Synthesis of bis[2-methoxy-4-(11-oxo-7,8,9,10,11,12-hexahydrobenzo[a]acridin-12-yl)phenyl] succinates

Reactions of succinyl chloride with 4-hydroxy-3-methoxybenzaldehyde and 3-ethoxy-4-hydroxybenzaldehyde gave the corresponding succinates which were brought into the condensation with naphthalen-2-amine to obtain Schiff bases. The latter reacted with CH acids (cyclohexane-1,3-dione and 5,5-dimethylcyclohexane-1,3-dione) to form bis[2-alkoxy-4-(11-oxo-7,8,9,10,11,12-hexahydrobenzo[a]acridin-12-yl)phenyl]-succinates which can also be obtained by three-component heterocyclization of naphthalen-2-amine with bis-(2-alkoxy-4-formylphenyl)succinates and CH acid.     

Synthesis of <Emphasis Type="Italic">N</Emphasis>-[3-alkoxy-4-(hydroxy-, alkoxy-, or acyloxy)-benzylidene- and -phenylmethyl]biphenyl-2-amines

Condensation of aldehydes of the vanillin series (vanillin, vanillal, and ethers and esters derived therefrom) with biphenyl-2-amine in anhydrous methanol gave the corresponding Schiff bases which were reduced with Na[BH(OAc)₃] in benzene under mild conditions to obtain N-[3-alkoxy-4-(hydroxy-, alkoxy-, or acyloxy)phenylmethyl]biphenyl-2-amines.     

Synthesis and properties of (<Emphasis Type="Italic">E</Emphasis>)-4-[alkyl(aryl)iminomethyl]-2-methoxy(ethoxy)phenyl adamantane-1-carboxylates

Condensation of 4-formyl-2-methoxy(ethoxy)phenyl adamantane-1-carboxylates with aliphatic, cycloaliphatic, and aromatic amines gave the corresponding adamantane-containing Schiff bases as E isomers with respect to the CH=N azomethine bond. The reaction of 2-methoxy-4-(naphthalen-2-yliminomethyl)phenyl adamantane-1-carboxylate with cyclohexane-1,3-dione and dimedone led to the formation of 2-methoxy-4-(11-oxo-7,8,9,10,11,12-hexahydrobenzo[a]acridin-12-yl)phenyl adamantane-1-carboxylates. Quantum-chemical calculations of the energies of formation of E and Z isomers of some of the synthesized Schiff bases were performed.     

Reaction of 2′-hydroxy-1,1′: 3′,1″-terphenyl-5′-carbaldehyde with naphthalen-1-amine,quinolin-8-amine,and 1,3-diketones

Condensation of 2′-hydroxy-1,1′: 3′,1″-terphenyl-5′-carbaldehyde with naphthalen-1-amine and cyclohexane-1,3-dione, methyl 2,2-dimethyl-4,6-dioxocyclohexane-1-carboxylate, or dimedone gave the corresponding 7-(2′-hydroxy-1,1′: 3′,1″-terphenyl-5′-yl)-7,8,9,10,11,12-hexahydro-12H-benzo[c]acridin-8-ones. The reaction of 2′-hydroxy-1,1′: 3′,1″-terphenyl-5′-carbaldehyde with naphthalen-1-amine and indan-1,3-dione produced 7-(2′-hydroxy-1,1′: 3′,1″-terphenyl-5′-yl)-8H-benzo[h]indeno[1,2-b]quinolin-8-one. 7-(2′-Hydroxy-1,1′: 3′,1″-terphenyl-5′-yl)-7,8,9,10,11,12-hexahydrobenzo[b][1,10]phenanthrolin-8-ones were obtained by three-component condensation of 2′-hydroxy-1,1′: 3′,1″-terphenyl-5′-carbaldehyde with quinolin-8-amine and cyclohexane-1,3-dione, methyl 2,2-dimethyl-4,6-dioxocyclohexane-1-carboxylate, or dimedone.     

Dinuclear Schiff-base copper(II) complexes with various bridging groups

Three new centrosymmetric dinuclear copper(II) complexes, [Cu₂Cl₂(L¹)₂] (1), [Cu₂(μ _1,3-NCS)₂(L²)₂] (2), and [Cu₂(μ _1,1-N₃)₂(L³)₂] (3), where L¹, L², and L³ are the deprotonated forms of the Schiff bases 1-[(2-propylaminoethylimino)methyl]naphthalen-2-ol (HL¹), 1-[(3-methylaminopropylimino)methyl]naphthalen-2-ol (HL²), and 2-[(2-isopropylaminoethylimino)methyl]phenol (HL³), respectively, have been prepared and characterized by elemental analysis, IR spectra, and single-crystal X-ray crystallography. Each Cu is coordinated by the three donors of the Schiff bases and by two bridging groups, forming a square-pyramidal geometry.     

Green synthesis,electrochemical, and DFT studies on the corrosion inhibition of steel by some novel triazole Schiff base derivatives in hydrochloric acid solution

In this work, three triazole Schiff base derivatives 1-((1H-1,2,4-triazol-3-ylimino)methyl)naphthalen-2-ol (TMN), N-(furan-2-ylmethylene)-1H-1,2,4-triazol-3-amine (FTA) and N-(thiophen-2-ylmethylene)-1H-1,2,4-triazol-3-amine (TTA) were synthesized under ultrasonic irradiation and were investigated as corrosion inhibitors. FT-IR, NMR, and elemental analysis were used to elucidate the chemical structure of the synthesized inhibitors. The inhibitive characteristics of these inhibitors on C-steel corrosion in 1.0 M HCl were studied using three different techniques. The applied techniques were Electrochemical frequency modulation, electrochemical impedance spectroscopy, and potentiodynamic polarization curves. The acquired data from the experimental methods showed that the optimal concentration for TMN, FTA, and TTA is 1.0 × 10^?3 mol/L, and the inhibition efficiency reached up to 91.68%, 88.44%, and 87.29% for TMN, TTA, and FTA, respectively. Experiments also indicated that these compounds act as mixed-type inhibitors, and their concentration affects the inhibition efficiency in a directly proportional manner. Quantum paraments obtained from density functional theory (DFT) showed good agreement between experimental and computational results.     

Synthesis and serotonin antagonist and antianexity activities of pyrrolidine derivatives from 4-hydrazinyl-1-p-substituted phenyl-2,5-dihydro-1H-pyrrole-3-carbonitriles

Abstract   N-(p-substituted phenyl)-4-cyanopyrrolidin-3-ones and their corresponding hydrazines were prepared and used as starting materials to synthesize heterocyclic candidates as serotonin antagonist and antianexity agents. Condensation of hydrazines with selected aromatic aldehydes afforded the corresponding Schiff bases. The hydrazines were treated with phenyl isothiocyanate to afford the corresponding thiosemicarbazides, which were cyclized with ethyl bromoacetate to N-phenylthiazolidinones. The hydrazine was reacted with 1,2,4,5-tetrachlorophthalic anhydride to give the tetrachloroimide derivative. It was reacted with benzoyl acetonitrile, 2-(bismethylsulfanyl-methylene)malononitrile, 2-ethoxymethylenemalononitrile, or 2-cyano-3-ethoxyacrylic acid ethyl ester to afford the corresponding pyrazoline derivatives. Schiff bases were obtained by simple condensation of the hydrazine with different carbonyl compounds. All the compounds were screened for their serotonin antagonistic and antianexity activities, and they showed high activities compared to buspirone and diazepam as controls. Graphical abstract        

Synthesis of chiral benzoacridinone derivatives by three-component condensation of [(1<Emphasis Type="Italic">S</Emphasis>,4<Emphasis Type="Italic">S</Emphasis>)-1,7,7-trimethylbicyclo[2.2.1]hept-2-ylidene]acetaldehyde with naphthalen-1-amine and cyclic β-diketones

Three-component condensation of [(1S,4S)-1,7,7-trimethylbicyclo[2.2.1]hept-2-ylidene]acetaldehyde with naphthalen-1-amine and cyclic β-diketones gave 7-[(1S,4S)-1,7,7-trimethylbicyclo[2.2.1]hept-2-ylidenemethyl]-7,8,9,10,11,12-hexahydro-7H-benzo[c]acridin-8-one derivatives possessing three or more asymmetric carbon atoms. Steric factors were found to be responsible for the predominant formation of the (7R)-isomers (R/S ≈ 7: 5) and orientation of substituents in the cyclohexenone fragment. The same factors determined complete regioselectivity of the reaction with methyl 2,4-dioxocyclohexane-1-carboxylates as dicarbonyl component, which led to exclusive formation of methyl 8-oxobenzoacridine-11-carboxylates. In the reaction of [(1S,4S)-1,7,7-trimethylbicyclo[2.2.1]hept-2-ylidene]acetaldehyde with naphthalen-1-amine and barbituric acid as dicarbonyl component, the only product was that formed by two-component condensation of barbituric acid with bicyclic aldehyde.     

Synthesis of 12-hetaryl-9,9-dimethyl-7,8,9,10-tetrahydrobenzo[a]acridin-11(12H)-ones

Three-component condensation of naphthalen-2-amine with 5-arylfuran(thiophene, N-methylpyrrole)-2-carbaldehyde and 5,5-dimethylcyclohexane-1,3-dione, as well as condensation of N-[(5-arylfuran(thiophen)-2-ylmethylidene]naphthalen-2-amine with 5,5-dimethylcyclohexane-1,3-dione gave the corresponding 12-[5-arylfuran(thiophen, N-methylpyrrol)-2-yl]-7,8,9,10-tetradrobenzo[a]acridin-11(12H)-ones.     

Reaction of 2-dimethylaminomethylene-1,3-diones with dinucleophiles. X. synthesis of 5-substituted ethyl or methyl 4-isoxazolecarboxylates and methyl 4-(2,2-dimethyl-1-oxopropyl)-5-isoxazolecarboxylate

Reaction of ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates with hydroxylamine hydrochloride in methanol solution afforded in high yields the relative esters of 5-substituted 4-isoxazolecarboxylic acids II . These esters were hydrolyzed generally with concentrated hydrochloric acid-acetic acid mixtures to the corresponding carboxylic acids in satisfactory yields. Ethyl or methyl esters II isomerized with sodium ethoxide or methoxide, respectively, to the corresponding esters or hemiesters of 2-cyano-3-oxoalkanoic acids generally in excellent to satisfactory yields. Reaction of methyl 5,5-dimethyl-3-dimethylaminomethylene-2,4-dioxohexanoate with hydroxylamine hydrochloride afforded in moderate yield methyl 4-(2,2-dimethyl-1-oxopropyl)-5-isoxazolecarboxylate, which was converted by acid hydrolysis as above to 4-t-butyl-4-hydroxyfuro[3,4-d]isoxazol-6-(4H)-one.     

Hydrolysis study: Synthesis of novel styrenic Schiff bases derived from benzothiazole

Novel styrenic Schiff base derivatives of benzothiazole are synthesized. The condensation of 4-vinylbenzaldehyde 1 with either benzothiazol-2-amine or 4-methoxy-benzothiazol-2-amine leads to a mixture of two isomers. From 4-methyl-benzothiazol-2-amine and 6-fluoro-benzothiazol-2-amine, the N-(4-vinylbenzylidene)-4-methyl-benzothiazol-2-amine 8 and N-(4-vinylbenzylidene)-6-fluoro-benzothiazol-2-amine 9 are isolated, respectively. The structures of the synthesized Schiff bases are confirmed through a combination of various spectroscopic techniques including IR, UV, ¹H and ¹³C NMR. A kinetic study of the hydrolysis process of derivatives 6 and 9 in buffered aqueous medium at pH 4.4, 7.4 and 8.5 is conducted by UV spectroscopy. It is shown that the hydrolysis of these compounds is a first order reaction showing an increasing rate as the medium acidity is enhanced.     

Synthesis of new benzo[<Emphasis Type="Italic">c</Emphasis>]phenanthridine derivatives

Three-component condensation of naphthalen-1-amine with triethyl orthoformate and dimedone or cyclopentane-1,3-dione, as well as the reaction of naphthalen-1-amine with 2-acetyl-5,5-dimethylcyclohexane-1,3-dione, gave the corresponding 2-[1-(α-naphthylamino)alkylidene]cycloalkane-1,3-diones which underwent intramolecular cyclization to 7,8,9,10-tetrahydrobenzo[c]phenanthridin-7-one derivatives on heating in polyphosphoric acid. 9,9-Dimethyl-7,8,9,10-tetrahydrobenzo[c]phenanthridin-7-one was reduced to 9,9-dimethyl-7,8,9,10-tetrahydrobenzo[c]phenanthridin-7-ol with sodium tetrahydridoborate.     

Synthesis of N-arylsulfonyl-2-aryl(hetaryl)aminoacetic acids

Hydrolytic transformations of 4-[2,2,2-trichloro-1-(arylsulfonylamino)-and-(ethoxycarbonylamino)ethyl]phenyloxy(or sulfanyl)acetic acids under microwave irradiation in alkaline medium involve both trichloromethyl group and ester fragment to give N-arylsulfonyl-2-[4-carboxymethyloxy(or sulfanyl)phenyl]-2-aminoacetic acids in good yields. Hydrolysis of methyl 4-[2,2,2-trichloro-1-(arylsulfonylamino)ethyl]phenyloxy(or sulfanyl)acetates without microwave activation occurs only at the ester group with quantitative formation of 4-[2,2,2-trichloro-1-(arylsulfonylamino)ethyl]phenyloxy(or sulfanyl) acetic acids. N-[2,2,2-Trichloro-1-(1-naphthyl, 2-furyl, and 1-methylindol-3-yl)ethyl]-4-chlorobenzenesulfonamides in alkaline medium under microwave irradiation were converted in 10–15 min into the corresponding N-(4-chlorophenylsulfonyl)-2-aryl-2-aminoacetic acids in preparative yields.     

Synthesis of α-amino acids using transition metal catalysis - alkylation of schiff bases derived from α-amimo acid esters (regio,stereo - selectivity)

A general approach to the synthesis of γ,δ-unsaturated α-amino acid esters is described. Schiff bases derived from glycine and alanine esters were alkylated in the presence of palladium or molybdenum catalysts under neutral or basic conditions using allylic carbonates, esters or halides, (20–95% yield). These less stabilized nucleophiles reacted with the η³ allyl species on the side opposite to the palladium and they can be classified as soft nucleophiles. The regioselectivity was studied with various unsymmetrical electrophiles. After hydrolysis, several functionalized α-amino acids of biological interest (enzymes inhibitors) were obtained. Asymmetric palladium allylic alkylation of the benzophenone imine glycine methyl ester using Pd(OAc)₂ + (+)DIOP was achieved with up to 68 % ee ; the enantioselective Pd-promoted alkylation of this new and useful prochiral nucleophile for the synthesis of α-amino acids is one of the highest ee known.     

Some chemical transformations of alkyl (4-aminophenyl)carbamates

Azo coupling of diazonium salts derived from alkyl (4-aminophenyl)carbamates with ethyl α-methylacetoacetate gave ethyl 5-alkoxycarbonylamino-1H-indole-2-carboxylates. The condensation of aminophenylcarbamates with aromatic aldehydes in ethanol afforded the corresponding Schiff bases. Cyclohexyl {4-[(4-methoxyphenyl)methylidene]aminophenyl}carbamate reacted with chloroacetyl chloride in dioxane in the presence of triethylamine to produce cyclohexyl {4-[3-chloro-2-(4-methoxyphenyl)-4-oxoazetidin-1-yl]phenylcarbamate, and the reaction of benzyl {4-[(4-nitrophenyl)methylidene]aminophenyl}carbamate with sulfanylacetic acid in DMF led to the formation of benzyl {4-[2-(4-nitrophenyl)-4-oxo-1,3-thiazolidin-3-yl]-phenyl}carbamate.     

Efficient Synthesis of Substances Related to Cinacalcet Hydrochloride via Heck Coupling

Efficient synthetic methods to process substances related to cinacalcet hydrochloride 1, generated during the preparation, were described. The compounds were identified as [1-(7,8-dihydro-naphthalen-1-yl)-ethyl]-[3-(3-trifluoromethyl-phenyl)-propyl]-amine hydrochloride 2,[1-(5,6,7,8-tetrahydro-naphthalen-1-yl)-ethyl]-[3-(3-trifluoromethyl-phenyl)-propyl]-amine hydrochloride 3 and [1-(naphthalen-2-yl)-ethyl]-[3-(3-trifluoromethyl-phenyl)-propyl]-amine hydrochloride 4. All were prepared from commercially available materials in several linear steps and characterized by their respective spectral data.     

Copper(II) Complexes with Asymmetrical Schiff Base Ligands Derived from 2‐Acetylpyrazine

New copper(II) complexes of asymmetrical tetradentate Schiff bases containing pyrazine have been prepared and thoroughly characterised by elemental analysis, IR and electronic spectroscopy, mass spectrometry and magnetic measurements. Two alternative methods were used in the isolation of the complexes: template synthesis in the preparation of Cu(SalDpyz)ClO₄ (HSalDPyz = derived from the condensation of salicylaldehyde, acetylpyrazine and 1,2‐ethylendiamine, 2‐methyl‐1,2‐propylendiamine, 1,2‐phenylendiamine) and direct interaction between copper perchlorate and the corresponding Schiff base, as in the isolation of Cu(AEPyz)(ClO₄) (HAEPyz = (Z)‐4‐[2‐{[2‐{[(E)‐1‐(pyrazinyl)ethylidene]amino} ethyl)amino]‐3‐penten‐2‐one)]. [Cu(SalEn)(py)(OClO₃)][Cu(SalEn)(py)]ClO₄ ( 1 ) (SalEn = 4‐(2‐hydroxyphenyl)‐3‐aza‐3‐buten‐1‐amino, py = pyridine), metal precursor in the preparation of Cu(SalEnpyz)(ClO₄) (HSalEnpyz = 2‐{E(2‐{[(E)‐1‐(2‐pyrazinyl)ethylidene]amino}ethyl)imino]methyl}phenol), was crystallographically characterised. The crystal structure of [Cu(AEpyz)]ClO₄ ( 2 ) is also reported.     

Novel approach to the synthesis of 3-acyl substituted indolizines. The synthesis of 3-(indolizinyl-2)alanine and 4-(indolizinyl-3) homoalanine derivatives

A novel approach to the synthesis of 3-acylindolizines and the transformations of some acids into tryptophane analogues are described. Reaction of ethyl 2-pyridinylacetate and methyl 2-quinolinylacetate with N-trifluoroacetyl-5-bromo-4-oxonorvaline methylester led to N-trifluoroacetyl-3-(1-ethoxycarbonylindolizinyl-2) alanine methyl ester and N-trifluoroacetyl-3-(3-methoxycarbonylpyrrolo [1,2-a]quinolinyl-2) alanine methyl ester, respectively. Treatment of ethyl 2-pyridinylacetate and 2-pyridinylacetonitrile, first with N,N-dimethylformamide dimethyl acetal (DMFDMA), followed by reaction with phenacyl bromide, gave the corresponding 3-benzoylindolizines, while the reaction of ethyl 2-pyridinylacetate and 2-pyridinylacetonitrile with DMFDMA, followed by treatment with (S)-N-trifluoroacetyl-5-bromo-4-oxonorvaline methyl ester, gave the corresponding N-trifluoroacetyl-4-oxo-4-(indolizinyl-3)homoalanine methyl esters.     

Schiff碱型双冠醚的合成及性质

用脂链或芳环桥联两个苯并—15—冠—5单元的双冠醚报道较多,而桥联苯并-18-冠-6或苯并-12-冠-4单元的双冠醚报道较少。本文报道以α,ω-二卤代烷或二(对甲苯磺酸)二甘醇酯与邻羟基苯甲醛反应,制成相应的二醛化合物1_(α-∫)后使它们分别与4′-氨基苯并-18-冠-6或4′-氨基苯并-12-冠-4反应,得到脂芳混合桥联的schiff碱型双冠醚2_(b-∫)或3_(?)。     

Synthesis and some transformations of 4-aryl-substituted amines of the tetrahydropyran series

The reaction of 2-isopropyltetrahydropyran-4-one [obtained by isomerization and hydration of 3-isopropylpent-1-en-4-yn-3-ol in the presence of 5% sulfuric acid and mercury(II) sulfate] with ethyl cyanoacetate gave ethyl cyano(2-isopropyltetrahydropyran-4-ylidene)acetate which was treated with 4-tolylmagnesium chloride. The resulting ethyl cyano[2-isopropyl-4-(4-tolyl)tetrahydropyran-4-yl]acetate was subjected to decarbethoxylation to obtain 2-isopropyl-4-(4-tolyl)tetrahydropyran-4-ylacetonitrile. The latter was reduced to the corresponding amine with lithium tetrahydridoaluminate, and the reduction product was brought into condensation with aromatic aldehydes. The Schiff bases thus formed were reduced with sodium tetrahydridoborate, followed by N-acylation with acetyl and propionyl chlorides.