Proximity and the heteroatom effects on the carbon-13 chemical shifts of methyl-substituted phenols,anilines and thiophenols

Upfield substituent-induced ¹³C chemical shifts for aryl carbons of polymethyl substituted benzenes, phenols, anilines and thiophenols were investigated as a function of the proximity between substituents X and CH₃ (X = CH₃, NH₂, OH and SH). The results indicate that the induced shifts of the substituted aryl carbons are, in general, independent of the polar substituent but depend on the number of adjacent substituted aryl carbons. A ?2.0 ppm upfield shift was found for a substituted aryl carbon adjacent to one substituted aryl carbon and a ?3.8 ppm upfield shift for a substituted aryl carbon bound by two substituted aryl carbons. It is suggested that the near additivity of the upfield shifts is the result of changes in the bond order between the aromatic ring carbons in the region of the substituted aryl carbons due to distortion of the ring. The ¹³C chemical shifts of the methyl substituents for methyl substituted phenols, anilines and thiophenols were determined, and it was found that the values could be predicted from the additivity parameters reported for the analogous methylbenzenes plus an additional pair-interaction term associated with the through-space electronic influence of the heteroatom.     

Formation of Substituted Oxa‐ and Azarhodacyclobutanes

The preparation of substituted oxa‐ and azarhodacyclobutanes is reported. After exchange of ethylene with a variety of unsymmetrically and symmetrically substituted alkenes, the corresponding rhodium–olefin complexes were oxidized with H₂O₂ and PhINTs (Ts=p‐toluenesulfonyl) to yield the substituted oxa‐ and azarhodacyclobutanes, respectively. Oxarhodacyclobutanes could be prepared with excellent selectivity for incorporation of the oxygen atom on the more substituted carbon atom of the alkene. At the same time, azarhodacyclobutanes showed good‐to‐excellent selectivity for heteroatom incorporation on the less substituted carbon. Furthermore, it was shown that steric modifications of the ancillary ligand have a significant influence on the selectivity of Rh–olefin complex formation as well as formation of the substituted azametallacycles.     

Nitropyridines,their synthesis and reactions

Reaction of pyridine and substituted pyridines with N₂O₅ in an organic solvent gives the N‐nitropyridinium ion. When this is reacted with SO₂/HSO₃‐ in water, 3‐nitropyridine is obtained (77 % yield). With substituted pyridines the method gives good yields for 4‐substituted and moderate yields for 3‐substituted pyridines. The reaction mechanism is not an electrophilic aromatic substitution but one in which the nitro group migrates from the 1‐position to the 3‐position by a [1,5] sigmatropic shift. From 3‐nitropyridine, 5‐nitropyridine‐2‐sulfonic acid is formed in a two step reaction. From this, a series of 2‐substituted‐5‐nitropyridines has been synthesized. 3‐Nitropyridine and 4‐substituted‐3‐nitropyridines have been substituted with ammonia and amines by the vicarious nucleophilic substitution (VNS) method with ammonia and amines and by the oxidative substitution method in the position para to the nitro group. High regioselectivities and yields have been obtained in both cases to afford a series of 4‐substituted‐2‐alkylamino‐5‐nitropyridines. The VNS method has also been used in alkylation reactions with 3‐nitropyridines to form dichloromethyl‐and alkoxycarbomethyl‐β‐nitropyridines. From the appropriate substituted nitropyridines imidazopyridines and azaindoles have been formed.     

Spontaneous reactions of electron‐accepting substituted quinodimethane with substituted styrenes: Inductive and steric effects on the formation of a zwitterionic intermediate

Spontaneous reactions of an electron‐accepting substituted quinodimethane, 1‐(2,2‐dimethyl‐1,3‐dioxane‐4,6‐dione‐5‐ylidene)‐4‐(dicyanomethylene)‐2,5‐cyclohexadiene, with p‐substituted, α‐substituted, and β‐substituted styrenes were investigated. When p‐substituted styrenes were used as comonomers, no spontaneous reactions took place for styrenes with an electron‐accepting p substituent such as COOMe and CN groups, and both terpolymers and cycloadducts were formed for the other p‐substituted styrenes. When α‐substituted and β‐substituted styrenes were used as comonomers, no reactions occurred for α‐ and β‐substituted styrenes with a bulky phenyl group, and spontaneous reactions took place for those with a smaller methyl group. The reaction products were an alternating copolymer for α‐substituted styrene and both terpolymers and 5‐ethylidene‐2,5‐dimethyl‐1,3‐dioxane‐4,6‐dione for β‐substituted styrenes. The position of the methyl group in the styrenes significantly affected the product formation. This behavior in the spontaneous reactions was discussed on the basis of the ability of formation of the zwitterionic tetramethylene intermediate and its conformation, determined by polar and steric effects of the substituents in the substituted styrenes. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 5195–5206, 2005     

TeCl4 as a catalyst in cationic oligomerisations and polymerisations

TeCl₄ catalyses the oligomerisation and polymerisation of certain substituted phenylethylenes and substituted benzyl chlorides. The catalysis is cationic, TeCl₄ acting as a Lewis acid. The termination of polymerisation of the substituted ethylenes is by an internal Friedel-Crafts reaction, whereas that of the substituted benzyl chlorides is by reaction with chloride ions. Contrary to the usual reactivity sequence, stilbene was found to be more reactive than α-methylstyrene in the TeCl₄-catalysed polymerisations.     

Synthetic transformations of higher terpenoids: XXIX. Gold catalyzed cycloisomerization of propargylaminomethyl substituted and propargyloxymethyl substituted furanolabdanoids

16-Propargylaminomethyl substituted and 16-propargyloxymethyl substituted furanolabdanoids were synthesized, which under the action of AuCl₃ in acetonitrile underwent cycloisomerization forming 7-hydroxyisoindolines or 7-hydroxydihydroisobenzofurans substituted by a terpenoid fragment.     

N-(5-巯基-1,3,4-噻二唑-2-基)-N'-取代苯甲酰基脲与取代的苯氧乙酰基脲的合成与生物活性

通过2-氨基-5-巯基-1,3,4-噻二唑与取代苯甲酰基异氰酸酯及取代苯氧乙酰基异氰酸酯反应, 合成了21种新的取代苯甲酰基脲与取代苯氧乙酰基脲, 其结构用红外光谱、核磁共振氢谱和元素分析进行了确证, 初步的生物活性测定试验表明, 部分目标化合物具有良好的植物生长调节活性.     

Synthesis and Anticancer Activity Study of Some Novel Substituted and Fused Pyridotriazepine Derivatives

Various new substituted and fused pyridotriazepine analogues have been synthesized via different synthetic pathways. Among which are different heterocyclic compounds consisting of the pyridotriazepine backbone fused to different heterocyclic systems comprising either substituted pyrimidine nucleus such as compounds 3 – 9 or substituted 4‐aminopyridine nucleus such as compounds 10 – 16 . Besides, the tetrahydroquinoline derivative 17 , [1,2,4]triazolopyrimidine derivative 18 , thienodiazocine derivative 19 , dihydrobenzofuropyridine derivative 20 , and the substituted pyrrole derivative 21 were synthesized. In addition, different substituted pyridotriazepine derivatives as indicated in compounds 22 – 25 were designed and synthesized. Twenty‐five of the newly synthesized compounds were subjected to in vitro anticancer screening against mammalian colon carcinoma HCT‐116 cell line using Cisplatin as a reference drug. The anticancer activity screening results revealed that among the tested compounds, the tetrahydropyrido[1,2‐b]pyrimido[4,5‐e][1,2,4]triazepine derivative 4 substituted at C₂ and C₄ positions with S‐methyl and amino moieties, respectively, and the 2,4‐dithioxo analogue 9 and the 2‐thioxodipyrido[1,2‐b:2′,3′‐e][1,2,4]triazepine derivative 11 substituted at C₃ and C₄ with a cyano and amino moieties, respectively, exhibited moderate to strong anticancer activity against mammalian colon carcinoma HCT‐116 cell line.     

Synthesis and crystal structures of 2,3,12,13-tetraalkoxy-21,23-dithiaporphyrins and 2,3-dialkoxy-21-monothiaporphyrins

The tetraalkoxy and dialkoxy substituted 21,23-dithiaporphyrins and 21-monothiaporphyrins, respectively, having methoxy, butoxy, octyloxy and dodecyloxy substituents at β-thiophene carbons were synthesized and characterized. The X-ray structure was solved for tetrabutoxy substituted 21,23-dithiaporphyrin and it exhibited a more planar structure compared with unsubstituted S₂TPP, whereas the dimethoxy substituted 21-monothiaporphyrin showed a saddle shaped structure similar to unsubstituted STPPH.     

Substituted Tetraaza‐ and Hexaazahexacenes and their N,N′‐Dihydro Derivatives: Syntheses,Properties, and Structures

The palladium‐catalyzed coupling of a substituted o‐diaminoanthracene and a substituted o‐diaminophenazine to substituted 2,3‐dichloroquinoxalines furnishes 10 differently substituted N,N′‐dihydrotetraaza‐ or ‐hexaazahexacenes with the quinoxaline group of the azaacenes carrying fluorine, chlorine, or nitro groups. The N,N′‐dihydrotetraazahexacenes with hydrogen, chlorine, and fluorine subtituents are oxidized to azaacenes, whereas only the parent N,N′‐dihydrohexaazahexacenes, with hydrogen substituents, are oxidized by MnO₂. The resultant azaacenes are characterized by their optical and spectroscopic data. In addition, single‐crystal X‐ray structures have been obtained for the parent tetraazahexacenes and their difluoro‐substituted derivatives. The di‐ and tetrachloro derivatives of the N,N′‐dihydrohexaazahexacene have also been structurally characterized.     

Simple and convenient synthesis of tertiary benzanilides using dichlorotriphenylphosphorane

Various tertiary benzanilide derivatives were effectively synthesized from substituted benzoic acid and N-monoalkylated aniline using dichlorotriphenylphosphorane in chloroform. Yields were generally high, even when an electron-withdrawing group substituted the aromatic ring of aniline, or when an electron-donating group substituted the aromatic ring of benzoic acid. Allyl, Boc, MPM and the Z group were unaffected under these conditions.     

Synthesis of bromodifluoromethyl substituted pyrazoles and isoxazoles

Bromodifluoromethyl substituted β-diketone 3a-3d, prepared from corresponding ketones and ethyl bromodifluoroactate in the presence of sodium methoxide, reacted with aryl hydrazine derivatives affording bromodifluoromethyl substituted pyrazoles in high regioselectivity. The reaction of 3a-3d with hydroxylamine hydrochloride gave dihydroisoxazoles, which afforded bromodifluoromethyl substituted isoxazoles through dehydration by PPA or concentrated sulfuric acid.     

meso‐Ester and Carboxylic Acid Substituted BODIPYs with Far‐Red and Near‐Infrared Emission for Bioimaging Applications

A series of meso‐ester‐substituted BODIPY derivatives 1–6 are synthesized and characterized. In particular, dyes functionalized with oligo(ethylene glycol) ether styryl or naphthalene vinylene groups at the α positions of the BODIPY core ( 3 – 6 ) become partially soluble in water, and their absorptions and emissions are located in the far‐red or near‐infrared region. Three synthetic approaches are attempted to access the meso‐carboxylic acid (COOH)‐substituted BODIPYs 7 and 8 from the meso‐ester‐substituted BODIPYs. Two feasible synthetic routes are developed successfully, including one short route with only three steps. The meso‐COOH‐substituted BODIPY 7 is completely soluble in pure water, and its fluorescence maximum reaches around 650 nm with a fluorescence quantum yield of up to 15 %. Time‐dependent density functional theory calculations are conducted to understand the structure–optical properties relationship, and it is revealed that the Stokes shift is dependent mainly on the geometric change from the ground state to the first excited singlet state. Furthermore, cell staining tests demonstrate that the meso‐ester‐substituted BODIPYs ( 1 and 3 – 6 ) and one of the meso‐COOH‐substituted BODIPYs ( 8 ) are very membrane‐permeable. These features make these meso‐ester‐ and meso‐COOH‐substituted BODIPY dyes attractive for bioimaging and biolabeling applications in living cells.     

Synthesis of some thiazolyl and thiadiazolyl derivatives of substituted furan and pyrrole

Four series of substituted furan and pyrrole have been synthesized. The first series was prepared by cyclization of the key intermediates ethyl 5‐[(4‐substituted thiosemicarbazido)methyl]‐2‐methylfuran‐3‐carboxylates 2a‐2d and 1‐[(4‐acetyl‐5‐methyl‐1H‐pyrrol‐2‐yl)methylene]‐4‐substituted thiosemicarbazides 8a‐8d with chloroacetic acid or (ethyl bromoacetate) to afford the corresponding 4‐oxo‐3‐substituted thiazolidin‐2‐ylidene 3a‐3d or 3‐substituted thiazolidin‐4‐one 9a‐9d . On the other hand, heating of the intermediates 2a‐2d or 8a‐8d with acetic anhydride afforded the corresponding (N‐substituted acetylamino)‐2,3‐dihydro‐[1,3,4]thiadiazol‐2‐yl derivatives 4a‐4d and [1,3,4]thiadiazol‐2‐yl‐N‐substituted acetamide 10a‐10d respectively, while cyclization with p‐bromophenacyl bromide gave rise to the corresponding 3‐substituted thiazol‐2‐yl‐ylidene 5a‐5d and 11a‐11d respectively. Furthermore, 4‐oxo‐3‐substituted thioureido‐thiazolidin‐2‐yl 6a‐6d or 4‐oxo‐thiazolidin‐3‐yl‐3‐substituted thiourea 12a‐12d were obtained by reaction of the intermediates 2a‐2d or 8a‐8d with thioglycolic acid. Some of the synthesized compounds showed promising antimicrobial activities.     

Synthesis of Heterocyclic‐Substituted Novel Hydroxysteroids with Regioselective and Stereoselective Reactions

Polyhydroxy steroids bearing the 3β,5α,6β‐trihydroxy pattern were synthesized from different heterocyclic‐substituted unsaturated steroid by an easy and simple method with high yields. The endocyclic double bond of thiophene‐substituted and quinoline‐substituted steroids were converted to the trans‐diaxial diol by the regioselective and stereoselective reactions with m‐chloroperoxybenzoic acid in the basic medium.     

Synthesis and Antiproliferative Activity of Cyano and Amidino Substituted 2-Phenylbenzothiazoles

Series of cyano, dicyano, amidino, and diamidino substituted 2-phenylbenzothiazoles were prepared. Mono- and dicyano substituted benzothiazoles were obtained by condensation of appropriate substituted benzaldehydes with 2-aminothiophenol or 4-amino-3-mercaptobenzonitrile. The appropriate amidines or diamidines were prepared by Pinner reaction. The compounds were tested against breast, prostate, and lung cancer cell lines in a 72 h cytotoxicity assay. Many of the compounds had at 10 μM activity equivalent to 2-(4-aminophenyl)benzothiazole, while four compounds had significantly better activity, particularly in the breast cancer model.     

Hydrolysis of Cyclopropane Derivatives of Aspartic and Adipic Acids

Hydrolysis of substituted cyclopropane amino acids was performed. Free and partially substituted Z and E isomers of cyclopropane analogs of aspartic and adipic acids were obtained.     

Synthesis and Antiproliferative Activity of Cyano and Amidino Substituted 2-Phenylbenzothiazoles

Summary. Series of cyano, dicyano, amidino, and diamidino substituted 2-phenylbenzothiazoles were prepared. Mono- and dicyano substituted benzothiazoles were obtained by condensation of appropriate substituted benzaldehydes with 2-aminothiophenol or 4-amino-3-mercaptobenzonitrile. The appropriate amidines or diamidines were prepared by Pinner reaction. The compounds were tested against breast, prostate, and lung cancer cell lines in a 72 h cytotoxicity assay. Many of the compounds had at 10 μM activity equivalent to 2-(4-aminophenyl)benzothiazole, while four compounds had significantly better activity, particularly in the breast cancer model.     

Synthesis and some transformations of benzo-substituted 2-bromomethyl-4-methyl-2-chloro-2,3-dihydrofuro[3.2-c]-quinolines

A convenient synthetic procedure for substituted 2-bromomethyl-4-methyl-2-chloro-2,3-dihydrofuro[3.2-c]quinolines hydrobromides was developed, synthons for preparation of new substituted furoquinolines. Reactions with various nucleophiles were performed, and 2-(R’-methyl)-4-methyl-furo[3.2-c]quinolines substituted in the benzene ring were obtained.     

Pd(OAc)2-catalyzed orthogonal synthesis of 2-hydroxybenzoates and substituted cyclohexanones from acyclic unsaturated 1,3-carbonyl compounds

A Pd-catalyzed orthogonal synthesis of substituted 2-hydroxybenzoates and substituted cyclohexanones was developed for the first time. The substituted 2-hydroxybenzoates were obtained from acyclic unsaturated 1,3-carbonyl compounds using a combination of catalytic Pd(OAc)₂ and Cu(OAc)₂. On the other hand, the substituted cyclohexanones were produced from similar substrates via catalytic Pd(OAc)₂ and hydrogen chloride. Each transformation was clean, easy to work up, provided the desired compounds in good purities, and did not require column chromatography purification.