Constantin Drăghici

Primary cycloadducts of 1,10-phenanthrolinium and phthalazinium phenacylides with DMAD

Primary cycloadducts cis-2 and trans-6 of monosubstituted cycloimmonium phenacylides 1 and 5 with DMAD have been obtained for the first time. They isomerise stereospecifically and regiospecifically by prototropic rearrangement to dihydro derivatives cis-3 and trans-7, respectively. The new heterocyclic system of pyrrolo[1,2-a][1,10]phenanthroline was illustrated by a series of derivatives (8a–f). The ethyl (8b) and isopropyl (8c) esters exhibit helical chirality by 1H NMR.

Stereochemistry of cyclobutanone resulted from cycloadditions of t-butylcyanoketene to bicyclo[2.2.1]heptene derivatives, as evidence for a π2s+π2a reaction mode

Abstract The stereochemistry of the cyclobutanones 1-7, resulted from the reaction of t-butylcyanoketene with bicyclo[2.2.1]heptene, bicyclo[2.2.1]heptadiene, 1,4 - dihydro - 1,4 - methanonaphthalene, 1,4 - dihydro - 9 - (1 - methylethylidene) - 1,4 - methanonaphthalene, 1,4 - dihydro - 1,4 - epoxynaphthalene, l,4,4a,8b - tetrahydro - 1,4 - methanobiphenylene (lα,4α,4aα,8bα) and 1,4,4a,8b - tetrahydro - 1,4 - methanobiphenylene(1α,4α,4aβ,8bβ) was established as having the cyclobutanone ring exo and the t-Bu group in the α configuration. These findings represent a stereochemical argument in favour of a π 2 s + π 2 a reaction mode of t-butylcyanoketene to the above mentioned bicyclo[2.2.1]heptene derivatives. Observations regarding preservation of the original configurations of alkenes as well as the geometrical distorsion of the cyclobutanones are shortly discussed.

A2BA2 Block Copolymers of Poly(N-isopropylacrylamide) (A) and Poly(ethylene glycol) (B): Synthesis and Thermal Gelation Properties of Aqueous Solutions

A2BA2 block copolymers of poly(N-isopropylacrylamide) (A, PNIPAM) and poly(ethylene glycol) (B, PEG) were synthesized by SET-LRP for the first time. The 1H-NMR and GPC analyses showed that the block copolymers prepared had in average 3.5–3.8 PNIPAM arms/macromolecule and low polydispersities (Mw/Mn=1.25–1.35). The thermogelation behavior of their 20 wt% aqueous solutions was investigated by DSC, dynamic rheometry and the tube inversion method as a function of the molecular weight of both PEG block and PNIPAM arms. The results showed that both phase transition temperature, as determined by DSC, and gelation temperature, determined by the tube inversion method, increased with the PEG block length and decreased with the MW of the PNIPAM arms, while the forming gels were more stable for longer PEG chains. By comparing the thermoresponsive properties of the H-shaped block copolymers synthesized with those of some linear PNIPAM-PEG-PNIPAM triblock copolymers of similar molecular weights of both PNIPAM side blocks and PEG middle chain, almost identical results were obtained, indicating practically no influence of the shape of the PNIPAM blocks from this point of view.

Benzoannelated valence isomers of homoannulenes Part IV. Flow vacuum pyrolysis of 1,2,3,3a,8,8a-hexahydro-2,3,8-methenocyclopentindene☆

Abstract Pyrolysis of 1,2,3,3a,8,8a-hexahydro-2,3,8-methenocyclopentindene in a flow system at 1.33 mbar, in an argon atmosphere and at temperatures between 500 and 750 °C was studied by GC/MS. The first pyrolysis product, 1,6-dihydro-1,6-methanobenzo[ d ]cyclooctene (a new compound), was converted at elevated temperatures into mainly α- and β-allylnaphthalenes and fluorene. A reaction mechanism including radical and concerted steps is suggested.

New carbocyclic N(6)-substituted adenine and pyrimidine nucleoside analogues with a bicyclo[2.2.1]heptane fragment as sugar moiety; synthesis, antiviral, anticancer activity and X-ray crystallography.

New nucleoside analogues with an optically active bicyclo[2.2.1]heptane skeleton as sugar moiety and 6-substituted adenine were synthesized by alkylation of 6-chloropurine intermediate. Thymine and uracil analogs were synthesized by building the pyrimidine ring on amine 1. X-ray crystallography confirmed an exo-coupling of the thymine to the ring and an L configuration of the nucleoside analogue. The library of compounds was tested for their inhibitory activity against influenza virus A∖California/07/09 (H1N1)pdm09 and coxsackievirus B4 in cell culture. Compounds 13a and 13d are the most promising for their antiviral activity against influenza, and compound 3c against coxsackievirus B4. Compounds 3b and 3g were tested for anticancer activity.

New carbocyclic nucleoside analogues with a bicyclo[2.2.1]heptane fragment as sugar moiety; synthesis, X-ray crystallography and anticancer activity.

An amine group was synthesized starting from an optically active bicyclo[2.2.1]heptane compound, which was then used to build the 5 atoms ring of a key 6-chloropurine intermediate. This was then reacted with ammonia and selected amines obtaining new adenine- and 6-substituted adenine conformationally constrained carbocyclic nucleoside analogues with a bicyclo[2.2.1]heptane skeleton in the sugar moiety. X-ray crystallography confirmed an exo-coupling of base to the ring and a L configuration of the nucleoside analogues. The compounds were tested for anticancer activity.

RuO4-mediated oxidation of N-benzylated tertiary amines. 3. Behavior of 1,4-dibenzylpiperazine and its oxygenated derivatives

Abstract1,4-Dibenzylpiperazine (1),-2-piperazinone (7),-2,6-piperazinedione (9), and 1-benzoyl-4-benzylpiperazine (30) were oxidized by RuO4 (generated in situ) by attack at their endocyclic and exocyclic (i.e., benzylic) aminic N-α-C-H bonds to afford various oxygenated derivatives, including acyclic diformamides, benzaldehyde, and benzoic acid. The reaction outcome was complicated by (i) the hydrolysis of diformamides, occurred during the work-up, and (ii) the reaction of benzaldehyde with the hydrolysis-derived amines giving imidazolidines and/or Schiff bases. Benzoic acid resulted from benzaldehyde only. Compounds 7, 30, and 1-benzylpiperazine, but not 9, were transiently formed during the oxidation of 1. In the same reaction conditions, 1,4-dibenzyl-2,3-(or 2,5)-piperazinedione, 1,4-dibenzyl-2,3,6-piperazinetrione, 4-benzyol-1-benzyl-2-piperazinone, and 1,4-dibenzoylpiperazine were inert. The proposed oxidation mechanism involves the formation of endocyclic and exocyclic iminium cations, as well as of cyclic enamines. The latter intermediates probably result by base-induced deprotonation of the iminium cations, provided an N+−β-proton is available. In the case of 1, the cations were trapped with NaCN as the corresponding α-aminonitriles. The statistically corrected regioselectivity (endocyclic/exocyclic) of the RuO4-induced oxidation reaction of 1, 7, and 30 was 1.2–1.3.

Stereochemistry of the t-butylcyanoketen cycloaddition to norbornene

The stereochemistry of the title cycloaddition has been determined by lanthanide-induced shift experiments; the cyclobutanone ring is exo, while the t-butyl group is pointing towards the methylene bridge of norbornane.

The Effect of Hydrophilic Bentonite Nanoclay on the Thermogelation Properties of Poly(N-isopropylacrylamide)-poly(ethylene glycol)-poly(N-isopropylacrylamide) Triblock Copolymer Aqueous Solutions

The effect of hydrophilic bentonite addition on the thermogelation properties of aqueous solutions of poly(N-isopropylacrylamide)–poly(ethylene glycol)–poly(N-isopropylacrylamide) (PNIPAM-PEG-PNIPAM) triblock copolymers of various compositions and molecular weights was investigated. Dynamic rheometry and differential scanning calorimetry (DSC) measurements showed that increasing concentrations of clay added to 20 wt.% polymer aqueous solutions caused a decrease of the temperature at which the viscosity starts increasing, while the temperature corresponding to the maximum endothermic effect due to the PNIPAM chain dehydration remained practically unchanged. The storage modulus, G′, increased with clay concentration for shorter PNIPAM chain triblock copolymers, while an opposite situation occurred in the case of the block copolymer with the longest PNIPAM block. For bentonite concentrations above 1 wt.%, G′ was larger than the viscous modulus, G″, at temperatures higher than the phase separation temperature, indicating a predominantly elastic character of the resulting composite hydrogels. These findings were explained through the presence of polymer–clay interactions occurring mainly through the PEG blocks.

A long-range tautomeric effect on a new Schiff isoniazid analogue, evidenced by NMR study and X-ray crystallography

Long-range tautomerism to a N,O-aminal thereby closing a tetrahydrofuran ring was evidenced for an isoniazid analogue, whose accidental synthesis is presented in the paper. The isoniazid analogue was synthesized by the reaction of isoniazid with 2-hydroxy-tetrahydrofuran which was demonstrated to exist in old THF together with other peroxides, especially 2-HOO-THF. The same compound was efficiently obtained from a THF containing 2-HOO-THF, by reducing this peroxide in the presence of isoniazid. The 2,4-dinitrophenylhydrazone was also synthesized. The oxidation of 1,4-butanediol and the reaction of the resulting mono-aldehyde with isoniazid gave the same compound. The existence of the linear tautomer was evidenced in the NMR spectra in DMSO-d6 and was confirmed by X-ray analysis to be the single tautomer in the crystal. The cyclic N,O-aminal tautomer was found in the NMR spectra in CDCl3, resulting from an intramolecular HCl-catalyzed addition of the hydroxyl group to the double bond CHN of the linear tautomer, thereby closing a tetrahydrofuran ring. This is a favoured cyclization according to Baldwins rules (5-exo-trig). The same tautomerism was also present for two isoniazid analogues obtained from two lactols, used in prostaglandin synthesis. The compounds 1, 4, 6 and INH had no antibacterial or antifungal activity.