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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
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Printed by PROXIMA Sp.z o.o., Krańcowa 55, 94-305 Łódź,
2016.
ISBN 978-83-7455-520-3
http://www.cbmm.lodz.pl/
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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
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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
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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
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PLENARY LECTURES
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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.
[email protected]; [email protected]
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
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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
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PL-2
Philicities, Fugalities, and Equilibrium Constants Herbert
Mayr1
1 LMU München, Department Chemie, Butenandtstr. 5-13, 81377
München, Germany [email protected]
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.
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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.
[email protected]
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.
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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.
[email protected]
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.
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INVITED LECTURES
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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. [email protected]
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.
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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. [email protected]
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.
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POSTERS
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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.
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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.
[email protected]
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.
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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.
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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.
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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. [email protected],
[email protected]
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.
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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.
[email protected]
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.
[email protected]
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.
[email protected]
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.
[email protected]
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. [email protected] 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. [email protected]
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.
[email protected], [email protected]
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. [email protected],
[email protected]
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.
[email protected]
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. [email protected]
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.
[email protected]
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.
[email protected]
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.
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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.
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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
[email protected]
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.
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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.
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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. *
[email protected]
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.
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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.
* [email protected]
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