Prof. dr. Costel Moldoveanu

Project reports

• 2012. Stage II. Synthesis and structural analysis of imidazolium salts and of pyrroloimidazole cycloadducts. Testing the properties, structural analysis and theoretical study of fluorescence for the synthesized compounds:

II.1. Synthesis of imidazolium salts by quaternization of the N3 of imidazole derivatives (obtained in stage I.1. or I.2.) using conventional heating.
In this stage were synthesized some salts derived from imidazole 4 and benzimidazole 5 by quaternization of the the second nitrogen atom from the previosly obtained derivatives 1 (2) with halogenoderivatives with increased reactivity 3 such as halogeno-amides and halogeno-esters (iodoacetamide and methyl- or ethyl bromoacetate, respectively).

The new imidazole and benzimidazole derivatives alchylated in 3 position were obtained with good to very good yields (between 80 and 95 %). The mainly disadvantage of this reactions is the long reaction time 36 hours for imidazole and 48 hours for benzimidazole when the reaction solvent is acetone.

In order to reduce the reaction time we used an unconventional synthetic method – under ultrasound irradiation. Ultrasound irradiation induces a remarkable acceleration for reactions, the reaction times decreases dramatically, from 36-48 hours to 30-45 minutes. Also, under ultrasound irradiation the yields are higher with up to 10%.

A new, efficient and general method for preparation of 1,3-diazol salts via N-alkylation reactions using ultrasound irradiation was elaborated. Under ultrasound the reaction time decreases substantially, the yields are high and the reaction conditions are mild.

The structure of the compounds was proven by elemental (C, H, N) and spectral analysis. The following spectroscopic methods were used: IR, MS, 1H NMR, 13C NMR, 15N NMR and two-dimensional experiments 2D-COSY, 2D-HETCOR (HMQC), long range 2D-HETCOR (HMBC). All the elemental and spectral data are in accordance with the proposed structure.

II.2. si II.3. Synthesis of cycloadducts derived from imidazolium salts (obtained in stage II.1.) by [3+2] dipolar cycloaddition with activated alkynes symmetrically and unsymmetrical substituted by conventional heating and under ultrasound irradiation.

In this stage was investigated the reaction of the benzimidazolium salts 5d with dimethylacetilenedicarboxilate (DMAD). We have done first the reaction in chloroform, and the reaction product is the totally aromatized and in the same time with the ester group from the first position hidrolized 6.

In order to elucidate the influence of the solvent over the hydrolisis that occurs, we repeated the reaction in benzene and in methanol. In benzene we obtained only the hydrolyzed product 6, while in methanol we have obtained both hydrolyzed 6 and un-hydrolyzed cycloadduct 7. Un-hydrolyzed product is the minor product.

We have also investigated the reaction of the salts 4a and 5a with dimethylacetylendicarboxilate (DMAD) and methyl propiolate. In present we work on product separation and identification.

II.4., II.5. si II.6. Synthesis of cycloadducts derived from imidazolium salts (obtained in stage II.1.) by [3+2] dipolar cycloaddition with activated alkenes symmetrically and unsymmetrical substituted by conventional heating and under ultrasound irradiation a comparative study.

We investigated the reaction of the salt 5a with N-ethylmaleineimide(NEtMI). In present we work on product separation and identification.

II.7. Theoretical study regarding fluorescent properties and absorption spectra of the pyrroloimidazolic derivatives.

Using the mecano-cuantic calculations at (C)PCM TD-DFT theory level we work on geometry optimization of the molecules. Then for the energetic minimized molecules we will calculate the absorption and emission spectra. The calculated spectra will be compared with the experimental one. We will try that based on theoretical calculation to predict if a molecule have or not fluorescent properties. Since the molecule under study are big, the mecano-cuantic calculations are complexes and require very long time.

II.8. Testing the biological activity (possible growth factor, antibacterial and antifungal activity) of the new obtained compounds.

In this research area, for germination test, two type of seeds with different biological structures were used: Picea abies (spruce) characterized through woody plants with free seeds, not included in fruit, and Triticum aestivum (wheat), characterized through grassy plants with the seeds included in ovarian cavity.

Regarding the concentration used for germination test, following values were used: 10^-3M, 5×10^-4 M, 10^-4M, 5×10^-5M and 10^-5M.

A first remark is that there was no significant differences between the number of the germinated seeds on all tested samples comparing with the blank sample. The concentration values from 10^-3M – 5×10^-4M range have toxic effect, both on hypocotyls and radicles, the roots being more sensitive on higher concentration.

On spruce seeds test, imidazole and benzimidazole had different action: imidazole had a low stimulative effect over the hypocotyls and a strong inhibitor effect over the radicles, benzimidazole had an opposite behavior having a low inhibitor effect over the hypocoltyls and strong stimulative effect over the radicles.

The alkylation of the nitrogen atom from the first position of the imidazole, both on imidazole and benzimidazole case, with acrylonitryl, methyl or ethyl acrylate, cause a stimulative effect over the hypocotyls. By quaternization of the nitrogen atom N3 of the cianoethylimidazole with methyl or ethyl bromoacetate, a strong stimulative effect over the hypocotyl lenght an a low stimulative efect over the spruce radicles. In the case of the benzimidazole the effects of the quaternization are insignificant. When the quaternization was made with iodoacetamide, all obtained compounds, no matter on which concentration values, had strong inhibitor effect over the both hypocotyls and especially over the radicles.

In the case of the germination tests on wheat seeds both imidazole and especially benzimidazole had stimulative effect.

The alkylation of the nitrogen atom from the first position of the imidazole with acrylonitryl the stimulative effect is insignificant comparing with blank sample, while on the alkylation with ethyl and especially methyl acrylate the resulted products have a stimulative effect with up to 30 % over the hypocotuls length. In the case of the benzimidazole all alkylated products at N1 have strong stimulative effect over the hypocotyls length.

By quaternization of the nitrogen atom N3 of the cianoethylimidazole with methyl or ethyl bromoacetate, a strong stimulative effect over the hypocotyl lenght. In the case of the benzimidazole the effects of the quaternization are insignificant. When the quaternization was made with iodoacetamide, all obtained compounds, no matter on which concentration values, had strong inhibitor effect over the hypocotyls.

II.9. The structure of the compounds was proven by elemental (C, H, N) and spectral analysis. The following spectroscopic methods were used: IR, MS, 1H NMR, 13C NMR, 15N NMR and two-dimensional experiments 2D-COSY, 2D-HETCOR (HMQC), long range 2D-HETCOR (HMBC). All the elemental and spectral data are in accordance with the proposed structure.

The web page of the project was transferred to the following address: http://teclu.chem.uaic.ro/moldoveanu/contract-te/. Here was published the final report of this stage.

II.10. A part of the obtained results were organized and presented on a series of national and international conferences as following:

1. C. Moldoveanu, Ghe. Zbancioc, D. Mantu, I. Mangalagiu: NMR Study on structure elucidation of new imidazole ligands The XVII-th International Conference „Physical Methods in Coordination and Supramolecular Chemistry” (PPMCSC-XVII), Chisinau, 24 – 26 Octombrie 2012, (Poster P62).
2. I. Stoian, P. M. Stiuleac, I. O. Silea, Ghe. Zbancioc, C. Moldoveanu, I. Mangalagiu: Ultrasound assisted synthesis of new imidazolium salts Zilele Universitatii “Al. I. Cuza-Iasi“, 25 – 26 Octombrie 2012, (Poster P29).
3. Moldoveanu, C.; Zbancioc, Ghe.; Maftei, D.; Stoian, I.; Mangalagiu I.: „Synthesis of new imidazole derivarives possible ionic liquids using ultrasound irradiation”; XXXII-st Romanian Chemistry Conferance 3-5 october 2012, Calimaneşti-Caciulata, Valcea, Romania (Poster presentation P.S.I. 16).
4. Moldoveanu, C.; Zbancioc, G.; Antoci, V.; Mangalagiu, I.: „Ultrasound assisted synthesis of new ionic liquids imidazole based” 11th International Conference on Global Research and Education Interacademia  27-30 August 2012, Budapest Hungary. (oral presentation)
5. Zbancioc, G.; Moldoveanu, C.; Mantu D.; Mangalagiu, I.: „Microwave assisted synthesis of new highly fluorescent pyrrolo-imidazole” 11th International Conference on Global Research and Education Interacademia  27-30 August 2012, Budapest Hungary. (poster)
6. Zbancioc, G.; Moldoveanu, C.; Stiuleac P. M.; Silea I. O.; Mangalagiu, I.: „Syhnthese de nouveaux pyrrolo-imidazole derives avec des prpprietes de fluorescence”; Septieme Colloque Franco-Roumain de Chimie Apliquee 27-29 juin 2012, Bacau, Roumanie (Poster 25, pp 70).
7. Moldoveanu, C.; Zbancioc, G.; Stoian I.; Mangalagiu, I.: „Syhnthese assistee par ultrasons de nouveaux liquides ioniques  derives de l’imidazole”; Septieme Colloque Franco-Roumain de Chimie Apliquee 27-29 juin 2012, Bacau, Roumanie (Poster 13, pp 47).

From the above mentioned result that all proposed objectives were achieved in 100%.