Tandem Parham cyclisation--α-amidoalkylation reaction in the synthesis of the isoindolo[1,2-a]isoquinoline skeleton of nuevamine-type alkaloids

C-12b substituted isoindolo[1,2-a]isoquinolones 4 are prepared efficiently via a tandem Parham cyclisation--α-amidoalkylation reaction. Thus, Parham cyclisation on imide 1 generates a 12b-hydroxy isoindolo[1,2-a]isoquinolone, which is an immediate precursor of an N-acyliminium ion. Intermolecular alkylation with different π-nucleophiles (allyl silanes or enol ethers) is accomplished upon treatment with Lewis acids (BF₃·OEt₂, TiCl₄) to obtain nuevamine-type derivatives in high yields (69-95%) under mild conditions.     

Modification of the Pictet–Spengler reaction in the synthesis of fused 2,3-benzodiazocines

A new strategy for the synthesis of the eight-membered heterocyclic skeleton of tetrahydro-quinazolino[3,2-c][2,3]benzodiazocin-15-ones, based on the Pictet–Spengler reaction of 3-amino-2-[2-(3,4-dimethoxyphenyl)ethyl]quinazolin-4(3H)-one with carbonyl compounds in acidic media, is proposed.     

Effects of substituent and catalyst on the intramolecular Povarov reaction—synthesis of chromenonaphthyridines

2-(N-Alkenyl-N-aryl)aminochromone-3-carbaldehyde undergoes intramolecular Povarov reaction with aromatic amines in the presence of Ph₃P·HClO₄ to produce chromenonaphthyridine. The effects of substituent and catalyst have been studied. The substituent on the alkenyl part of aminochromone controls the mode of reaction as well as the stereochemistry of the product.     

Combination of the Claisen-Schmidt reaction,the Michael addition,and the Hantzsch reaction in the synthesis of 2,6′-bis-aryl-3,4′-bipyridines

Russian Chemical Bulletin - Pyridine-3-carbaldehyde reacted with 1-(aryl)ethan-1-ones to give 1,5-diaryl-3-(pyridin-3-yl)pentane-1,5-diones, which were further converted to...     

Enantioselectivity of the reaction of α-amino acids with sodium azide and triethyl orthoformate in the synthesis of tetrazoles

Russian Journal of Organic Chemistry -     

Hydroformylation of olefins produced in the Fischer—Tropsch synthesis

Russian Chemical Bulletin - Alcohols were obtained by the one-stage hydroformylation of olefins from the hydrocarbon fraction C6–C9, which was produced in the Fischer—Tropsch synthesis...     

The Wittig–Horner reaction for the synthesis of neratinib

The Wittig–Horner reaction is a classic method to get alkenes by reaction phosphonates with carbonyl compounds. In this study, it was used for the synthesis of the anticancer drug neratinib. In this method, ethyl diethoxyphosphinylacetate and dimethylaminoacetaldehyde diethylacetal, replacing (E)-4-(dimethylamino)but-2-enoyl acid hydrochloride and oxalyl chloride, were used to synthesize the 6-position side chain of neratinib.     

Three-component one-pot reaction for the synthesis of β-amide ketones

β-amide ketones were synthesised by a three-component one-pot reaction of phenylacetylene, aldehydes, and amides in anhydrous acetonitrile containing trifluoroacetic acid and acetic acid in the presence of AlCl₃ catalyst. The title compound structures were identified by ¹H NMR, ¹³C NMR, MS, and elemental analysis.     

Application of the Thorpe—Ziegler reaction for the synthesis of functionalized thiophenes,thienopyrimidines, and thienotriazines

Approaches to the synthesis of 3-aminothiophene-2,4-dicarboxylic acid derivatives and to their conversions into thieno[3,4-d]pyrimidines, thieno[3,4-d]-1,2,3-triazines, and thieno[3,2-d]pyrimidines are developed.     

Investigation of regioselectivity in the synthesis of spiro [pyrrolidine-2,3′-oxindoles] by use of the Huisgen reaction

The Huisgen reaction has been used to synthesize five-membered heterocyclic compounds in high yield and with high regio and stereoselectivity. In the synthesis of spiro [pyrrolidine-2,3′-oxindole] derivatives from isatin, α-amino acids, and (E)-β-phenyl nitroolefins, two regioisomers were obtained in each reaction. The regioselectivity of the major product was found to be different from that in reported work, and was investigated at the B3LYP/6-311G* level of theory. On the basis of this new finding, several conditions, for example molar ratio, solvent, and temperature, which affect the regioselectivity of this reaction were investigated; the results obtained are discussed. It was found that the regioselectivity of this reaction was affected by solvent and temperature, irrespective of the ratio of the reactants. Low temperature and high solvent polarity leads to high regioselectivity, and protic solvents result in higher yield and regioselectivity. These results are of benefit for regioselective synthesis of some compounds.     

Application of charge transfer reaction in the pharmaceutical analysis——Determination of chlorhexidine acetate

A spectrophotometric method for the determination of chlorhexidine acetate is described. The reaction between chlorhexidine acetate and chloranil took place in an alcohol-acetone solution at room temperature. The composition of the charge transfer complex is 1:2. Beer's law is obeyed in the concentration range of 15--270 μg·mL-1 with correlation coefficient 0.9995. The apparent molar absorptivity is 2.21×103 L·mol-1·cm-1 at 412 nm. The method is accurate (with a recovery of 100±1.6%) and precise (RSD=1.0%). It was successfully applied to determine chlorhexidine acetate in suppository or disinfectant solution.     

Enantioselective intramolecular α-amidoalkylation reaction in the synthesis of pyrrolo[2,1-a]isoquinolines

BINOL-derived chiral Brønsted acids are capable of carrying out the intramolecular α-amidoalkylation of a tertiary N-acyliminium ions when a methoxylated benzene ring is used as internal π nucleophile. The reaction can be applied to the synthesis of pyrrolo[2,1-a]isoquinolines and use of the sterically congested acid 3e is determinant to obtain good levels of enantioselection.     

Tandem one-pot synthesis of α-(aminomethylene)-γ-butyrolactones via regioselective epoxide ring-opening with the Blaise reaction intermediate

A novel tandem one-pot method for the synthesis of α-aminomethylene-γ-butyrolactone derivatives has been developed through the regioselective epoxide opening reactions with the Blaise reaction intermediates, generated by the reaction of a Reformatsky reagent with nitriles. Formation of a modified Blaise reaction intermediate by the addition of a stoichiometric amount of n-BuLi followed by slow addition of epoxide is required for the good yield of γ-butyrolactones.     

Unexpected Z-stereoselectivity in the Ramberg-Bäcklund reaction of diarylsulfones leading to cis-stilbenes: the effect of aryl substituents and application in the synthesis of the integrastatin nucleus

With certain substituent patterns, benzyl benzyl sulfone systems have been found to give unexpectedly high Z-stereoselectivity (up to E:Z = 1:16) in the Meyers variant of the Ramberg-B?cklund reaction. A range of sulfones, bearing various aryl substituents, were explored to rationalize this unprecedented selectivity for Z-stilbene systems. This high level of double bond stereocontrol has also been utilized in the synthesis of integrastatin nucleus, the core of two highly bioactive anti-HIV compounds.     

A practical and efficient green synthesis of β-aminophosphoryl compounds via the aza-Michael reaction in water

Biphasic systems room temperature imidazolium ionic liquid (RTIL)/water or water as a solvent significantly accelerate the addition of amines to vinylphosphoryl compounds hence opening green and effective synthesis of β-aminophosphoryl compounds in excellent yields over short reaction times. The application of water, being the cheapest and most non-toxic solvent, without any catalyst or co-solvent, is more advantageous as it provides a simple isolation procedure for products having high purity (> 95% according to the NMR data) via simple freeze-drying and does not require extraction with organic solvents. The solubility of the starting phosphorus substrate in water does not play crucial role in the reaction as it was demonstrated using water insoluble diphenylvinylphosphine oxide. In contrast to typical procedures, using a reactant ratio (vinylphosphoryl compound: amine) of 2:1 readily resulted in double phosphorylation of primary amines, including polyamines, in water.     

Tandem synthesis of [1,2,4]-triazoles mediated by iodine—a regioselective approach

A tandem regioselective one-pot synthesis of 3-amino-[1,2,4]-triazoles has been achieved from 1,3-disubstituted thioureas using molecular iodine. In this one-pot strategy, the intermediate carbodiimide generated in situ from thiourea upon reaction with HCONHNH₂ gives diaryl/alkylhydrazinecarboximidamide or acylureidrazone, which then undergoes an intramolecular cyclodehydration to afford the corresponding 3-amino-[1,2,4]-triazole. The product regioselectivity for unsymmetrical 1,3-disubstituted thioureas correlate well with the pK_as of the parent amines attached, in which the amine having higher pK_a goes to the ring nitrogen while the other nitrogen remains flanked as an exocyclic nitrogen of the triazole core. This method is milder and environmentally sustainable giving good to excellent yields of the desired products.     

Efficient synthesis of 3-arylbutadiene sulfones using the Heck–Matsuda reaction

An efficient and practical method for a scalable synthesis of 3-arylbutadiene sulfones deals with the ligand-free Heck–Matsuda reaction of sulfolene with aryldiazonium tetrafluoroborates followed by triethylamine-promoted double bond shift.     

Generation of sulfur ylides by the desilylation of α-trimethylsilylbenzyl sulfonium salts

The [2,3]-sigmatropic rearrangement of sulfur ylides derived via the desilylation of several α-trimethylsilylbenzyl sulfonium salts has been studied. The initially formed ylide was found to rapidly equilibrate with the thermodynamically more stable ylide. In the absence of trapping reagents, a Sommelet-Hauser type rearrangement occurs.     

Knoevenagel reaction in [MMIm][MSO₄]: synthesis of coumarins

The ionic liquid 1,3-dimethylimidazolium methyl sulfate, [MMIm][MSO?], together with a small amount of water (the amount taken up by the ionic liquid upon exposure to air), acts efficiently as both solvent and catalyst of the Knoevenagel condensation reactions of malononitrile with 4-substituted benzaldehydes, without the need for any other solvent or promoter, affording yields of 92%-99% within 2-7 min at room temperature. When L-proline is used as an additional promoter to obtain coumarins from o-hydroxybenzaldehydes, the reaction also proceeds in high yields. Work-up is very simple and the ionic liquid can be reused several times. Some of the coumarins obtained are described for the first time.     

Tandem A N—A N reactions in the synthesis of 1H-pyrrolo[3,2-e]-1,2,4-triazines and products of their oxidative transformations

The reactions of 3-aryl-1,2,4-triazines with -aminovinyl ketones or ethyl -aminocrotonates in acetic anhydride at room temperature afforded cyclic products of the tandem nucleophilic addition, viz., 3a,4,7,7a-tetrahydro-1H-pyrrolo[3,2-e]-1,2,4-triazines, in good yields. Under oxidative conditions, the latter compounds underwent the pyrrole-ring opening under the action of potassium permanganate to form the corresponding triazinones and were transformed into thriazolyl-substituted pyridines under the action of selenious acid.