XIX INTERNATIONAL SYMPOSIUM

„ADVANCES IN THE CHEMISTRY OF

HETEROORGANIC COMPOUNDS”

ORGANIZED BY

Centre of Molecular and Macromolecular Studies Polish Academy of Sciences

Section of Heteroorganic Chemistry

Polish Chemical Society

in cooperation with

Faculty of Chemistry University of Łódź

and Łódź Branch Polish Chemical Society

ŁÓDŹ

November 25, 2016

 

Printed by PROXIMA Sp.z o.o., Krańcowa 55, 94-305 Łódź, 2016.

ISBN 978-83-7455-520-3

http://www.cbmm.lodz.pl/

 

XIX International Symposium “Advances in the Chemistry of Heteroorganic Compounds”

is dedicated to

Professor Jerzy Wicha

on the occasion of his 80th birthday

and

Professor K. Michał Pietrusiewicz

on the occasion of his 70th birthday

 

Conference Chairman Józef Drabowicz

Organizing Committee Bogdan Bujnicki

Jacek Chrzanowski

Tomasz Cierpiał

Piotr Kiełbasiński

Dorota Krasowska

Jerzy Krysiak

Piotr Łyżwa

Wanda H. Midura

Patrycja Pokora-Sobczak

Sponsored by

 

XIX International Symposium

“Advances in the Chemistry of Heteroorganic Compounds”

Łódź, November 25, 2016 Programme

9:00 – 9:30 OPENING SESSION I – chairman: Marian Mikołajczyk

9:30 – 10:15 PL-1

Kin-ya Akiba Hiroshima University and Waseda University, Japan

Chemistry of Hypervalent Compounds: Examples from Pseudorotation, Ligand Coupling, and Hypervalent Carbon

Species

10:15 – 11:05 PL-2 Herbert Mayr

Ludwig-Maximilians-Universität München, Germany Philicities, Fugalities, and Equilibrium Constants

11:05 – 11:35 COFFEE BREAK SESSION II – chairman: Tadeusz Gajda

11:35 – 12:20 PL-3 Manfred Scheer

Universität Regensburg, Germany Polyphosphorus Complexes for Supramolecular Aggregations

12:20 – 13:05 PL-4 Lothar Weber

Universität Bielefeld, Germany Fiat lux-luminescent 1,3,2-benzodiazaboroles

13:05 – 14:05 LUNCH 14:05 – 15:20 POSTER SESSION

SESSION III – chairman: Janusz Zakrzewski

15:20 – 15:50 IL-1

Anka Pejović University of Kragujevac, Serbia

Syntheses and antimicrobial/cytotoxic assessment of ferrocenyl oxazinanes, oxazinan-2-ones,

and tetrahydropyrimidin-2-ones

15:50 – 16:20 IL-2

Oleg M. Demchuk Maria Curie-Skłodowska University, Poland

Phosphine-borane complexes as the intermediates in the synthesis of phosphorus ligands. Experimental

and mechanistic approaches 16:20 CLOSING

PL - plenary lecture, IL - invited lecture

 

PLENARY LECTURES

PL-1 

Chemistry of Hypervalent Compounds: Examples from Pseudorotation, Ligand Coupling,

and Hypervalent Carbon Species Kin-ya Akiba1,2

1 Professor Emeritus, Hiroshima University, Japan. 2 Invited Researcher, Waseda University, Japan.

akibaky5564@gmail.com; ak-y@lapis.plala.or.jp

Hypervalent compounds are main group element (sp element: Groups 1,2, and 13-18)

compounds that contain a number (N) of formally assignable electrons of more than the octet in a valence shell of the central atom (X) in directly bonding a number (L) of ligands (substituents). The N-X-L designation is a convenient and useful formalism.

Thus, he (Prof. Akiba) has chosen B, C; S, P, Si; Sn, As, Sb, Bi; Te. Hence I am convinced that he is the best choice as editor for this book. (Taken from the FOREWORD by the late Professor Sir Derek H. R. Barton and the PREFACE of the book Chemistry of Hypervalent Compounds, 1999, Wiley-VCH). 1: Apicophilicity and Pseudorotation

apical XPH

HHH H

PH

equatorial XHH

X (apicophilicity): F > H > OH (OR) Cl > NR2 > Ph > H O- > Me

1P2

5 43

TBP 12

5P5

1

243 5

P52

4

3 4P3

5 21

TBP 43

3P4

5 12

43C4v 34

1

2: Synthesis of O-cis (antiapicophilic) and O-trans Phosphoranes

2RLiPO

OH

F3C

CF3

CF3

F3C

PO

CF3F3C

RO

F3CF3C

I2 PO

CF3F3C

IRO

F3CF3C

PO

OR

F3C CF3

: BPRPO

OR

F3C

CF3

CF3

F3CF3CF3C

O-cis O-trans 3: Reactions of Phosphoranes

a) synthesis of Z-isomer

CH2CO2R1P

O

OCF3

F3C

F3C

CF3

PO

OCF3

F3C

F3C

CF3H

OR1O P

OO

OF3C

CF3F3C

CF3

H

CO2R1R2

Hbase

R2CHO

M+ M+

R2 CO2R1 OMP

O

OCF3

F3C

F3C

CF3

+

Z-isomer

b) reaction with oxygen

PL-1 

c) reaction with benzoyl chlorid

X Y 4: Ligand Coupling of Pentavalent Stiboranes

SbAr

Ar

Ar

Tol

Ar

Ar-Ar

SbAr

Ar

Tol

Ar

ArSbTol

Ar

Ar

Tol

TolSbTol

Ar

Tol

Ar

Tol

Ar-Tol Ar-Ar Ar-Tol

_Ar2TSb

_ArT2Sb

SbAr

Ar

Ar

Tol

TolSbAr

Ar

Tol

Tol

Ar

SbAr

Tol

Tol

Ar

ArSbAr

Tol

Tol

Tol

Ar

_Ar3Sb _T3Sb _T2ArSb

_Ar2TSb

76 : 24

58 : 4236 : 64

not observed not observed

A

B

C

A:

B:C:

5: Formation of Penta- and Hexavalent Carbon Species References [1] Chemistry of Hypervalent Compounds, 1999, Wiley-VCH. [2] Studies on Hypervalent Compounds and Synthetic Work Using Heteroaromatic Cations,

Heteroatom Chemistry, 2011, 22(3/4), 207-274. [3] Organo Main Group Chemistry, 2011, Wiley.

PO

O

F3C CF3

F3CF3C

P

O

O

F3C

CF3

CF3

F3C

POO

CH2Ph

F3C CF3

F3CF3C

O-cis

PO

O

F3C

CF3

CF3

F3C

BuLiPO

OF3C CF3

F3CF3C

O

PhCOClO

S C

O

OS

O

O

S C

O

OS

Me

Me

Me

OMe

Me

+2

Me Me2 MeX

2 X-

O

MeMe

Me

OOMeMe OH

XX

HClO4 orHBF4

OCOMe Me

XX

ClO4- orBF4-

a) X=Cl b) X=F dark green solid

PL-2 

Philicities, Fugalities, and Equilibrium Constants Herbert Mayr1

1 LMU München, Department Chemie, Butenandtstr. 5-13, 81377 München, Germany herbert.mayr@cup.lmu.de

Our understanding of polar organic reactivity is based on relationships between rate and equilibrium constants. Thus, strong bases are generally considered to be good nucleophiles as well as poor nucleofuges. Though exceptions from this general rule have long been known, a systematic analysis has been problematic, because rate constants for the reactions of nucleophiles with C-centered electrophiles have often been correlated with Brønsted basicities (i. e., affinities towards the proton). For that reason, the origin of deviations from Brønsted correlations could often not unambiguously be assigned.

 

In the last two decades, we have created comprehensive nucleophilicity,1 nucleofugality,2 and Lewis basicity scales3 by using differently substituted benzhydrylium ions with widely variable reactivity but equal steric demand as reference electrophiles,1 electrofuges,2 and Lewis acids.3 Relationships between these kinetic and thermodynamic parameters will be discussed with emphasis on examples where the commonly assumed proportionalities break down.4

I will discuss the origin of several counterintuitive phenomena, e.g. why strong nucleophiles can also be good nucleofuges, and why weak nucleophiles sometimes substitute strong nucleophiles in SN2 reactions. It will be shown that solvolysis rate constants of alkyl bromides and chlorides, but not of carboxylates provide accurate information about thermodynamic stabilities (more precise: Lewis acidities) of carbocations. Eventually it will be discussed why carbocations, which are formed slowly in SN1 reactions are not always good electrophiles. The role of intrinsic barriers for controlling organic reactivity will be analyzed. References [1] http://www.cup.uni-muenchen.de/oc/mayr/DBintro.html. [2] Streidl, N.; Denegri, B.; Kronja, O.; Mayr, H.; Acc. Chem. Res. 2010, 43, 1537-1549. [3] Mayr, H.; Ammer, J.; Baidya, M.; Maji, B.; Nigst, T. A.; Ofial, A. R.; Singer, T.; J. Am. Chem. Soc. 2015, 137, 2580-2599. [4] Mayr, H.; Ofial, A. R.; Acc. Chem. Res. 2016, 49, 952-965.

PL-3 

Polyphosphorus Complexes for Supramolecular Aggregations Manfred Scheer1*, Claudia Heindl1, Barbara Kremer1, Sebastian Heinl1

1 Institute of Inorganic Chemistry, University of Regensburg, Regensburg, Germany.

manfred.scheer@chemie.uni-r.de

Polyphosphorus complexes are an important class of compounds useful for many applications. Due to the lone pairs at the phosphorus atoms, they are able to self-assembly with Lewis acidic transition metal and main group moieties. Here, two different directions have been discovered; (i) the generation of organometallic-organic hybrid compounds as 2D and 3D materials[1,2] and (ii) the creation of molecular giant spheres.[3]

The talk will mainly focus on the second area. Here, the advantages of the five-fold symmetric building block of the pentaphosphaferrocenes are used to create, with Cu(I) and Ag(I) units, unprecedented giant spheres, which exhibit a fullerene-like topology constructed by non-carbon atoms (Figure 1). Although usually template-controlled encapsulation occurs, novel strategies are also successful in the absence of appropriate templates.[4,5] Moreover, many exceptions were found in which the obtained superspheres showed structures beyond the fullerene-topology.

Figure 1. Molecular structure of a supersphere.

References [1] B. Attenberger, S. Welsch, M. Zabel, E. Peresypkina, M. Scheer, Angew. Chem. Int. Ed.

2011, 50, 11516. [2] B. Attenberger, E. V. Peresypkina, M. Scheer, Inorg. Chem. 2015, 54, 7021. [3] A. Schindler, C. Heindl, G. Balázs, C. Gröger, A. V. Virovets, E. V. Peresypkina, M. Scheer,

Chem. Eur. J. 2012, 18, 829. [4] C. Heindl, E. V. Peresypkina, A. V. Virovets, W. Kremer, M. Scheer, J. Am. Chem. Soc.

2015, 137, 10938. [5] S. Heinl, E. Peresypkina, M. Scheer, Angew. Chem. Int. Ed. 2015, 54, 13431.

PL-4 

Fiat lux-luminescent 1,3,2-benzodiazaboroles Lothar Weber1, Johannes Halama1, Lena Böhling1, Mark A. Fox2

1 Faculty of Chemistry, University of Bielefeld, Germany. 2Department of Inorganic Chemistry, University of Durham, England.

lothar.weber@uni-bielefeld.de

The interest in species I containing 1,3,2-benzodiazaborole building blocks has recently

increased because of their potential use as emitting materials in optoelectronic devices.

 

In the vast majority, these heterocycles behave as π-donors towards accepting groups X, when linked by a π-conducting spacer. With R = C2H5 or C6H5 prominent acceptors are aryl, thienyl, dimesitylboryl or ortho-carboranyl functions. The introduction of perfluoroaryl groups as substituents at the N atoms, however, imposes acceptor qualities on the benzodiazaborolyl unit, which are comparable to that of the familiar BMes2 group. The luminescence of the title compounds is highly solvent dependent featuring Stokes shifts up to 20000 cm-1. The relationship between the molecular structures and some photophysical properties of the here presented compounds are discussed. References L. Weber, Coord. Chem. Rev., 2015, 284, 236.

 

INVITED LECTURES

IL-1 

Syntheses and antimicrobial/cytotoxic assessment of ferrocenyl oxazinanes, oxazinan-2-ones, and tetrahydropyrimidin-2-ones

Anka Pejović1,2, Dragana Stevanović2, Ivan Damljanović2, Aleksandra Minić2, Jovana Jovanović2, Sławomir Kaźmierski3, Józef Drabowicz1,3

1 Faculty of Mathematics and Natural Sciences, University of Kragujevac, Kragujevac, Serbia. 2 Jan Dlugosz University in Czestochowa, Czestochowa, Poland.

3 Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Lodz, Poland. anka.pejovic@gmail.com

1,3-Aminoalcohols represent versatile synthons in organic chemistry.1,2 In this paper

we are going to present the preparation on the 3-arylamino-1-ferrocenylpropan-1-oles 1, their transformation into the corresponding ferrocene-containing heterocycles, including 1,3-oxazinanes 2, 1,3-oxazinan-2-ones 3, and tetrahydropyrimidin-2-ones 4. Evaluation of their antimicrobial and cytotoxic properties will be also discussed.

References [1] C. Cimarelli, G. Palmieri, E. Volpini, Tetrahedron 2006, 62, 9423. [2] S. R. Yong, A. T. Ung, S. G. Pyne, B. W. Skeltonb, A. H. White, Tetrahedron 2007, 63,

5579.

IL-2 

Phosphine-borane complexes as the intermediates in the synthesis of phosphorus ligands. Experimental and mechanistic approaches

Oleg M. Demchuk1 1 Department of Organic Chemistry, Maria Curie-Skłodowska University, 33 - Gliniana Street,

20-614 Lublin. oleh.demchuk@umcs.lublin.pl

Phosphines are popular class of ligand used in transition metal mediated catalysis as well as organocatalysts in other transformations [1]. There are many different approaches leading to desirable phosphines and many of them are based on utilization of borane protected phosphorus (III) building blocks and intermediates [2]. Phosphine boranes are therefore considered, by many authors, as convenient derivatives, which could be used in the syntheses instead of air sensitive phosphines. The liberation of target phosphine from intermediate borane complexes is realised at last step of the synthesis by treatment of corresponding borane with super acids (HBF4) or strong Lewis base at elevated temperature. Nevertheless, those usual deprotection techniques are not suitable with more substituted phosphines and furthermore requires a purification steps.

Herein we are presented the simplest but universal, mild and high yielding method of synthesis and liberation of tertiary phosphines from the corresponding borane complexes which does not require any post-reaction purification and tolerates a wide pallet of function groups. The metathesis reaction of series achiral and enantiopure phosphine boranes with trimethylphosphine had been carefully studied. Based on collected kinetic data as well as on advanced quantum chemical calculations the SN2-like reaction mechanism leading though non-polar single transition step (TS) had been proposed. The details of experimental and theoretic studies will be discussed.

Figure 1. TS.

Acknowledgements The financial support from the Polish National Science Centre grant number 2012/05/B/ST5/00362 is gratefully acknowledged. References [1] Phosphorus(III) ligands in homogeneous catalysis : design and synthesis / edited by Paul C.

J. Kamer & Piet W. N. M. van Leeuwen. 2012 John Wiley & Sons, Ltd.

[2] Phosphorus Chemistry II Synthetic Methods / edited by J.-L. Montchamp. 2015 Springer.

 

POSTERS

P-001

Synthesis and properties of novel 2-cyano-3-(10-(aryl)anthracen-9-yl)acrylic acid

Dorota Zając 1, Agnieszka Jędrychowska 1, Jadwiga Sołoducho 1* 1 Wrocław University of Science and Technology, Faculty of Chemistry,

Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.

Due to the outstanding photoluminescence, electrolumine-scence and transport properties, good thermal stability and electrochemical properties, the anthracene derivatives are widely used in optoelectronic devices (e.g. solar cells [1], biofuel cells [2], chemosensors [3] and organic light-emitting diodes [4]). In present work we have presented design and synthesis of a series of new asymmetric anthracene derivatives (4a-g) with an anthracene core and a cyanoacrylic acid group [5]. Electrochemical and photophysical properties for several compounds have been studied in details.

References [1] L. Ai, X. H. Ouyang, Q. D. Liu, et al, Dyes and Pigments 2015, 115, 73-80. [2] R. C. Reid, S. D. Minteer, B. K. Gale, Biosensors and Bioelectronics, 2015, 68, 142–148. [3] J. Prabhu, K. Velmurugan, R. Nandhakumar, Spectrochimica Acta Part A 2015, 144, 23–28. [4] Z. Zhang, W. Jiang, X. Ban, et al, RSC Adv. 2015, 5, 29708 -29717. [5] D. Zając, J. Sołoducho, T. Jarosz, et al, Indian J. Appl. Res., 2016, 6, 395-403.

P-002

A simple and effective synthesis of α,β-diaminophosphonates from t-butyl 2-diethoxyphosphoryl-2-alkenoates

Dariusz Deredas1, Henryk Krawczyk1 1 Institute of Organic Chemistry, Lodz University of Technology

90-924 Łódź, Żeromskiego 116, Poland. dariusz.deredas@p.lodz.pl

Synthetic applications of alkyl 2-diethoxyphosphoryl-2-alkenoates are well documented in the

literature. These compounds have found use as acceptors in Michael-type conjugate addition and proved to be very useful intermediates in the synthesis of many important acyclic, carbocyclic and heterocyclic compounds[1-3].

In our communication we report a simple, highly effective and general method for the synthesis of N-protected vicinal α,β-diaminophosphonates starting from easily accessible t-butyl 2-diethoxyphosphoryl-2-alkenoates. The protocol includes TBD (1,5,7-triazabicyclo[4.4.0]dec -5-ene) promoted Michael addition of phtalimide, subsequent hydrolysis of carboxylate moiety and Curtius rearrangement. The selective mode of deprotection of the N-protected α,β-diaminophosphonates will be also presented.

References [1] T. Minami; T. Okauchi; R. Kouno, Synthesis 2001, 349-357. [2] T. Janecki; J. Kędzia; T. Wąsek, Synthesis 2009, 1227-1254. [3] T. Janecki; A. Albrecht; J.F. Koszuk; J. Modranka; D. Słowak, Tetrahedron Lett. 2010, 51,

2274-2276.

P-003

Cymantrene and Cyrhetrene Nucleobase Conjugates with Activity Against Trypanosoma brucei

Artur Jabłoński1, Łukasz Szczupak1, Dietmar Steverding2, Sebastian Saloman3, Alexander Hildebrandt3, Heinrich Lang3, Agnieszka Rybarczyk-Pirek4,

Valerije Vrcek5, Konrad Kowalski1 1 Faculty of Chemistry, Department of Organic Chemistry, University of Łódź, Tamka 12,

91-403 Łódź, Poland. 2 Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7UQ, UK.

4 Faculty of Chemistry, Department of Theoretical and Structural Chemistry, Pomorska 163/165, 09-236 Łódź.

5 Faculty of Pharmacy and Biochemistry, University of Zagreb, Ante Kovacica 1. Zagreb, Croatia.

In compare to ferrocenes, cymantrene and cyrhetrene derivatives have been far less explored

within bioorganometallic chemistry. In addition, bioorganometallics showing antiparasite activity are relatively neglected in contrast to widely explored anticancer active complexes. In this work we present the synthesis and characterization of the cymantrene and cyrhetrene nucleobase conjugates, and the evaluation of their activity against Trypanosoma brucei protozoa parasite [1]. T. brucei is a causative of African Trypanosomiasis (sleeping sickness) - a disease which occurs mainly in Sub-Saharan African countries. The key step in synthesis of our compounds involved an N1-regioselective Michael addition of the respective nucleobase nucleophile to an in situ generated organometallic acryloyl electrophile reagent. The mechanism of this reaction was examined by DFT calculations. The trypanocidal activity was evaluated in vitro with T. brucei bloodstream forms 427-221a. Majority of compounds showed a dose-dependent effect on the growth of trypanosomes with MIC values varying between 10 and >100 μM and GI50 values ranging from 0.38 to 80.5 μM. The majority of compounds showed no cytotoxicity against human HL-60 cancer cells what is a desirable effect.

Scheme 1. General structure of assayed compounds.

Acknowledgment K.K. thanks the National Science Centre in Cracow, Poland (Grant No. DEC-2013/11/B/ST5/00997 for financial support. References [1] K. Kowalski, Ł. Szczupak, S. Saloman, D. Steverding, A. Jabłoński, V. Vrcek, A. Hildebrandt,

H. Lang, A. Rybarczyk-Pirek ChemPlusChem., 2016, DOI:10.1002/cplu.201600462.

P-004

Synthesis, Antibacterial Activity and Mechanism of Action of Ruthenocenyl Cephalosporins

Konrad Kowalski1, Jolanta Solecka2, Yu Chen3, Eric Lewandowski3, Joanna Skiba1, Łukasz Szczupak1

1 Faculty of Chemistry, Department of Organic Chemistry, University of Łódź, Tamka 12, 91-403 Łódź, Poland.

2 National Institute of Public Health-National Institute of Hygiene, Chocimska 24, 00-791 Warsaw, Poland.

3 Department of Molecular Medicine, University of South Florida, Tampa, Florida 33612, United States.

A series of ruthenocenyl 7-aminodesacetoxycephalosporanic acid (7-ADCA) conjugates were

obtained. The antibacterial properties of these compounds have been tested against Gram+ methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA) and clinically isolated Staphyloccocus strains. We next set out to obtain a crystal structure of Ru-1 in complex with CTX-M E166A β-lactamase in an effort to gain insight into the molecular mechanism of action of the ruthenocenyl 7-ADCA derivative. The X-ray crystal structure revealed the acyl-enzyme complex (Figure 1) which is a key for antibacterial activity of all β-lactam antibiotics. Our combined synthetic, microbiological and crystallographic studies enable to understand us how organometallic compounds interact and inhibit pharmacologically crucial bacterial enzymes [1,2].

N

NH

O

Ru

O

S

COOHCH3

O

Ru-1   Figure 1. Covalent linkage of Ru-1 to Ser70 in the active site of CTX-M E166A β-lactamase.

Acknowledgment K.K. thanks the National Science Centre in Cracow, Poland (Grant No. DEC-2013/11/B/ST5/00997 for financial support. References [1] E.M. Lewandowski, J. Skiba, N.J. Torelli, A. Rajnisz, J. Solecka, K. Kowalski, Y. Chen,

Chem.Commun., 2015, 51, 6186-6189. [2] Manuscript in preparation.

P-005

Ultrasounds assisted Friedel-Crafts/Bradsher reaction: First use of ultrasounds in electrophilic aromatic cyclisation leading to polyacenes

Emilia Kowalska1, Piotr Bałczewski1,2, Joanna Skalik1, Agnieszka Bodzioch1 1 Group of Synthesis of Functional Materials, Department of Heteroorganic Chemistry, Centre of Molecular

and Macromolecular Studies, Polish Academy of Science, Sienkiewicza 112, 90-363 Łódź, Poland. 2 Department of Structural and Material Research, Institute of Chemistry, Environmental Protection and

Biotechnology, The Faculty of Mathematics and Natural Sciences, Jan Dlugosz Univeristy in Częstochowa, Armii Krajowej 13/15, 42-201 Częstochowa, Poland. pbalczew@cbmm.lodz.pl, kowalska@cbmm.lodz.pl

The main aim of our research was investigation of the ultrasounds effect on the intramolecular

cyclisation reaction of ortho-formyldiarylmethanes I and ortho-acetaldiarylmethanethers II, known as the Bradsher/Friedel Crafts reaction (Scheme 1). In this reaction, for the first time was used the unconventional source of energy which are ultrasounds and homogenic water-solvent systems. Optimization of the reaction conditions (selection of acidic catalyst, temperature, type of water-solvent system and parameters of ultrasounds) allowed to obtain new fused polycyclic (hetero)aromatic hydrocarbons containing or not containing alkoxy groups, respectively in III and IV. Application of ultrasounds in this reaction significantly shortened the reaction times compared to conventional methods without ultrasounds.[1] The obtained new cyclic compounds III and IV due to their specific properties may be used in various fields, such as optoelectronics (organic light emitting devices, organic field-effect transistors, photovolatics cells) or medicine (DNA intercalators, biologically active compounds).

 Scheme 1. Ultrasounds assisted Friedel Crafts/Bradsher cyclisation of I and II.

Acknowledgment The scientific work was financed from the Science Resources (National Science Centre – Poland) as research grants UMO-2012/07/M/ST5/01985 and UMO-2013/11/B/ST5/01610. References [1] E. Kowalska, P. Bałczewski, Ultrasonics Sonochemistry, 2017, 34, 743-753.

P-006

Synthesis and anticancer activity of hexacarbonyl dicobalt 5-alkynyl-2'-deoxyuridines

Renata Kaczmarek1, Dariusz Korczyński1, Karolina Królewska1, Roman Dembinski1,2 1 Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy

of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland. 2 Oakland University, Department of Chemistry, 146 Library Dr., Rochester, Michigan 48309-4479, USA.

The development of the synthesis of modified nucleosides is an important aspect of modern

drug discovery and biochemical research. Bioorganometallic chemistry has been introduced as a new way to improve the efficiency of active molecules. Cytotoxic nucleoside analogues were among the first chemotherapeutic agents to be introduced for the medical treatment of cancer. This family of compounds has grown to include a variety of purine and pyrimidine nucleoside derivatives with activity in both solid tumors and hematological malignancies. These agents behave as antimetabolites, compete with physiologic nucleosides, and consequently, interact with a large number of intracellular targets to induce cytotoxicity.[1] Potent biological properties have arisen by substitution at the 5-position of the uracil base.

In this communication we present the studies of new metallo-modified nucleosides using a methodology based on 5-substituted 2'-deoxyuridine skeleton and their hexacarbonyl dicobalt complexes.[2] Starting with 5-iodo-2'-deoxyuridine (1), a series of 5-alkynyl-2'-deoxyuridines (2a-d) has been synthesized via palladium-catalyzed Sonogashira coupling reaction. Reactions of 2a-d with Co2(CO)8 in THF gave dicobalt hexacarbonyl complexes (3a-d). The antitumor properties of the obtained compounds has been tested. The obtained complexes have been examined for their in vitro antiproliferative activity against HeLa (human cervix carcinoma) and K562 (leukemia) cell lines.

R= a) CH2OMe, b) CH2OAc c) CH2OH, d) C(OH)Me2

References [1] (a) Herdewijn, P. Modified Nucleosides in Biochemistry, Biotechnology and Medicine, Wiley-

VCH, Weinheim, 2008. (b) Deoxynucleoside Analogs in Cancer Therapy, Godefridus, J. P., Ed.; Humana Press, Totowa, 2006. (c) Chemical Synthesis of Nucleoside Analogues, Merino, P. Ed.; Wiley, 2013.

[2] Sergeant, C.D.; Ott, I.; Sniady, A.; Meneni, S.; Gust, R.; Rheingold, A.L.; Dembinski, R. Org. Biomol. Chem., 2008, 6, 73–80.

C C RHN

N

O

O

HO

OH

O

HN

N

O

O

HO

OH

OR

Co(CO)3Co

IHN

N

O

O

HO

OH

O

2a-e

Co2(CO)8

3a-e

(CO)3

1

THFCuI, Pd(PPh3)4Et3N, DMF

C C RH

P-007

Water-soluble, Heteroorganic Dendrimers Grzegorz M. Salamończyk1

1 Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź.

gmsalamo@cbmm.lodz.pl

Dendrimers [1] have created a remarkable interest, in areas ranging from materials science to

biomedical applications. These macromolecules exhibit a high density of surface functional groups that can be easily tuned according to the field of application. Charged dendrimers are generally water-soluble compounds useful for biomedical applications, and polyanionic dendrimers are proven to be less toxic than polycationic ones. Probably, the most important feature of polyanionic dendrimers is their significant antiviral activity, so they may serve as microbicidal drugs in their own right.[2] Antiviral dendrimers acting as non-natural imitations of the target cell surface are commonly designed with anionic surface groups.

In this communication, simple, and very efficient synthesis of water-soluble, polyanionic dendrimeric polyesters with different size, polarity, and flexibility is described. These macromolecular compounds consisting of phosphate or thiophosphate ester units and 1,3,5-benzenetricarboxylic acid building blocks may find potential applications as pharmaceutical agents. Synthesized the title polyanionic dendrimers possess charged carboxyl functional groups on the surface and were obtained, in high yields, from previously prepared series of new phosphorus-based dendrimeric polyols. The key monomers applied in this project were 1,3,5-benzenetricarboxylic acid di-tert-butyl ester and 1,3,5-benzenetricarboxylic acid bis(2,4-dimethoxybenzyl) ester. Both worked as the essential precursors of the dendrimer polyanionic surface. References [1] (a) Caminade, A.-M.; Turrin, C.-O.; Laurent R.; Ouali A. Dendrimers: Towards Catalytic,

Material and Biomedical Uses, Wiley 2011. (b) Campagna, S; Ceroni, P.; Puntorie, F. Designing Dendrimers, Wiley 2011.

[2] (a) McCarthy, T. D.; Karellas, P.; Henderson, S. A.; Giannis, M.; O’Keefe, D. F.; Heery, G.; Paull, J. R. A.; Matthews, B. R.; Holan, G. Mol. Pharm. 2005, 2, 312-318. (b) Rojo, J.; Delgado, R. Anti-Infective Agents 2007, 6, 151-174. (c) Jimenez, J. L.; Pion, M.; de la Mata, F. J.; Gomez, R.; Muñoz, E.; Leal, M.; Muñoz-Fernandez, M. A. New J. Chem. 2012, 36, 299-309.

P-008

In search of the ground state of dimethyl β-cyclodextrin Anna Ignaczak1, Łukasz Orszański1, Marta Adamiak1

1 Department of Theoretical and Structural Chemistry, Faculty of Chemistry, University of Lódź, Pomorska 163/165, 90-236 Lodz, Poland.

anignacz@uni.lodz.pl

Heptakis(2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD) belongs to the group of methyl

derivatives of β-cyclodextrin (β-CD). These compounds have the ability to form inclusion complexes with other molecules, therefore can be used as drug carriers. In comparison with the β-CD, its derivative DM-β-CD has a much greater solubility in water, what can increase the bioavailability of the drug. So far the properties of DM-β-CD were investigated primarily by experimental methods for crystal structures [1-3]. In order to determine the ground state of DM-β-CD in vacuo and in water we carried out conformational analysis of the molecule by a variety of theoretical methods, including semiempirical PM6, PM7 and the density functional B3LYP-GD2/6-31G(d,p). Additionally five selected experimental structures were examined with these methods. To evaluate an effect of the Grimme dispersion corrections and inclusion of diffuse functions on the results, for several lowest energy conformations obtained from the B3LYP-GD2/6-31G(d,p) optimizations we performed also single point calculations with the B3LYP-GD3, M062X-GD3, mPW1PW91 methods and the basis set 6-31++G(d,p).

In the poster it is shown that the results depend highly on the method used. The M062X-GD3/6-31++G(d,p) results suggest that the most stable structures are:

in vacuo in water (PCM)

     References [1] T. Steiner et al., Carbohydr. Res. 1995, 275, 73-82. [2] T. Aree et al., Carbohydr. Res. 1999, 315, 199-205. [3] J. J. Stezowski et al., J. Am. Chem. Soc. 2001, 123, 3919-3926.

P-009

Thiosemicarbazones as an important anticancer agents – synthesis and characterization of novel compounds

Marta Rejmund1, Jarosław Polański1 1University of Silesia in Katowice, Institute of Chemistry, Department of Organic Chemistry,

University of Silesia, Szkolna 9, 40-007 Katowice, Poland.

Thiosemicarbazones (TSC) are one of the most important class of organic compound with

great pharmaceutical value. The first reports about the thiosemicarbazones appeared at the beginning of the last century. In 1946 Domagk described antimycobacterial properties of aromatic aldehydes thiosemicarbazone, especially Conteben (TBI) – 4-acetylaminobenzaldehyde thiosemicarbazone. Clinical TBI administration of people began in Germany in 1947. Administering to patients suffering from various forms of pulmonary tuberculosis and extra-pulmonary areas [1,2].

TSCs exhibits a wide range of medical applications which include antibacterial, antiviral and antifungal activities. Some of them could be used as antitubercular drug and for the treatment of malaria. One of the most promising areas in which thiosemicarbazone compounds are being developed is their use against cancer. Their antitumor activity is extremely differentiated and it is very much dependent on the typology of tumour cells. Corresponding all of the biological properties of thiosemicarbazones, it is important to be able to synthesize new series of TSC which shows biological activities without any side effects [3,4].

In the structures of TSC there are sulfur and nitrogen donor atoms used by chelation of metal - especially transition metal ions. The presence of multiple donor atoms within the same ligand multiplying coordination modes and affects the properties of ligand and complexes [5].

Microwave – assisted synthesis of TSC allows to obtained pure products in high yields, minimize to use of organic solvents and shorter reaction times [3].

In result, eight thiosemicarbazides were prepared using a reflux method (2h under reflux in ethanol). Eight thiosemicarbazones were synthesized using a microwave – assisted methodology, all of them are novel compounds. The thiosemicarbazides and thiosemicarbazones were fully characterized by 1H- and 13C-NMR spectroscopy, TSC were characterized also by HMQC and COSY spectroscopic method. The structures of the received thiosemicarbazones were confirmed by using Liquid Chromatography - Mass Spectrometry. The examination for biological activity of these compunds is in progress. References [1] T. Urbański, C. Bełżecki, B. Chechelska i in., Gruźlica, 1958, 11/58, 892. [2] E. Costeletos, F. Gerocostopoulos, A. Chronopoulos, Pulmonary Tuberculosis, 1954, XXV,

580-584. [3] C. Moretto dos Reis, D. Sousa Pereira, R. Paiva, L. Ferreira Kneipp, A. Echevarria, Molecules,

2011, 16, 10668-10684. [4] D.S. Kalinowski, D.R. Richardson, Pharm. Rev., 2005, 57, 575-577. [5] J. L. Bautista, M. Flores-Alamo, J. Tiburcio, R. Vieto, H. Torrens, Molecules, 2013, 18,

13111-13123.

P-010

Phyto- and Ecotoxicological Properties of C-Aryl and Heteroaryl Derivatives of Phosphonoglycine

Jarosław Lewkowski1, Rafał Karpowicz1, Marta Morawska1, Piotr Rychter2, Diana Rogacz2, Kamila Lewicka2

1 Department of Organic Chemistry, Faculty of Chemistry, University of Łódź, Tamka 12, 91-403 Łódź, Poland.

2 Institute of Chemistry, Environmental Protection and Biotechnology, Jan Długosz University in Częstochowa, 42-200 Częstochowa, 13/15 Armii Krajowej Av., Poland.

Series of unknown, various C-aryl, heteroaryl and C-metallocenyl substituted derivatives of phosphonoglycine (1-4) have been synthesized via modified aza-Pudovik or Kabachnik-Fields reactions. It is to stress that aminophosphonates derived from 5-nitrofurfural have not been described before.

Some aspects of the toxicological impact on terrestrial higher plants of the investigated aminophosphonates 3 have been reported by us [1, 2] and in this communication, we will discuss phytotoxicity of other compounds of study 1, 2 and 4.

Considering that known compounds applied in herbicidal formulations show important ecotoxicity [3], we performed ecotoxicological tests and we will present results of action of compounds 1-4 on fluorescent bacteria Vibrio fischeri and crustaceans Heterocypris incogruens.

NH

PO3(R2)2

HN R1S

PO3(R2)2

HN R1O

PO3(R2)2

HN R1O2N

Fe

PO3(R2)2

HN R1

R1 = CH3, CH2CH3, CH2Ph, Ph R2 = o-, m-, p-CH3, o-, m-, p-OCH3

1 2 3 4

Scheme 1. Groups of derivatives investigated in the project.

Acknowledgment The financial support of the NCN, grant no. 2014/13/B/NZ9/02418 is kindly acknowledged. References [1] A. Matusiak, J. Lewkowski, P. Rychter, R. Biczak, J. Agric. Food Chem., 2013, 61(32),

7673–7678. [2] J. Lewkowski, Z. Malinowski, A. Matusiak, M. Morawska, D. Rogacz, P. Rychter,

Molecules 2016, 21, 694 [3] B. Pawłowska, R. Biczak, Chemosphere, 2016, 149, 24-33.

P-011 

Efficient and Stereoselective Synthesis of Unique Polycyclic -Lactams with Benzomorphan Skeleton Tomasz J. Idzik1, Łukasz Struk1, Jacek G. Sośnicki1

1 West Pomeranian University of Technology, Department of Organic and Physical Chemistry, Al. Piastów 42, Szczecin 71-065, Poland.

Polycyclic organic compounds with piperidine core are widespread in naturally

occurring alkaloids and in biologically active compounds. Probably the best known examples are analgetic codeine and morphine. These structurally complex alkaloids have become the prototypes of simpler compounds – benzomorphans,[1] which exhibited improved analgetic and other therapeutic activities. Although -lactams have been widely used as synthetic precursors of functionalized piperidines, the synthesis of compounds based on benzomorphan skeleton from -lactams has not been a popular research subject. Recently, only -unsaturated -lactams have been used in the syntheses of benzomorphanones.[2]

As a continuation of our ongoing program aimed at the synthesis of functionalized piperidine derivatives, achieved from readily available starting materials,[3] in this communication we present the efficient and stereoselective synthesis of unique tetracyclic -lactams 4, which can be regarded as bridged benzomorphan derivatives (Scheme 1). In their synthesis -unsaturated -lactams 2 were used as starting material, which in turn were simply obtained from 2-pyridones 1.[4] The key steps comprised halocarbocyclization of 2 and intramolecular cyclopropane ring formation in 3.

Scheme 1. References [1] D. C. Palmer, M. J. Strauss, Chem. Rev., 1977, 77, 1-36. [2] Q. Chen, X. Huo, H, Zheng, X. She, Synlett 2012, 1349-1352; B. Fang, H. Zheng, C. Zhao,

P. Jing, H. Li, X. Xie, X. She, J. Org. Chem., 2012, 77, 8367−8373. [3] J. G. Sośnicki, P. Dzitkowski, Ł. Struk, Eur. J. Org. Chem. 2015, 5189–5198 and references

cited therein. [4] J. G. Sośnicki, T. J. Idzik, A. Borzyszkowska, E. Wróblewski, G. Maciejewska, Ł. Struk,

Tetrahedron. 2016 submitted.

P-012 

Non-pericyclic nature of thermal decomposition of nitroethyl carboxylates

Agnieszka Kącka1, Radomir Jasiński1 1 Department of Organic Chemistry, Cracov University of Technology,

Warszawska Street 24, 31-155 Cracov, Poland. akacka@chemia.pk.edu.pl

Conjugated nitroalkenes (CNA) are very valuable precursors in organic synthesis

because of their easy conversion to a variety of diverse intermediates, biological and pharmaceutical properties. There are many methods for preparation of nitroalkenes, however the most common involves a decomposition of nitroalkyl esters. Although some of the decomposition reactions for preparation nitroalkenes are efficient, but they are provide in strict reaction conditions, are expensive and lead with low yield to nitroalkenes. Therefore, research aimed at searching relatively mild conditions for universal methodology for preparation of CNA are justified.

Due to above issues, we have performed DFT study of thermal decomposition reactions of nitroethyl carboxylates. In particular, we have carry out simulations of reaction paths for processes involving substituents with various donor-acceptor power in the phenyl ring [1,2]. We analyzed these reactions at various theory levels and in the presence of medium with different polarity.

Scheme 1. Thermal decomposition reaction of nitroethyl carboxylates.

References [1] A. Kącka, R. Jasiński, Heteroatom Chem., 2016, 27, 279-289. [2] R. Jasiński, A. Kącka, J. Mol. Model., 2015, 21, 59-65.

P-013 

Understanding of unexpected, extremely low reactivity of (2E)-3-[4-(dimethylamino)phenyl]-2-nitroprop-2-enenitrile

Radomir Jasiński1, Barbara Mirosław2, Oleg M. Demchuk3, Dmytro Babyuk4, Agnieszka Łapczuk-Krygier1

1 Cracow University of Technology, Institute of Organic Chemistry and Technology, Cracow, Poland. radomir@chemia.pk.edu.pl

2A Maria Curie-Sklodowska University, Department of Crystallography, Lublin, Poland. 3 Maria Curie-Sklodowska University, Department of Organic Chemistry, Lublin, Poland.

4 Chernivtsi National University, Institute of Biology, Chemistry and Bioresourses, Chernivtsi, Ukraine.

(2E)-3-[4-(dimethylamino)phenyl]-2-nitroprop-2-enenitrile 1 has got extremely low reactivity in regard to other similar derivatives. In this study we try explain this property. The molecular structure of the title compound 1 has been studied by experimental and theoretical methods. The crystal structure analysis provided the evidence, that the title compound exists in a solid state as a stable E-isomer in a zwitterionic form. Based on NMR, IR, UV/VIS spectroscopic and DFT calculations data, this structure has been also proposed for 1 dissolved in organic solvents. (2E)-3-[4-(dimethylamino)phenyl]-2-nitroprop-2-enenitrile is the only compound in the group of (2E)-3-aryl-2-nitroprop-2-enenitriles in which the theoretically predicted zwitterionic form has been confirmed by the full experimental study. The molecular structure of the title compound fulfills the requirements for being a π-conjugated “push-pull” molecule [1], where the –N(CH3)2 and –NO2 functional groups arranged linearly may act as an electron-donor and an electron-acceptor, respectively, transferring the charge through the styrene π system [2]. Such zwitterionic nature of 1 could explain the surprisingly low reactivity of this compound.

NaOH- H+ - H2O

HCl

SOCl2C3H7NH2

- HCl- SO2

- H2O

1 Scheme 1. Synthetic route to (2E)-3-[4-(dimethylamino)phenyl]-2-nitroprop-2-enenitrile (1).

References [1] F. Bures, RSC Adv. 4 (2014) 4, 58826. [2] V.K. Gupta, R.A. Singh RSC Adv. 5 (2015) 38591.

P-014 

Diazafluorene as 1,3-dipole in reactions with conjugated nitroalkenes

Karolina Kula1, Agnieszka Kącka1, Barbara Mirosław2, Radomir Jasiński1 1 Cracow University of Technology, Institute of Organic Chemistry and Technology, Warszawska 24,

31-155 Cracow, Poland. radomir@chemia.pk.edu.pl 2 Maria Curie-Skłodowska University, Department of Crystallography, Maria Curie-Skłodowska 3,

20-031 Lublin, Poland.

Conjugated nitroalkenes (CNA) allow for the synthesis several interesting compounds,

for example nitronic acid esters, amines, oximes and many other [1]. CNA have a highly electron–withdrawing nitro group, which are stimulate π – deficiency of a double bond. In consequence, this effect which activates these compounds in stereocontrolled reaction with nucleophilic reagents such as dienes, 1,3-dipoles and etc [2].

The reaction between alkenes and diazafluorene as 1,3-dipole are known from the beginning of 20th century [4]. On this way ∆1–pirazoline systems are formed. These reactions proceed under mild conditions giving high yields of cycloadducts. Obtained compounds have interesting applications in medicinal chemistry [3-5].

In present work, we can be prepared nitrofunctionalyzed pirazoline systems via 1,3-dipolar cycloadditions between diazafluorene and homogenous series of (E)-2-aryl-1-cyano-1-nitroethenes. It was found, that, by the reaction it possible to create two regioisomeric adducts presented of scheme 1. Additionally to experimental study, we have performed DFT simulation of reactions potential energy surface.

NN

NO2CN

R

NN

CN

NO2

R

N+

N

CC

NO2NC

H

R

-

+

Scheme 1. Theoretically possible paths of reaction between diazafluorene

and (E)-2-aryl-1-cyano-1-nitroethenes References [1] N. Ono, The Nitro Group in Organic Synthesis, 2001, Wiley-VCH, Weinheim. [2] R. Jasiński, Reakcje 1,3-dipolarnej cykloaddycji: aspekty mechanistyczne i zastosowane

w syntezie organicznej, 2015, RTN, Radom. [3] H. Staudinger, A. Gaule, Chem. Ber., 1916, 49, 1959. [4] M. Vasin, S. Razin, Russ. J. Organ. Chem., 2014, 50, 1323-1334. [5] G., Mlostoń, K. Urbaniak, A. Linden, H. Heimgartner, Tetrahedron Lett., 2009, 65,

8191-8196.

P-015 

Crystal structure analysis of optically active t-butylarylphosphinothioic and t-butylarylphosphinoselenoic

acids - new chiral solvating agents (CSAs) Grażyna Mielniczak1, Jarosław Błaszczyk1, Lesław Sieroń2,

Patrycja Pokora-Sobczak1, Marian Mikołajczyk1, Józef Drabowicz1 1 Centre of Molecular and Macromolecular Studies of Polish Academy of Sciences, Department of

Heteroorganic Chemistry, Sienkiewicza 112, 90-363 Lodz, Poland. 2 Technical University of Lodz, Institute of General and Ecological Chemistry, Żeromskiego 116,

90-924 Lodz, Poland.

The increasing tendency to use drugs as single enantiomers and progress in

enantioselective synthesis have stimulated the investigation of methods for determination of enantiomeric purity and absolute configurations of chiral compounds.[1] The best results have been obtained using the NMR method based on the use of CSAs.[2] Since 1978, an optically active t-butylphenylphosphinothioic acid has been most often applied as CSA for determination of the enantiomeric excess of chiral compounds.[3,4] Recently, we have synthesized the new, optically active, members of a family of t-butylarylphosphinothioic (1a-c) and t-butylarylphosphinoselenoic acids (2a, b), and utilized them as new chiral solvating agents in NMR spectroscopy (Scheme 1).

We will present our first results of X-ray structure determination of our newly synthesized series of thio- (1) and selenophosphinic acids (2) (Scheme 1, compounds (-)-S-1a and (+)-R-2a). For (-)-1a, the absolute configuration at the phosphorus atom is (S). The asymmetric unit contains two independent molecules which differ in the conformation of methoxy group (see Figure 1). Compounds (-)-S-1a (final R=1.74%) and (+)-R-2a (final R=1.50%) are isostructural, with similar systems of intermolecular interactions P-O-H•••S(Se) and π-π. The exception is only the opposite absolute configuration at the phosphorus atom. Both structures of (-)-S-1a and (+)-R-2a have been deposited at the Cambridge Structural Database, with the respective codes: CCDC 1509139 and 1509140.

tBuP

Ar

S

OH1 a-c

Ar: a: p-MeOC6H4 b: p-CF3C6H4 c: Nph

tBuP

Ar

Se

OH2 a, b

(-) and (+) (-) and (+)                     

Scheme 1 Figure 1 Acknowledgment The authors thank for the support from the fund of the National Science Center awarded on the basis of the decisions UMO-2015/17/N/ST5/03908. References [1] D. Parker, Chem. Rev., 1991, 91, 1441-1457. [2] W. H. Pirkle, J. Am. Chem. Soc., 1966, 88, 1837. [3] M. J. P. Harger, J. Am. Chem. Soc. Perkin II, 1973, 326-331. [4] J. Drabowicz, et al., Phosphorus Sulfur Silicon Relat. Elem., 2014, 189, 977-999.

P-016 

Synthesis of isothiocyanates using nosyl chloride as desulfurating agent

Maciej Saktura1, Łukasz Janczewski1, Anna Gajda1, Tadeusz Gajda1* 1 Institute of Organic Chemistry, Lodz University of Technology, Żeromskiego 116 St.,

90-924 Łódź, Poland.

Natural isothiocyanates (ITC) are important class of biologically active

heterocummulenes. They are non-toxic and they selectively inhibit the growth of tumor cells in vivo and induce their apoptosis. [1] They occur in cruciferous vegetables, including brussels sprout, broccoli, cauliflower or wasabi as glucosinolates, which through the action of myrosinase are converted to active isothiocyanates. ITC are also useful substrates in the synthesis of heterocyclic compounds. [2]

  

The aim of this project was to develop the method of synthesis of structurally diverse ITC from primary amines or their salts using nosyl chloride (NsCl) as a desulfurating agent of the intermediate ditiocarbamates formed in this transformation and compare this method with reaction, in which tosyl chloride was used as a desulfurating agent. [3] Acknowledgment The authors gratefully acknowledge financial support from the Lodz University of Technology DS./I-18/2015. References [1] S. L.Navarro, F. Li, J. W. Lampe, Food Funct., 2011, 2, 579. [2] A. K. Mukerjee, R. Ashare, Chem. Rev., 1991, 91, 1. [3] R. Wong, S. J. Dolman, J. Org. Chem., 2007, 72, 3969.

P-017 

Chiral aziridine ligands in asymmetric addition of arylzinc reagents to aldehydes

Zuzanna Wujkowska1, Michał Rachwalski1, Stanisław Leśniak1, Szymon Jarzyński1 1A University of Łódź, Faculty of Chemistry, Department of Organic and Applied Chemistry,

Tamka 12, 91-403 Łódź, Poland. zuzanna.wujkowska@gmail.com

Asymmetric catalysis represents one of the most important research fields of modern

organic chemistry due to the high importance of optically pure compounds in many industrial sectors [1]. As a continuation of our interest in the field of stereocontrolled synthesis, we have decided to extend the scope of applicability of the previously synthesized chiral aziridine alcohols using them as chiral ligands in the asymmetric addition of arylzinc reagents to aldehydes. The products were formed in high chemical yields and with high enantiomeric excess.

I

OMe

I

MeO2C

1. Et2Zn, Li(acac), NMP, 0 oC, 12 h2. Ligand (20 mol%), THF, 0 oC, 1h3. RCHO, rt

OMe

MeO2C

R

R

OH

OHR = 4-MeC6H4R = 4-ClC6H4R = i-Pr R = Cy

B(OH)21. ZnEt2, toluene, 60 oC, 15 min.2. Ligand (10 mol%), toluene, rt, 15 min.3. Aldehyde, rt, 24 h Ar

OH

Ar = 4-ClC6H4Ar = 4-MeOC6H4 Ar = 2-MeOC6H4 Ar = 4-BrC6H4

References [1] M. Rachwalski, N. Vermue, F. P. J. T. Rutjes, Chem. Soc. Rev. 2013, 42, 9268-9282.

P-018 

FTIR ATR spectroscopy of polymer film of Ni(II) complex with derivative of salen containing cyclohexane moiety in amine bridge Danuta Tomczyk1, Wiktor Bukowski2, Karol Bester2, Paweł Urbaniak1, Piotr Seliger1,

Sławomira Skrzypek1 1 Uniwersytet Łódzki, Katedra Chemii Nieorganicznej i Analitycznej, ul. Tamka 12,

91-403 Łódź, Poland. 2 Politechnika Rzeszowska, Katedra Technologii i Materiałoznawstwa Chemicznego,

Al. Powstańców W-wy 6, 35-959 Rzeszów, Poland.

Ni(II) complexes with Schiff base-type N2O2 are used in many areas of chemistry. Due to

the possibility of anodic electropolymerization, the modification of the electrodes by complexes of the ligands with the free ortho and para positions in phenolate moieties are of particular importance. Such modified electrodes are used in the anode and cathode heterogeneous electrocatalysis [1] as well as in electroanalysis.

The obtained by anodic electropolymerization polymer complex of (±)-trans-N,N'-bis (salicylidene)-1,2-cyclohexanediaminanickel(II), [Ni (salcn)] has been investigated.

The process involves recording a certain number of cyclic voltammetric curves within the positive potentials ranges (0÷1.6 or 0÷2.1 V) on the platinum electrode in 10-3 mol/dm3 solution of [Ni (salcn)] in CH2Cl2 containing 10-1 mol/dm3 Bu4NPF6 or Bu4NClO4. As a result of this process, on the electrode surface, the yellow polymer films insoluble in the solvent was obtained.

The presented studies show the analysis of electropolymerization mechanism on the basis of the results of FTIR spectroscopy of the complex and FTIR (ATR) of the polymer films deposited on the electrode surface.

It was found that electropolymerization occurs through phenyl-phenyl type bonds. An increased intensity of the bands corresponding to υ C-C on the aromatic ring (1600/1545

cm-1) of the polymer relative to the ratio in the complex and the additional band (1560(m)) for polymer in this range indicate a conjugated system of aromatic rings in the polymer.

In contrast, the same intensity of the bands corresponding to υ C=N in the complex and in the film, and few differing intensity of the bands corresponding to the δ CH2 in the complex and in the film indicate the location of these groups outside the coupling area. The vibration intensity of the groups not involved in the coupling is limited to a much lesser extent than vibration of conjugated groups.

Band shift in the range of δ CH (680-900 cm-1), characteristic for the way of aromatic substitution within the ring, indicates the change in substitution from the ortho- observed in sole complex (750(s)) to tetrasubstituted aromatic ring in the polymer species (892 (m)).

The change in substitution type of the ring is also confirmed by a change of overtones (1667 2000 cm-1).

Based on FTIR studies of the complex, and FTIR (ATR) of the polymer it was found that electropolymerization occurs by phenyl-phenyl bonds, in both active directions, ortho- and para-. References [1] E.R. Wagoner, C.P. Baumberger, B.H.R. Gerroll, D.G. Peters, Electrochim. Acta, 2014,

132, 545-554.

P-019 

Fungicidal activity of new conjugates: 10-alkylthiocolchicines-aspirin and 7-deacetyl-10-alkylthiocolchicines-aspirin

Joanna Kurek1, Patrycja Kwaśniewska-Sip2, Grzegorz Cofta2, Piotr Barczyński1 1 Faculty of Chemistry, A. Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland.

2 Institute of Chemical Wood Technology, University of Life Science, Wojska Polskiego 38/42, 60-037 Poznań, Poland.

joankur@amu.edu.pl, kwasniewskapatrycja@gmail.com

Colchicine 1 is a well known traditional bio-active alkaloid, naturally occurring in plants

of the Liliaceae family especially in meadow saffron (Colchicum autumnale), whose antimitotic activity has been mainly applied for acute gout therapy. Because of its toxicity, its molecular structure had to be modified for medical purposes. Semi-synthetic C-10 alkylthioated analogues have been found to exhibit cytotoxicity towards tumour cell lines at levels comparable to that of the natural product or even more toxic [1]. 10-Alkylthiocolchicine derivatives 2-6 were mixed with aspirin 12 and also 7-deacetyl-10-alkylthiocolchicines 7-11 were mixed with aspirin 12 to gave conjugates 13-24. 10-alkylthiocolchicines and 7-deacetyl-10-alkylthiocolchicines and their conjugates with aspirin were tested against fungicidal activity.

 Scheme 1. Structure of colchicine 1, 10-alkylthiocolchicines and 7-deacetyl-10-alkylthiocolchicines.

The 96-well microtiter assay was used to determine the sensitivity of eight strains of microfungi commonly known as mould Aspergillus niger van Tiegen, Aspergillus versicolor (Vuill.) Tirab., Paecilomyces variotii Bainier, Penicillium funiculosum Thom, Chaetomium globosum Kunze, Aureobasidium pullulans (de Bary) G. Arnaud, Penicillium cyclopium Westling and Trichoderma viride Pers. to new obtained complexes. In this study the properties of 7-deacetyl-10-alkylthiocolchicine derivatives against microfungi were analysed and compared with those 10-alkylthiocolchicines which were completely inactive against all tested fungi species. The colchicine and 7-deacetyl-10-alkylthiocolchicine derivatives with aspirin showed very good fungistatic properties compared to all tested compounds. The results permit a conclusion that the antifungal properties of some new complexes of colchicine may be potentially useful for partly controlling moulds. References [1] J. Kurek, W. Boczoń, K. Myszkowski, M. Murias, T. Borowiak, I. Wolska, Letters in Drug

Design & Discovery, 2014, 11, 279-289. [2] J. Kurek, G. Bartkowiak, W. Jankowski, P. Kwaśniewska-Sip, G. Schroeder, M. Hoffmann,

G. Cofta, P. Barczyński, IOSR Journal of Pharmacy 2016, 6 (8), 40-55.

P-020 

Fungicidal activity of colchicine, colchiceine and 10-methylthiocolchicine complexes with Li+, Na+, K+, Rb+ and Cs+ Joanna Kurek1, Patrycja Kwaśniewska-Sip2, Grzegorz Cofta2, Piotr Barczyński1

1 Faculty of Chemistry, A. Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland. 2 Institute of Chemical Wood Technology, University of Life Science, Wojska Polskiego 38/42,

60-037 Poznań, Poland. joankur@amu.edu.pl, kwasniewskapatrycja@gmail.com

Colchicine (Scheme 1.) is a well known traditional bio-active alkaloid, naturally

occurring in plants of the Liliaceae family especially in meadow saffron (Colchicum autumnale), whose antimitotic activity has been mainly applied for acute gout therapy. Because of its toxicity, its molecular structure had to be modified for medical purposes. Colchicine is an alkaloid characterised by good water solubility. The colchicine 1, colchiceine 2 and 10-methylthiocolchicine 3 complexes with Li+, Na+, K+ of iodides and perchlorates have been synthesized and studied previously by spectral methods [1-2]. Colchicine complexes with sodium, potassium, magnesium and calcium sulphates and carbonates have been obtained and studied by spectral methods and also as against their fungicidal activity [3]. In the present work complexes of 1, 2 and 3 with Li+, Na+, K+, Rb+ and Cs+ perchlorates and iodides were synthesized and tested against their fungicidal activity.

OCH3

H3COH3CO

H3CO

O

HN

O

CH3A B

C

SCH3

H3COH3CO

H3CO

O

HNA B

C

1 2

O

3OH

H3COH3CO

H3CO

O

HN

O

CH3A B

C

Scheme 1. Structure of colchicine 1, colchiceine 2 and 10-methylthiocolchicine 3 molecules.

In this study the properties against microfungi were analyzed using the 96-well microtiter plate-based method to determination of effective alkaloid concentrations for 100% growth reduction (LD100). The microfungal strains used in the bioassay were Aspergillus niger van Tiegen, Aspergillus versicolor (Vuill.) Tirab., Paecilomyces variotii Bainier, Penicillium funiculosum Thom, Chaetomium globosum Kunze, Aureobasidium pullulans (de Bary) G. Arnaud, Penicillium cyclopium Westling, Trichoderma viride Pers. Among the new derivatives with antifungals properties the colchicine complexes with potassium iodide was the most potent agent. Additionally complexes of colchiceine showed better fungistatic activity than complexes of colchicine and 10-methylthiocolchicine. New derivatives of colchiceine were active against most fungal species used in the bioassay. References [1] J. Kurek, Wł. Boczoń, P. Przybylski and B. Brzeziński, J. Mol. Struct. 2007, 846, 13-22. [2] J. Kurek, P. Barczyński, Croatica Chemica Acta, 2016, 89, 3, in press. [3] J. Kurek, G. Bartkowiak, W. Jankowski, P. Kwaśniewska-Sip, G. Schroeder, M. Hoffmann,

G. Cofta, P. Barczyński, IOSR Journal of Pharmacy 2016, 6 (8), 40-55

P-021 

Human body fluid ions in colchicine complexes ESI MS, MADLI MS, spectroscopic, DFT studies and fungicidal activity

of colchicine complexes with sodium, potassium, magnesium and calcium carbonates and sulphates

Joanna Kurek1, Grażyna Bartkowiak1, Wojciech Jankowski1, Patrycja Kwaśniewska-Sip2, Grzegorz Schroeder1, Marcin Hoffmann1,

Grzegorz Cofta2, Piotr Barczyński1 1 Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland.

2 Institute of Chemical Wood Technology, University of Life Science, Wojska Polskiego 38/42, 60-037 Poznań, Poland.

joankur@amu.edu.pl

Colchicine (Scheme 1.) is an alkaloid characterised by good water solubility. After

administration of colchicine as a medicine for example for the treatment of gout, colchicine probably forms some more or less stable structures with cations and/or anions present in human body fluid. The colchicine complexes with Na+, K+ Mg2+ and Ca2+ cations of sulphates and carbonates have been synthesized and studied by ESI MS, MALDI MS, 1H and 13C NMR, FT IR DFT calculations and also have been tested against fungicidal activity. Salts of good solubility in water have been chosen, like Na2SO4, K2SO4, Na2CO3, K2CO3, MgSO4 and CaSO4. It has been shown that colchicine forms stable complexes of 1:1 stoichiometry with monovalent and divalent metal cations. For K+ and Na+ cations also formation of 2:1 stoichiometry complexes has been detected. Colchicine with sodium sulphate forms much more complicated structures of 1:2:1 and 2:2:1 stoichiometry in which sulphate anion is involved. Colchicine complexes have fungicidal activity.

OCH3

H3COH3CO

H3CO

O

HN

O

CH3A B

C

 Scheme 1. Structure of colchicine molecule.

In the present work it was found that colchicine can form stable complexes with ions of human body fluids like: Na+, K+, Ca2+ and Mg2+. Colchicine with sodium, potassium, magnesium and calcium sulfates and sodium, potassium carbonates can form much more complicated complexes in stoichiometry 2:1 and for complex with sodium sulphate 3:1 and 2:1:1. Moreover, sulphate anions were also involved in complexation process. Quantum-mechanical calculations helped indicate which colchicine atoms are involved in coordinating sodium cation. It appears that one colchicine molecule is particularly strongly bound to Na+ and interacts via O4, O1 and O2 oxygen atoms. New colchicine complexes show fungicidal activity against selected species of moulds, in the future they may be potentially useful for controlling the growth of fungi. References [1] J. Kurek, Wł. Boczoń, P. Przybylski and B. Brzeziński, J. Mol. Struct. 2007, 846, 13-22. [2] J. Kurek, G. Bartkowiak, W. Jankowski, P. Kwaśniewska-Sip, G. Schroeder, M.

Hoffmann, G. Cofta, P. Barczyński, IOSR Journal of Pharmacy 2016, 6 (8), 40-55.

P-022 

ESI MS mass spectra studies of 7-deacety-10-methylthiocolchicine complexes with lithium, sodium, potassium iodides and

perchlorates Joanna Kurek1, Barbara Stańska1, Piotr Barczyński1

1Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland. joankur@amu.edu.pl

Colchicine (Scheme 1.) is an alkaloid characterised by good water solubility. After

administration of colchicine as a medicine for example for the treatment of gout, colchicine probably Because of its toxicity, its molecular structure had to be modified for medical purposes. Colchicine is an alkaloid characterised by good water solubility. The colchicine 1, colchiceine 2 and 10-methylthiocolchicine 3 complexes with Li+, Na+, K+ of iodides and perchlorates have been synthesized and studied previously by spectral methods [1-2]. Colchicine complexes with sodium, potassium, magnesium and calcium sulphates and carbonates have been obtained and studied by spectral methods and also as against their fungicidal activity [3]. In the previous study in the ESI MS mass spectra it has been shown that colchicine forms stable complexes of 1:1 stoichiometry with monovalent and divalent metal cations. For complexes with K+ and Na+ cations also formation of 2:1 stoichiometry complexes has been detected. Colchicine with sodium sulphate forms much more complicated structures of 1:2:1 and 2:2:1 stoichiometry in which sulphate anion is involved. Colchicine complexes have fungicidal activity.

OCH3

H3COH3CO

H3CO

O

HN

O

CH3A B

C

SCH3

H3COH3CO

H3CO

O

NH2A B

C

1 2 

Scheme 1. Structure of colchicine 1 and 7-deacetyl-10-methylthiocolchicine 2 molecules. The aim of this study was to find out that colchicine derivatives have complexing capacity. In the present study a synthetic derivative of colchicine the 7-deacetyl-10-methylthiocolchicine 2 was obtained and its complexes 3-8 with with Li+, Na+, K+ of iodides and perchlorates were synthesized and studied by spectral methods: ESI MS, 1H and 13C NMR, FT IR. In the ESI MS mass spectra. In the ESI MS mass spectra 7-Deacetyl-10-methylthiocolchicine 2 with lithium, sodium and potassium can form complexes in stoichiometry 1:1 and 2:1, perchlorate or iodide anions were not involved in complexes formation. References [1] J. Kurek, Wł. Boczoń, P. Przybylski and B. Brzeziński, J. Mol. Struct. 2007, 846, 13-22. [2] J. Kurek, P. Barczyński, Croatica Chemica Acta, 2016, 89, 3, in press. [3] J. Kurek, G. Bartkowiak, W. Jankowski, P. Kwaśniewska-Sip, G. Schroeder, M. Hoffmann,

G. Cofta, P. Barczyński, IOSR Journal of Pharmacy 2016, 6 (8), 40-55.

P-023 

Synthesis of rhodanine-3-carboxyalkylic acid derivatives possessing antibacterial activity

Waldemar Tejchman1, Izabela Korona-Głowniak2, Ewa Żesławska1, Agnieszka Kania1, Iwona Stawoska1

1 Department of Chemistry, Institute of Biology, Pedagogical University of Cracow, ul. Podchorążych 2, 30-084 Kraków, Poland

2Department of Pharmaceutical Microbiology, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland

2-Thio-4-thiazolidinone (rhodanine) derivatives possess a broad range of biological

activity, among others antibacterial, antifungal [1], antiviral [2] and anticancer properties [3]. In comparison to their oxygen analogues (thiazolidin-2,4-diones), rhodanines generally show a higher antibacterial activity [4]. It has been also confirmed that this activity significantly depends on the substituent at C-5 position [5]. In order to investigate the influence of substituents at C-5 positions and the length of the linker between carboxyl group and nitrogem atom (N3) on the antibacterial activity of rhodanine-3-carboxyalkylic acids derivatives, synthesis of suitable compounds were curried out. The obtained derivatives contain a carboxyalkyl group at N-3 position of the rhodanine ring, wherein the alkyl group has from 1 to 3 carbon atoms. There are 4-(N,N-dialkyl/diaryl-amino)-benzylidene substituents at C-5 position. The chemical structures of the received compounds were confirmed using spectroscopic methods (IR, MS, 1H NMR, 13C NMR) and X-ray analysis. All synthesized compounds inhibit growth of Gram-positive bacteria, however, none of the tested derivatives have activity against Gram-negative bacteria. References [1] A. Insuasty, J. Ramírez, M. Raimondi, C. Echeverry, J. Quiroga, R. Abonia, M. Nogueras,

J. Cobo, M. V. Rodríguez, S. A. Zacchino, B. Insuasty, Molecules 2013, 18, 5482-5497. [2] K. Ramkumar, V.N. Yarovenko, A.S. Nikitina, I. V. Zavarzin, M.M. Krayushkin, L.V.

Kovalenko, A. Esqueda, S. Odde, N. Neamati, Molecules, 2010, 15, 3958-3992 [3] B.A. Rao, R.S. Raipoot, V.G.M. Naidu, K. Srinivas, S. Ramakrishna, V.J. Rao,

International Journal of Pharma and Bio Sciences 2011, 2, 191 – 202. [4] O. Zvarec, S.W. Polyak, W. Tieu, K. Kuan, H. Dai, D.S. Pedersen, R. Morona, L. Zhang,

G.W. Booker, A.D. Abell, Bioorg. Med. Chem. Lett. 2012, 22, 2720-2722. [5] R.T. Pardasani, P. Pardasani, S. Sherry, V. Chaturvedi, Ind. J. Chem., 2001, 40B,

1275–1278.

NR

RHOOC-(CH2)n

S

N

S

O

CHn = 1, 2 or 3R = C2H5, C4H9 or C6H5

P-024 

Ferrocenyl Nucleoside: Synthesis and Chemistry Iurii Anisimov1, Konrad Kowalski1

1Faculty of Chemistry, Department of Organic Chemistry, University of Łódź, Tamka 12, 91403 Łódź, Poland.

Ferrocenyl-nucleobases are an increasingly important class of compounds with possible

applications in biology and material sciences [1]. Poster focus on synthetic method for ferrocenyl nucleoside 1 and chemical transformations of this new canonic nucleoside mimic.

Compound 1 can potentially serve as redox-active artificial nucleic acid building block. Furthermore we are interested in biological activity of these classes of compounds. References [1] K. Kowalski, Coord. Chem. Rev., 2016, 317, 132-156.

P-025 

Synthesis and acid-promoted transformation of sterically crowded pyrenecarbothioamide S-oxides

Marzena Witalewska1, Anna Wrona-Piotrowicz1, Anna Makal2, Janusz Zakrzewski1 1 Department of Organic Chemistry, Faculty of Chemistry, University of Łódź, Tamka 12,

91-403 Łódź, Poland. 2 Department of Chemistry, Warsaw University, Pasteura 1, 02-093 Warsaw, Poland.

marzena-witalewska@o2.pl

Reaction of 2,7-di-tert-butylpyrene with N-ethoxycarbonyl isothiocyanate gave

sterically crowded thioamides 1,2[1]. Oxidation of these compounds with oxone® afforded the corresponding S-oxides 3, 4 in good yield.

 

Treatment of 3 with trifluoromethanesulfonic (triflic) acid in dichloromethane at room temperature resulted in formation of tiophene-fused pyrenes 5 and 6, whereas the similar treatment of 4 afforded bis-nitrile 7.

The mechanism of these transformations will be proposed. References [1] A. Wrona-Piotrowicz, J. Zakrzewski, R. Métivier, A. Brosseau, A. Makal, K. Woźniak, RSC

Advances, 2014, 4, 56003-12.

P-026 

Application of different theoretical methods to study azacrown ethers

Marta Adamiak1, Anna Ignaczak1 1 Department of Theoretical and Structural Chemistry, Faculty of Chemistry, University of Lodz, 

Pomorska 163/165, 90-236 Lodz, Poland.

We compare performance of several computational methods describing chemical

systems at various theory levels in search of the ground state of molecules. The quality of theoretical methods was examined for two azacrown ethers: 4,7,13-trioxa-1,10-diazacyclopentadecane (A) and its recently synthetized derivative [1], namely 1,10-N,N’-Bis-(β-D-ureidoglucopyranosyl)-4,7,13-trioxa-1,10-diazacyclopentadecane (B). This new pseudocryptand contains glucose substituents which are likely to interact with other molecules. As was shown in [1], indeed it forms complexes with selected drugs (eg. aspirin, paracetamol) and so can be used as a potential drug carrier.

Since for such molecules the configurational space is very vast, to find the lowest energy conformers we used several different techniques such as extended conformational search (available in the Hyperchem program [2]) using molecular mechanics, followed by semiempirical (PM6, PM7) and the DFT functional (B3LYP-GD2/6-31G(d,p)) optimizations. We used also the computer simulations method. The quantum mechanical calculations were performed both in vacuo and in aqueous solution (solvent described by the implicit model PCM) to account for the solvent effect. We show that each of the methods tested points toward a different conformer as the most stable geometry. The energy differences between several lowest energy structures are also analyzed.

Figure 1. Molecules studied: (A) 4,7,13-trioxa-1,10-diazacyclopentadecane, (B) 1,10-N,N’-Bis-(β-D-

ureidoglucopyranosyl)-4,7,13-trioxa-1,10-diazacyclopentadecane. References [1] M. Pintal, B. Kryczka, S. Porwański Carbohydr. Res. 2014, 386, 18-22. [2] HyperChem(TM) Professional 8.0.10, Hypercube, Inc., 1115 NW 4th Street, Gainesville,

Florida 32601, USA.

P-027 

The influence of DFT functional on simulation of electric field effect on selected model molecule

Paulina Kozłowska1, Justyna Dominikowska1, Marcin Palusiak1 1 Department of Theoretical and Structural Chemistry, Faculty of Chemistry, University of Lodz,

Pomorska 163/165, 90-236 Lodz ,Poland.

4-nitro-benzonitrile molecule is an aromatic system, having two electron withdrawing

groups. Due to the above properties it is an interesting object for studies on the influence of external electric field exalted on the model aromatic system. In order to calculate the aromaticity index the B3LYP functional was used. The choice of the functional was connected with the fact that it reflected a good performance in reproducing the structural properties of molecular systems, as revealed in the literature. [1] Making the systematic changes in the value of the external electric field in the range of -0.025 - 0.025au changes in the total energy of the system and the trace of dipole moment on the selected axis were screened

A good correlation occurred for values of total energy and the trace of dipole moment as estimated for various DFT functionals, which proves a lack of dependence of these parameters on the level of DFT calculations. For B3LYP functional a correlation between indexes aromaticity, however, the highest aromaticity of the system has been noticedat different field strengths, depending on the functional chosen.

Figure 1. Structure of 4-nitrobenzonitrile.

References [1] S. Rayne, K. Forest, Comput. Theor. Chem., 2011, 976, 105.

P-028 

1-(N-acetylamino)-1-(diethoxyphosphoryl)alkyltriphenyl-phosphonium salts a new method of synthesis and potential

synthetic applications Anna Kuźnik1, Magdalena Zięba1, Roman Mazurkiewicz1

1 Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, Poland.

anna.kuznik@polsl.pl

Recently we developed a few-stage transformation of N-acyl-α-amino acid derivatives

into symmetrical and unsymmetrical α-aminoalkylidenebisphosphoric acid derivatives 5 of medical importance.[1] However, as one of the key steps in this synthesis is electrochemical oxidation of the phosphonate analogue of a starting α-amino acid, a major limitation of this method is the inability to undergo electrochemical alkoxylation of phosphonates others than glycine and alanine analogues.

To overcome this problem, we propose a new method for synthesis of α-alkoxyphosphonates 3, where the starting compounds are imidate hydrochlorides 1 readily available from nitriles. These substrates may be effectively converted into α-ethoxyphosphonates 3 by the Michaelis-Becker-type reaction in mild conditions in a PTC system, after earlier acylation of their amino group. Subsequent displacement of the ethoxy group by the triphenylphosphonium group provides practically unknown, very interesting α-phosphonium derivatives 4 of α-aminophosphonates, that in fact are convenient materials in some further transformations due to increased electrophilicity of their α-carbon. Thus, we have demonstrated the possibility of carrying out the nucleophilic substitution of the triphenylphosphonium group with nucleophiles such as phosphorus or carbon, that lead to the above-mentioned bisphosphoric acid esters 5 and derivatives 6 respectively, as well as the β-elimination reaction resulting in α,β-dehydro-α-aminophosphonate 7, that is used for the asymmetric hydrogenation.[2]

  References [1] A. Kuźnik, R. Mazurkiewicz, M. Grymel, at al., Beilstein J. Org. Chem., 2015, 11, 1418–

1424. [2] A. Kuźnik, R. Mazurkiewicz, N. Kuźnik, Curr. Org. Synth., 2013, 10, 411-424.

P-029 

1-Imidocarbenium cations: generation and reactivity in the selected reactions of C-C bond formation

Jakub Adamek1, Anna Węgrzyk1, Roman Mazurkiewicz1 1 Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry,

Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, Poland

During the period of 2009-2013 we have developed the efficient methods for the synthesis of hardly known 1-(N-acylamino)alkylphosphonium salts 1 (Scheme 1).[1] It was also demonstrated that the abovementioned phosphonium salts, in a proper conditions, create amidoalkylating systems of high reactivity.[2] The important special feature of 1-(N-acylamino)-alkylphosphonium salts, that distinguish them from the other known amidoalkylating agents, is the permanent, positive charge of the leaving phosphonium group (Ph3P+), that eliminates the necessity of applying an acidic catalyst of amidoalkylation reaction.

Scheme 1.

In general, reactivity of N-acyliminium cation or N-acylimine precursors depends on: effectivity of the generation of N-acyliminium cation 2 or N-acylimine 3 from its precursor, the equilibrium constant of this reaction and reactivity of N-acyliminium cation/N-acylimine toward a nucleophile.

Recently we have demonstrated, that the problem of insufficient reactivity of N-acyliminium cations 2 toward some less active nucleophiles, e.g. inactivated aromatic compounds can be solved, in a significant extent, by replacing N-acyliminium cations 2 with more electrophilic 1-imidoalkylcarbenium cations 5. Higher electrophilicity of these cations is caused by electron withdrawing effect of two carbonyl groups at the nitrogen atom. As it was further shown, hitherto unknown 1-imidoalkylphosphonium salts 4, can serve as convenient precursors of 1-imidocarbenium cations 5.

Scheme 2.

As it was expected, 1-imidoalkylcarbenium cations 5 display much higher reactivity toward slightly activated or no activated aromatic hydrocarbons than their N-acylated analogues. Their high reactivity enables α-imidoalkylation of low active toluene and no activated benzene, what was not possible in the case of other amidoalkylating agents, including 1-(N-acylamino)alkyl-phosphonium salts. Acknowledgment The authors gratefully acknowledge financial support from the Lodz University of Technology DS./I-18/2015.

References [1] A. Nowak, A. Kowalska, J. Org. Chem., 2016, 83, 111-222. [2] Times New Roman, 12pt, Normal.

P-030 

Mechanistic aspects of the classical and non-classical course of the Tscherniac-Einhorn-type reaction Jakub Adamek1, Monika Krawczyk1, Anna Węgrzyk1

1 Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, Poland.

In 1901 Tscherniac described the reaction of N-hydroxymethylphthalimide with various

aromatic compounds.[1] A few years later, Einhorn extended this transformation to easily available N-hydroxymethylamides. This kind of electrophilic aromatic substitution thus has come to be known as Tscherniac-Einhorn reaction.[2]

The formation of a new CAr-C bond by the Tscherniac-Einhorn-type intramolecular amidoalkylation of aromatic compounds using modern amidoalkylating reagents and properly selected catalysts is one of the most interesting method for the formation of annulated carbo- and heterocyclic systems.[3] However, the T-E reaction and the intramolecular version of this reaction have some important limitations: usually they can be carried out only in the case of aromatic systems with increased electron

density, like alkoxy and polyalkoxyarenes, aminoarenes, indol, etc; the classical T-E reaction that leads to the expected amidoalkylation product 2 competes

with side reaction - after formation of the CAr-Cα bond, the splitting of the Cα-N bond with subsequent addition of the leaving group Z to Cα gives product 3 (Scheme 1).

Scheme 1.

The problem of the non-classical T-E reaction has never been a subject of wider

investigations, particularly, literature gives no information on factors deciding on classical or non-classical direction of the reaction. Total or partial elimination of the abovementioned limitations of the T-E reaction would significantly widen the scope of possible practical synthetic applications of the discussed reaction.

Our research allowed not only to understand the mechanism of abovementioned reactions but also develop optimal conditions for their classical or non-classical course. Acknowledgment The financial support of the National Science Centre, Poland (Grant No. 2015/19/D/ST5/00733) is gratefully acknowledged. References [1] H. E. Zaugg, A. M. Kotre, J. E. Fraser J. Org. Chem., 1969, 34, 11–13. [2] R. Mazurkiewcz, A. Październiok-Holewa, J. Adamek, K. Zielińska Adv. Heterocycl. Chem.

2014, 111, 43–94.

P-031 

Identification and quantification of polyphenols in chokeberry leaves extracts

Magdalena Efenberger-Szmechtyk1, Agnieszka Nowak1, Agata Czyżowska1 1 Institute of Fermentation Technology and Microbiology, Lodz University of Technology, Poland

magdalena.efenberger@gmail.com

The aim of this study was to analyze composition of polyphenolic extracts made from

chokeberry (Aronia melanocarpa) leaves. The effect of several solvents on extraction efficiency was also examined.

Chokeberry leaves were collected in August in the Lodz region. Polyphenols were extracted using 3 types of solvents: distilled water and aqueous solutions of ethanol (concentration of 30 and 60%). Total phenolic content was determined using Folin Ciocalteu method and antioxidant activity of extracts was examined using DPPH free radical scavenging method. Polyphenolic compounds were identified using LC-MS method and quantified using HPLC method.

The highest concentration of polyphenols and the strongest antioxidant activity was observed for 60% ethanol extract. Chokeberry leaves contained two major groups of polyphenols: phenolic acids (neochlorogenic, chlorogenic, cryptochlorogenic, p-coumaroylquinic and unknown hydroxycinnamic acid derivatives) and flavonoids (quercetin derivatives, kampferol rutinoside, and isorhamnetin rutinoside). Among phenolic acids - chlorogenic acid dominated, whereas among flavonols - quercetin derivatives were prevalent. Water extract revealed the highest concentration of phenolic acids, whereas the content of flavonols was the highest in 60% ethanol extract. In conclusion, the type of solvent influences extraction efficiency of polyphenols from chokeberry leaves and the composition of polyphenolic extracts.

P-032 

Experimantal and theoretical investigations of reactions between 1,1,1-trifluorodiazoethane and cycloaliphatic, aromatic

and heteroaromatic thioketones Marcin K. Kowalski1, Emilia Obijalska1, Radomir Jasiński2, Grzegorz Mlostoń1

1 University of Łódź, Faculty of Chemistry, Department of Organic and Applied Chemistry, Tamka 12, PL-91-403, Łódź, Poland.

2 Cracow University of Technology, Institute of Organic Chemistry and Technology, Warszawska 24, PL-31-155, Cracow, Poland.

In recent years fluorinated diazoalkanes such as trifluorodiazoethane (1) have widely been used as a very reactive 1,3-dipoles in diverse [3+2]-cycloaddition reactions which led to extremely important fluorinated heterocyclic products [1]. However, they have never been applied for the reactions with thiocarbonyl compounds (C=S dipolarophiles). Our ongoing studies showed that, the obtained results depends on the substituent present in the structure of used thiocarbonyl substrate 2. First experiments in this area showed that title diazo compound 1 easily reacts with sterically hindered tetramethylcyclobutane-derived thioketones yielding regioselectively 1,2,4-thiadiazolines of type 3. In the case of aromatic thioketones appropriate thiiranes 4 or desulfuration products (alkenes 5) were obtained, respectively. When heteroaromatic thioketones were used, more sterically hindered dithiolane were observed as a final product [2].

In the case of obtained stable thiadiazolines 3, their thermal decomposition in the presence of diverse dipolarophiles were performed; only aromatic and heteroaromatic thioketones gave desired products.

It should be underlined, that is very probably, that in reactions leading to fluoroalkylated adducts, stepwise cycloaddition mechanism compete with “classical” concerted one. In order to explain the question comprehensive theoretical studies were initiated. In particular, analysis of intermolecular interaction between addent on the basis of conceptual Density Functional Theory was performed. Additionally, theoretically possible reaction paths for model processed was explored. Premilimary results of these theoretical study will be presented.

Scheme 1. Presentation of title substrates and products obtained during the studies.

Acknowledgment Financial support by the National Science Center (Poland-Cracow) Grant PRELUDIUM-8 (UMO-2014/15/N/ST5/02895) is gratefully acknowledged. This research was supported in part by PL-Grid Infrastructure. References [1]. (a) Pavel K. Mykhailiuk Org. Biomol. Chem. 2015, 13, 3438; (b) Pavel K. Mykhailiuk

Beilstein J. Org. Chem. 2015, 11, 16; c) F.-G. Zhang, Y. Wei, Y.-P. Yi, J. Nie, J.-A. Ma, Org. Lett. 2014, DOI: 10.1021/ol501249h.

[2]. M. K. Kowalski, E. Obijalska, R. Jasiński, G. Mlostoń, in preparation.

P-033 

New Eco-friendly Method for the Synthesis of Chiral Hydroxyphenylselenides

Julianna Mruk1, Agata J. Pacuła1, Claudio Santi2, Jacek Ścianowski1* 1 Department of Organic Chemistry, Faculty of Chemistry, Nicolaus Copernicus University in Torun,

7 Gagarin Street, Torun, Poland. 2 Department of Pharmaceutical Sciences, Group of Catalysis and Organic Green Chemistry,

University of Perugia, Via del Liceo 1-06100 Perugia Italy. * jsch@chem.umk.pl

Synthesis of organoselenium compounds is one of the most important areas of modern organic chemistry. These compounds exhibit interesting biological and pharmacological properties. The introduction organoselenium groups and their further transformations are possible with very good chemo-, regio- and stereoselectivity. The presence of carbon-selenium bond allows a homolytic cleavage, syn-elimination or nucleophilic substitution that affords allylic alcohols, diols, epoxides, amides and dihydroxy diselenides. [1-4]

Here we present a new eco-friendly methodology for the synthesis of chiral hydroxyphenylselenides derived from terpenes, based on the reaction of epoxides and di(phenylselenyl)zinc. Selenium reagent PhSeZnSePh was prepared by the reaction of diphenyl diselenide and zinc dust, under ultrasound irradiation in the presence of THF and a catalytic amount of 10% HCl (Scheme 1). Epoxide ring opening in water at 90oC leads to the formation of optically active β-hydroxyphenylselenides from carane group and additionally trans-hydroxyphenylselenides with cyclopentane, cyclohexane and propane moieties. The control of the reaction condition by the addition of NaHCO3 or HCl determines the stereochemistry of the obtained products. Developed new methodology based on the use of water as the solvent from renewable natural sources respects the principle of Green Chemistry.

Scheme 1. Synthesis of di(phenylselenyl)zinc.

The structures of all drivatives were confirmed by IR, 1H, 13C, 77Se NMR analysis.

References [1] A. J. Pacuła, F. Mangiavacchi, L. Sancineto, E. J. Lenardao, J. Ścianowski, C. Santi,

Curr. Chem. Biol., 2015, 9, 97–112 [2] J. Ścianowski, Z. Rafiński,. Electrophilic selenium reagents: Addition reactions to double

bonds and selenocyclizations. In: Organoselenium Chemistry: Between Synthesis and Biochemistry; Santi, C., Ed.; Bentham, 2014; pp. 8-60.

[3] J. Drabowicz, J. Lewkowski, J. Ścianowski. Selenium Compounds with Valency Higher than Two In Organoselenium Chemistry, Wirth T. (ed.) Wiley-VCH: Weincheim, 2012, 119-256.

[4] A. J. Pacuła, J. Ścianowski, Current Green Chemistry, 2016, 3, 36-50.

P-034 

N-Aryl Ebselen-like Antioxidants Magdalena Obieziurska1, Agata J. Pacuła1, Jacek Ścianowski1*

1 Department of Organic Chemistry, Faculty of Chemistry, Nicolaus Copernicus University in Torun, 7 Gagarin Street, Torun, Poland.

* jsch@chem.umk.pl

Excessive ROS production, overcoming the antioxidant defence system of the living cell, is called „oxidative stress“. Ebselen (2-phenyl-1,2-benzisoselenazole-3(2H)-one) was the first example of a synthetic GPx mimic with the ability to remove ROS [1]. The other selenoorganic compounds suc