Regioselective formylation of 1,3-disubstituted benzenes through in situ lithiation

A facile method of regioselective formylation of disubstituted benzene via in situ deprotonation/metalation using n-BuLi/TMEDA/DIPA has been developed. Effect of different electron withdrawing and electron donating substituents in 1,3-interrelated aromatic system was studied; the metalation mostly occurred at the 2-position to afford the desired products in high yields.     

An expedient synthesis of cis/trans-1,3-disubstituted cyclobutanols

A two-step procedure is described to access 3-alkoxycyclobutanones from chloroacetyl chloride utilizing a step-wise [2+2] ketene cycloaddition followed by catalytic hydrogenation to reduce the α-chlorine in a single reaction sequence. The resulting cyclobutanones can be readily converted into a variety of cis or trans-1,3-disubstituted aminocyclobutanols and cyclobutanediols.     

Cu(I)-catalyzed one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles via nucleophilic displacement and 1,3-dipolar cycloaddition

An efficient method is described for the regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles in high yields from a variety of Baylis-Hillman acetates and terminal alkynes with sodium azide using CuI as a catalyst, in either water or polyethylene glycol (PEG). This procedure is operationally simple and environmentally benign. Polyethylene glycol (PEG) serves as an efficient reusable solvent with higher efficiency.     

Out-of-plane deformation of the azulene ring in crystal structures of simply substituted azulene derivatives

The crystal structures of 1,3-bis(4-bromophenyl)- and 1,3-di(2-thienyl)azulenes (5 and 6) were elucidated by X-ray analysis. Two aryl groups connect to the azulenyl core with dihedral angles of 34.9-41.6° and the two aryl planes of the groups slant against the azulene ring toward different ways in their crystal structures. It was also found that the azulene rings of 5 and 6 showed a slight out-of-plane deformation in the way that the hydrogen atoms at the 4- and 8-positions are apart from the neighboring aryl ortho-hydrogen atoms to fill in the vacant space made by the slanting aryl planes.     

The furan approach to oxacycles: synthesis of medium-size 2,3-disubstituted oxacycles

We describe an efficient new approach for the synthesis of medium-size oxacycles that is based on the oxidation of a furan ring with singlet oxygen followed by an intramolecular Michael addition. This present study enlarges the scope of the furan approach strategy for the synthesis of oxepanes.     

Electron ionization and methane chemical ionization mass spectrometry study of some 2,2-disubstituted 1,3-dioxolanes, 1,3-dithiolanes, 1,3-oxathiolanes and 1,3-dioxanes. Gas-phase lactone and thiolactone formation

The electron ionization and methane chemical ionization mass spectra of some 2,2-disubstituted 1,3-dioxolanes, 1,3-dithiolanes and 1,3-oxathiolanes were studied. Especially, the effect of the length of the side chain in ring position 2 of these compounds and the ease of formation of possible lactone/thiolactone ion as a fragmentation product were examined. In addition, two 2,2-disubstituted 1,3-dioxanes were studied to see the effect of the bigger ring size. The formation of lactone ions was more favorable under methane chemical ionization than under electron ionization conditions. The structures of fragment ions and the ions generated from model compounds were carefully studied using both high- and low-energy collision-induced dissociation. Also ab initio molecular orbital calculations up to the HF/6–31G** level of theory for protonated 2-methyl-2-propanoic acid ethyl ester of 1,3-dioxolane, 1,3-oxathiolane and 1,3-dithiolane and for two isomeric bicyclic ions were carried out. The theoretical results obtained favor the formation of the lactone ion. Copyright © 2005 John Wiley & Sons, Ltd.     

Importance of bases on the copper-catalyzed oxidative homocoupling of terminal alkynes to 1,4-disubstituted 1,3-diynes

Copper-catalyzed, solvent-free oxidative homocoupling of terminal alkynes can be performed to 1,3-diynes in good to excellent yields in the absence of any additives, using air as environmentally friendly oxidant and the occurrence of water as an exclusive byproduct in the whole process. It is shown that AcO⁻ of copper (II) acetate catalyst may take the role of base and found that the homocoupling cannot occur using weakly basic copper salt catalysts such as CuBr, CuCl, or CuI. Thus, the bases are absolutely necessary in the process of the homocoupling of terminal alkynes.     

New approach to unsymmetrical 1,3-diazatriphenylenes through intramolecular oxidative cyclodehydrogenation

An efficient synthetic route towards previously inaccessible dibenzo[f,h]quinazolines and [1]benzothieno[3,2-f]benzo[h]quinazolines through FeCl₃-mediated intramolecular oxidative cyclodehydrogenation of readily available 5-([1,1′-biphenyl]-2-yl)pyrimidines and 5-(2-phenylbenzo[b]thiophen-3-yl)pyrimidines is described. Molecular orbital calculations (DFT), as well as redox and photophysical measurements for all new compounds have been performed. The data show that the reported polycyclic systems have a potential to use in organic electronic applications.     

New Approach to the Synthesis of 1,3-Chloroisothiocyanatoalkanes. Synthesis of Tetrahydro-1,3-thiazine-2-thiones and 2-Alkylamino-5,6-dihydro-1,3-thiazines

A method was developed to prepare 1,3-chloroisothiocyanatoalkanes by reducing 1,3-isothiocyanato ketones using sodium borohydride at pH ~7 and subsequent treatment of the resultant 1,3-isothiocyanato alcohols with thionyl chloride. The reaction of 1,3-chloroisothiocyanatoalkanes with sodium hydrosulfide or amines gives substituted tetrahydro-1,3-thiazine-2-thiones or 2-amino-5,6-dihydro-1,3-thiazines.     

Syn-anti isomerism in the 1,3-dipolar cycloaddition to cis-3,4-disubstituted cyclobutenes. : 1. Role of out-of-plane distortions.

Cyclobutenes 1–3 react with diazomethane covering the complete range of facial selectivity. Non planarity of the double bond moiety and consequent energetic asymmetry of out-of-plane distortions, mainly due to π/C-X and π/C-H interactions, parallel the stereochemistry of cycloaddition.     

A novel multicomponent approach to the synthesis of 1,3-thiazolidine-2-thiones

An easy, efficient, and simple one-pot approach for the synthesis of 1,3-thiazolidine-2-thiones via multicomponent reaction is reported. The reaction of a primary amine with carbon disulfide in the presence of dibenzoylacetylene or bis(4-methyl-1-benzoyl)acetylene in a mixture of CH₂Cl₂ and H₂O after 5 h, afforded the title compound as alkene diastereomers.     

A convenient 1,3-dipolar cycloaddition approach to pyridylpyrroles

A variety of 2-, 3-, and 4-pyridylpyrroles were synthesized in good to excellent yields via the 1,3-dipolar cycloaddition of symmetrical and unsymmetrical münchnones and nitroalkenes. The unsymmetrical münchnones show moderate to excellent regioselectivity.     

Convenient approach to chiral 4-monosubstituted 1,3-oxazolidine-2-thiones

Chiral 4-monosubstituted 1,3-oxazolidine-2-thiones are regarded as one of the modified version of Evans auxiliaries in asymmetric aldol condensation, which can generate two adjacent chiral carbon centers in one time They have advantages over Evans auxiliaries in some aspects, however, their application is highly limited by their preparation approaches as toxic or flammable chemicals are involved. Here, a mild and applicable procedure for preparing the chiral oxazolidine-2-thione auxiliaries has been developed in this article. Potassium ethylxanthate and the corresponding chiral amino alcohols as the starting material in absolute ethanol are mixed and the mixture are heated under reflux for 1?h in open air to provide 1,3-oxazolidine-2-thiones chiral auxiliaries in moderate to excellent yields.     

Basis set dependence of the vibrational wavenumbers of the out-of-plane modes of conjugated π-electron ring systems

Basis set dependence of the vibrational wavenumbers of out-of-plane modes calculated at the MP2 level of ab initio molecular orbital theory is examined for benzene, p-benzoquinodimethane, p-benzoquinone, furan, and thiophene. Various polarization functions up to (3df,p) are used in combination with the 6-31G and 6-311G basis sets. It is shown that, especially in the case of normal modes with alternate out-of-plane motions of the carbon atoms (such as the ν₄ (b_2g) mode of benzene), the calculated wavenumbers depend strongly on the exponents (_d) of the d functions on the carbon atoms. It is therefore necessary to include d functions with an optimum exponent (_d0.4) on the carbon atoms to obtain reasonable out-of-plane vibrational force fields. In a few cases (such as the ν₁₆ (a₂) mode of furan), inclusion of a set of f functions on the carbon atoms has some effects on the calculated wavenumbers of out-of-plane modes. However, unless the basis set contains an optimum set of d functions, inclusion of a set of f functions does not improve the agreement between the observed and calculated vibrational wavenumbers. As a case with an exaggerated effect of basis set, it is shown that the wavenumber of the ν₄₁ (b_2g) mode of the planar optimized structure of p-benzoquinodimethane is calculated to be imaginary by using the 6-311G(d,p) or 6-311G(df,p) basis set at the MP2 level. For all the molecules treated in the present study, reasonable out-of-plane vibrational force fields are obtained by using the 6-31G(2df,p) and 6-311G(2df,p) basis sets.     

‘One-flask’ synthesis to 3,5-disubstituted 1,2,4-triazoles from aldehydes with hydrazonoyl hydrochlorides via 1,3-dipolar cycloaddition

A new ‘one-flask’ synthesis of 3,5-disubstituted 1,2,4-triazoles has successfully been developed to synthesize a series of 3,5-disubstituted 1,2,4-triazoles. The transformation involves the 1,3-dipolar cycloaddition reaction of hydrazonoyl hydrochlorides with oxime intermediates prepared from aldehydes with hydroxylamine hydrochloride in the presence of excess amount of triethylamine. In this ‘one-flask’ 1,3-dipolar reaction, hydrazonoyl hydrochlorides was concerned as the masked 1,3-dipole nitrilimine under basic condition. Furthermore, this newly developed methodology can be applied to various aldehyde substrates including aliphatic, cyclic aliphatic, aromatic, and heterocyclic aldehydes.     

Novel approach to the synthesis of 1,3-diazapyrenes

Methods have been developed for the synthesis of 1,3-diazapyrenes based on the reactions of perimidines with ethoxymethylene-1,3-dicarbonyl compounds and also 6(7)-benzoyl(acetyl, formyl)perimidines with carbonyl compounds in PPA. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 79–82, January, 2009.     

One-pot synthesis of 4,5-disubstituted 1,2,3-(NH)-triazoles using terminal acetylenes, carbon monoxide, aryl iodides, and sodium azide

A one-pot method for the synthesis of 4,5-disubstituted-1,2,3-(NH)-triazoles via carbonylative Sonogashira reaction/1,3-dipolar cycloaddition of terminal acetylenes, carbon monoxide, aryl iodides, and sodium azide was developed. A series of new 4,5-disubstituted-1,2,3-(NH)-triazoles were prepared readily under mild conditions.     

1,3-Thiazepines. 6. UV Spectroscopic and Theoretical Study of the Electronic Structures of 2-Aminotetrahydro- and 2-Iminotetrahydro-1,3-thiazepines

On the basis of studies of the electronic absorption spectra and quantum-chemical calculations of the energies and bond orders of a series of N-acetyl-N-aryl substituted 2-amino-4,5,6,7-tetrahydro-1,3-thiazepines and N-aryl substituted 2-iminohexahydro-1,3-thiazepines it has been concluded that the reason for the weak basicity of the ring nitrogen atom of the former is the acceptor properties of the amide carbonyl which obstructs the interaction of the unshared pair (USP) of this atom with the phenyl ring; in the case of the derivatives of hexahydroazepine the strengthening of the basic properties of the exocyclic nitrogen atom is associated with the conjugation of its USP with the -electrons of the benzene ring, which is strengthening by delocalisation of the USP of the sp³-hybridized ring nitrogen atom into the azomethine bond.     

Highly efficient enantioselective synthesis of 1,3-disubstituted 2,5-diketopiperazine derivatives via microwave irradiation

Abstract

Chiral 2,5-diketopiperazine (2,5-DKP) derivatives have a broad range of biological activities in the medicinal field. The synthetic protocols of 1,3-disubstituted 2,5-DKPs via base-catalyzed cyclization of chloroacetamide have been reported. However, there are several drawbacks, such as an overly long reaction time, low to moderate yield, and racemization of the products. The sequence modified herein of 1,3-disubstituted 2,5-DKPs involves microwave-assisted cyclization. It increases yields and reduces reaction time. Furthermore, employing N-PMB protection prevents racemization, which frequently occurs in the base-catalyzed cyclization reaction. Consequently, the rapid synthetic method of enantiomerically pure 1,3-disubstituted 2,5-DKPs via microwave reaction was established successfully.