroxyacetophenones, methyl salicylate, and 2′-hydroxy chalcones by potassium hydroxide in pyridine leads to a short and convenient synthesis of 3,4-disubstituted coumarins. Twenty 3-phenyl coumarins were synthesized in 80–90% yields. No other by-product, such as 2-benzylchromone or β-diketones, was observed the reactions. The mild reaction condition involves the removal of more acidic benzylic proton, which leads to a relatively cheap, nontoxic, metal-free method for the synthesis of 3-aryl-4-substituted coumarins.     

Electrochemical Reduction of Mono- and Dihalothiophenes at Carbon Cathodes in Dimethylformamide. First Example of an Electrolytically Induced Halogen Dance

Cyclic voltammetry and controlled-potential electrolysis have been employed to probe the electrochemical reduction of a number of mono- and dihalothiophenes at carbon cathodes in dimethylformamide containing tetramethylammonium perchlorate. Reduction of 2-bromo-, 3-bromo-, 2-chloro-, 3-chloro-, and 2-iodothiophene gives rise to a single irreversible cyclic voltammetric wave for each compound that corresponds to the two-electron cleavage of the carbon-halogen bond, and thiophene is obtained as the only product. Cyclic voltammograms for the reduction of 2,3-dibromo-, 2,4-dibromo-, 2,5-dibromo-, 3,4-dibromo-, 2-bromo-5-chloro-, and 3-bromo-2-chlorothiophene each exhibit a pair of irreversible two-electron waves. Electrolyses of either 2,3-dibromo- or 2,4-dibromothiophene at potentials corresponding to the first voltammetric wave yield a two-to-one mixture of 3-bromo- and 3,4-dibromothiophene; under similar conditions, electrolyses of 2,5-dibromothiophene give a mixture of 2-bromo-, 3-bromo-, and 3,4-dibromothiophene, electrolyses of 2-bromo-5-chlorothiophene afford a mixture of 3-bromo-, 3,4-dibromo-, 3-bromo-2-chloro-, 4-bromo-2-chloro-, and 2-chlorothiophene, and electrolyses of 3-bromo-2-chlorothiophene yield 2-chlorothiophene. Aside from the last result, these product distributions appear to arise from an electrolytically induced halogen dance. When electrolyses of the dibromothiophenes and of 2-bromo-5-chloro- and 3-bromo-2-chlorothiophene are performed at potentials that correspond to the second voltammetric wave, thiophene is the only product obtained.     

Synthesis of 4-(thien-2-yl)-substituted coumarins through Lewis acid catalyzed Michael addition of thiophenes to 3-benzoylcoumarins followed by oxidation

3-Benzoyl-4-(thien-2-yl)coumarins have been obtained in good yields according to the S_N^H addition–oxidation protocol, involving the diastereoselective addition of thiophenes at C-4 of 3-benzoylcoumarins under BBr₃ catalysis, followed by oxidation of the intermediate 3,4-trans-3-benzoyl-4-(thien-2-yl)-3,4-dihydrocoumarins with DDQ. This two-step procedure can be regarded as nucleophilic substitution of hydrogen (S_N^H) on the heterocyclic ring of coumarins.     

Study of reaction of reformatsky reagent prepared from methyl bromocyclopentanecarboxylate and zinc with 2-oxochromen-and 6-bromo-2-oxochromen-3-carboxylic acids <Emphasis Type="Italic">N</Emphasis>-arylamides

Reformatsky reagent prepared from methyl 1-bromocyclopentanecarboxylate and zinc reacted with 2-oxochromen-and 6-bromo-2-oxochromen-3-carboxylic acids N-arylamides yielding 3-aryl-1,1-tetramethylene-and 3-aryl-9-bromo-1,1-tetramethylene-2,3,4,4a,5,10b-hexahydro-1H-chromeno[3,4-c]pyridine-2,4,5-triones as single diastereomers.     

Addition of Some Enamino Esters to 3-Substituted Coumarins

The addition of the enamino esters 1a, b to several coumarins with electron-withdrawing 3-substituents 2 yielded 3 and 4, whereas ethyl 3-amino-2-butenoate (1c) reacted surprisingly with its C-4 to give either an adduct 8 or pyrido [3,4-c] chromene 9.     

Synthesis and structure of 6-bromo-4-hydroxy-2,3-tetramethylene-3,4-dihydroquinazoline and its mixed crystal with 4-hydroxy-2,3-tetramethylene-3,4-dihydroquinazoline

Bromination of the alkaloid 2,3-tetramethylene-3,4-dihydroquinazoline by N-bromosuccinimide was studied. It was shown that either 4-hydroxy-2,3-tetramethylene-3,4-dihydroquinazoline or 6-bromo-4-hydroxy-2,3tetramethylene-3,4-dihydroquinazoline was formed depending on the ratio of reagents. Oxidation of 2,3tetramethylene-3,4-dihydroquinazoline by KMnO₄ produced 4-hydroxy-2,3-tetramethylene-3,4dihydroquinazoline. The crystal structures of 6-bromo-4-hydroxy-2,3-tetramethylene-3,4-dihydroquinazoline and its mixed crystal with 4-hydroxy-2,3-tetramethylene-3,4-dihydroquinazoline were studied by x-ray structure analysis. The enantiomeric molecules in all crystal structures formed associates owing to two opposing OH...N1 H-bonds.     

Preparation of cinnoline-3, 4-dicarbonitrile and -dicarboxylic acid

Attempts to prepare cinnoline-3,4-dicarboxylic acid from 3,4-dimethylcinnoline failed owing to the unreactivity of the 3-me group. Successive treatment of 3-bromo-4-chlorocinnolin with sodium toluene-p-sulphinate and potassium cyanide in dimethylformamide (DMF) gave 4-toluene-p-sulphonylcinnoline-3-carbonitrile and then cinnoline-3,4-dicarbonitrile (82%). Hydrolysis yielded cinnoline-3,4-dicarboxylic acid (53%). Cinnoline-3, 4-dicarbonitrile undergoes nucleophilic displacement of either the 4- or the 3-cyano group by ammonia or amine to give 4-amino- and 4-benzylaminocinnoline-3-carbonitrile but 3-dimethylamino-cinnoline-4-carbonitrile.     

4-Chloro-3-(trifluoroacetyl)- and 4-chloro-3-(methoxalyl)coumarins as novel and efficient building blocks for the regioselective synthesis of 3,4-fused coumarins

4-Chloro-3-(trifluoroacetyl)- and 4-chloro-3-(methoxalyl)coumarins react with electron-rich aminoheterocycles, dimethyl 1,3-acetonedicarboxylate, hydrazines, alkyl thioglycolates, and methyl sarcosinate to give a variety of 3,4-heteroannulated coumarins. The starting materials were prepared by the reaction of 4-hydroxycoumarin with trifluoroacetic anhydride and methyl 2-chloro-2-oxoacetate in the presence of trimethylsilylchloride. An NMR study and X-ray crystallographic analysis are reported.     

Synthesis of heterocycles based on arylation products of unsaturated compounds: XVII. Arylation of 2-acetylfuran and synthesis of 3-R-6-(5-aryl-2-furyl)-7<Emphasis Type="Italic">H</Emphasis>-[1,2,4]triazolo[3,4-<Emphasis Type="Italic">b</Emphasis>][1,3,4]thiadiazines

Reaction of 2-acetylfuran with arenediazonium chlorides under Meerwein reaction conditions led to the formation of 5-aryl-2-acetylfurans. The bromination of these compounds gave 2-bromo-1-(5-aryl-2-furyl)-ethanones that reacted with 4-amino-4H-5-R-1,2,4-triazole-3-thiols to form 3-R-6-(5-aryl-2-furyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines.     

Arylation of β-methallyl alcohol catalyzed by Pd(OAc)2 in combination with P(t-Bu)3: application to fragrance synthesis

Pd(OAc)₂ in combination with P(t-Bu)₃ catalyzes the coupling of β-methallyl alcohol with 1-bromo-3,4-(methylenedioxy)benzene (1a), 1-bromo-4-methoxybenzene (1b), or 1-bromo-4-tert-butylbenzene (1c). The reaction affords the corresponding 2-methyl-3-aryl-propanals, which are valuable floral fragrances. With 1a or 1b high reaction rates are obtained at 130 °C using NMP/water mixtures and an inorganic base such as Na₂CO₃. The chemoselectivity of the reaction is almost complete, so that the process appears practically feasible. In contrast, the coupling of β-methallyl alcohol with 1c proceeds with low reaction rates.     

Synthesis of 4-substituted azepino[3,4-b]indole-1,5-diones

Mono- or dibromo derivatives 2 and 3 were prepared by an efficient two-step route from 10-methyl-azepino[3,4-b]indole-1,5-dione 1. Elimination reaction on 2 gave access to 4-bromo-10-methyl-2H,10H-azepino[3,4-b]indole-1,5-diones 4. Finally, 4-substituted 10-methyl-2H,10H-azepino[3,4-b]indole-1,5-diones 6-14 were synthesised in good yields from 4 via palladium-mediated cross-coupling reactions.     

Efficient Solvent‐Free Synthesis of Benzothiazine‐Fused Pyrrolo[3,4‐c]coumarins: Cycloaddition Reactions between Coumarin‐Based Dihydrobenzothiazoles and Isocyanides

A new and unusual synthesis of benzothiazine‐fused pyrrolo[3,4‐c]coumarins, involving the ring‐opening of coumarin‐based dihydrobenzothiazoles and subsequent [4+1] cycloaddition reaction with isocyanides, was described. Thus, simple heating of various 3‐(2,3‐dihydro‐2‐methylbenzo[d]thiazol‐2‐yl)coumarins with isocyanides produced the title compounds in good yields under solvent‐free conditions.     

1,2-双[2-甲基-5-(3,4-二氟苯基)噻吩-3-基]全氟环戊烯的合成

在冰浴条件下, 2-甲基噻吩(1)与液溴反应生成3,5-二溴-2-甲基噻吩(2); 在－78 ℃条件下, 硼酸三丁酯加入2, 得到2-甲基-3-溴-5-硼酸基噻吩(3); 3,4-二氟溴苯与3反应得到2-甲基-3-溴-5-(3,4-二氟苯基)噻吩(4); 在－78 ℃下全氟环戊烯与4反应, 得到一种新的二芳基乙烯类光致变色化合物1,2-双[2-甲基-5-(3,4-二氟苯基)噻吩-3-基]全氟环戊烯(DT-1). 用IR, NMR, MS和元素分析确定了化合物DT-1的结构, 并对该化合物的光致变色特性进行了初步研究.     

10-Aryl-7,7-dimethyl-5,6,7,8,9,10-hexahydro-11H-pyrido[3,2-b][1,4]benzodiazepin-9-ones

In reactions of 3-(2-amino-3-pyridyl)amino-5,5-dimethylcyclohex-2-en-1-one with aromatic aldehydes (2- and 4-hydroxy-, 2-hydroxy-3-methoxy-, 4-dimethylamino-, 4-methoxy-, 2,4- and 3,4-dimethoxy-, 3,4-methylenedioxy-, 4-bromo-, 4-fluoro-, 4-chloro-, 2-nitro- and 3-nitrobenzaldehydes, furfural, and 2-thiophenecarbaldehyde), we have obtained the corresponding 10-aryl-7,7-dimethyl-5,6,7,8,9,10-hexahydro-11H-pyrido[3,2-b][1,4]benzodiazepin-9-ones.     

Multicomponent Synthesis of 2,5-Dioxo- and 4-Aryl-5-oxo-2-thioxo-1,2,3,4,5,6,7,8-octahydroquinazolines

Ten 2,5-dioxo- and 4-aryl-5-oxo-2-thioxo-1,2,3,4,5,6,7,8-octahydroquinazolines have been synthesized in three-component interactions of 1,3-cyclohexanedione or dimedone, urea or thiourea, and substituted benzaldehydes (3-bromo-, 4-bromo-, 4-fluoro-, 4-methoxy-, 3,4-methylenedioxy-, and 3-nitro-). 9-Aryl-4,5-dioxo-1,2,3,4,5,6,7,8-octahydro-9H-xanthenes were also formed in these reactions.     

Formation of the benzo[f]pyrazolo[3,4-c][1,2,5]-triazepine system in the template reaction of o-amino-o′-halophenylazopyrazoles

The substance isolated from the template cyclization of 4-(2-bromo-4-methyl-1-phenylazo)-5-amino-3-methyl-1-propylpyrazole was identified by spectroscopic methods as 5-(2-bromo-4-methylphenyl)-3,7-dimethyl-1-propyl-1,5-dihydrobenzo[f]-pyrazolo[3,4-c][1,2,5]triazepine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 802–804, June, 1979.     

Palladium-catalyzed C3-selective mono-arylation of 4-hydroxycoumarin

4-Hydroxycoumarin (1) is a useful synthon in synthetic organic chemistry and a basic skeleton of several bioactive compounds. The direct functionalization of 1 with novel catalytic system would provide an efficient meaning for construction of a chemical library. Here, we developed a new catalytic system using palladium(II) acetate for the C3 regioselective mono-arylation of 1. The 3-mono-arylated and the 3,4-disubstituted coumarins were synthesized to enable derivatization. This palladium-catalyzed direct arylation of 1 is effective for rapid diversification and chemical library construction.     

Condensed thiolane 1,1-dioxide systems. 2. Brominated cis-perhydrothieno[3,4-d]oxazoles and imidazoles

Bromocyclization of 2-bromo-4-ureido-2-thiolene 1,1-dioxide has given perhydrothieno[3,4-d]oxazol-2-imino 5,5-dioxide, in which hydrogen atoms are absent from one of the -methylene groups. In weakly basic media, this undergoes conversion into the corresponding aminooxazoline. Treatment of an aqueous solution of 2-bromo-4-ureido-2-thiolene 1,1-dioxide with bases gives a mixture of perhydrothieno[3,4-d]imidazol-2-one 5,5-dioxides in which the bromine atoms have the exo- and endo-orientations. In all the bicyclic compounds, the two rings are cis-fused.For Communication 1, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1264–1268, September, 1988.     

Zur Synthese sulfonierter Derivate von 2,3-Dimethylanilin und 3,4-Dimethylanilin

On the Synthesis of Sulfonated Derivatives of 2,3-Dimethylaniline and 3,4-Dimethylaniline Baking the hydrogensulfate salt of 2,3-dimethylaniline ( 1 ) or of 3,4-dimethylaniline ( 2 ) led to 4-amino-2,3-dimethylbenzenesulfonic acid ( 4 ) and 2-amino-4,5-dimethylbenzenesulfonic acid ( 5 ), respectively (Scheme 1). The sulfonic acid 5 was also obtained by treatment of 2 with sulfuric acid or by reaction of 2 with amidosulfuric acid. 3-Amino-4,5-dimethylbenzenesulfonic acid ( 3 ) and 5-Amino-2,3-dimethylbenzenesulfonic acid ( 6 ) were prepared by sulfonation of 1,2-dimethyl-3-nitrobenzene ( 9 ) to 3,4-dimethyl-5-nitrobenzenesulfonic acid ( 11 ) and of 1,2-dimethyl-4-nitrobenzene ( 10 ) to 2,3-dimethyl-5-nitrobenzenesulfonic acid ( 12 ), respectively, with subsequent Béchamp reduction (Scheme 1). Preparations of 2-amino-3,4-dimethylbenzenesulfonic acid ( 7 ) and of 6-amino-2,3-dimethylbenzenesulfonic acid ( 8 ) were achieved by the sulfur dioxide treatment of the diazonium chlorides derived from 3,4-dimethyl-2-nitroaniline ( 24 ) and from 2,3-dimethyl-6-nitroaniline ( 31 ) to 3,4-dimethyl-2-nitrobenzenesulfonyl chloride ( 29 ) and 2,3-dimethyl-6-nitrobenzenesulfonyl chloride ( 32 ), respectively, followed by hydrolysis to 3,4-dimethyl-2-nitrobenzenesulfonic acid ( 30 ) and 2,3-dimethyl-6-nitrobenzenesulfonic acid ( 33 ), and final reduction (Scheme 3). Compound 7 was also synthesized by reaction of 4-chloro-2,3-dimethylaniline ( 23 ) with amidosulfuric acid to 2-amino-5-chloro-3,4-dimethylbenzenesulfonic acid ( 20 ) and subsequent hydrogenolysis (Scheme 2). 4′-Bromo-2′, 3′-dimethyl-acetanilide ( 13 ) and 4′-chloro-2′, 3′-dimethyl-acetanilide ( 14 ) on treatment with oleum yielded 5-acetylamino-2-bromo-3,4-dimethylbenzenesulfonic acid ( 17 ) and 5-acetylamino-2-chloro-3,4-dimethylbenzenesulfonic acid ( 18 ), respectively. Their structures were proven by hydrolysis to 5-amino-2-bromo-3,4-dimethylbenzenesulfonic acid ( 21 ) and 5-amino-2-chloro-3,4-dimethylbenzenesulfonic acid ( 22 ), followed by reductive dehalogenation to 3 .     

Novel Copolymers of Styrene. 17. Ring-Trisubstituted Methyl 2-Cyano-3-Phenyl-2-Propenoates

Electrophilic trisubstituted ethylenes, ring-trisubstituted methyl 2-cyano-3-phenyl-2-propenoates, RPhCH = C(CN)CO₂CH₃ (where R is 2,4,6-trimethyl, 3,5-dimethoxy-4-hydroxy, 3,5-dimethyl-4-hydoxy, 3,4,5-trimethoxy, 2-bromo-3-hydroxy-4-methoxy, 5-bromo-2,3-dimethoxy, 5-bromo-2,4-dimethoxy, 6-bromo-3,4-dimethoxy were prepared and copolymerized with styrene. The monomers were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-trisubstituted benzaldehydes and methyl cyanoacetate, and characterized by CHN analysis, IR, ¹H and ¹³C-NMR. All the ethylenes were copolymerized with styrene (M₁) in solution with radical initiation (ABCN) at 70°C. The compositions of the copolymers were calculated from nitrogen analysis and the structures were analyzed by IR, ¹H and ¹³C-NMR. The order of relative reactivity (1/r₁) for the monomers is 5-bromo-2,3-dimethoxy (2.69) > 3,4,5-trimethoxy (1.86) > 6-bromo-3,4-dimethoxy (0.84) > 5-bromo-2,4-dimethoxy (0.39) > 4-hydoxy-3,5-dimethyl (0.31) = 2-bromo-3-hydroxy-4-methoxy (0.31) > 3,5-dimethoxy-4-hydroxy (0.24) > 2,4,6-trimethyl (0.22). Relatively high T_g of the copolymers in comparison with that of polystyrene indicates a decrease in chain mobility of the copolymer due to the high dipolar character of the trisubstituted ethylene monomer unit. Decomposition of the copolymers in nitrogen occurred in two steps, first in the 200–500ºC range with residue (1–6% wt), which then decomposed in the 500–800ºC range.