Area of Organic Chemistry - Dept. of Industrial Chemistry University of Bologna - Università di Bologna
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Area of Organic Chemistry Dept. of Industrial Chemistry University of Bologna
Area of Organic Chemistry - members
Permanent positions (11):
Prof. Andrea Mazzanti full professor
Prof. Giorgio Bencivenni associate professor
Prof. Luca Bernardi associate professor
Prof. Mauro Comes Franchini associate professor
Prof. Mariafrancesca Fochi associate professor
Prof. Daniele Nanni associate professor
Prof. Paolo Righi associate professor
Prof. Letizia Sambri associate professor
Prof. Carla Boga associate professor
Prof. Emanuela Marotta assistant professor
Prof. Paolo Zani assistant professor
RTD-B (senior researcher): Dr. Michele Mancinelli
PhDs: 3-4 post-docs: 3-4 post-grad grants: 1-2
Master Thesis internships: 8-10
Main area and department research facilities • NMR spectrometers (300 MHz, 400 MHz, 600 MHz) • Analytical HPLC on chiral stationary phase • Preparative HPLC also on chiral stationary phase • VCD-ECD • MS spectrometers (GC-MS, ESI); • Single-crystal X-Ray diffractometer (access to powder XRD);
Topics & Laboratories - Development of nanostructured systems based on metallic nanoparticles (CHINANOR-Nanni) - Composite materials for energy storage and sensing applications (CHINANOR-Nanni) - Metal organic frameworks (MOFs) - suitable porous materials for catalytic application (CHINANOR-Nanni) - History of chemistry through XVIII and XIX centuries – chemistry as «scientia nova» (Zani) - Development of new catalytic enantioselective reactions (OCSA-Bernardi- Fochi) - «Blue chemistry»: marine biopolymer gels in catalysis (OCSA-Bernardi-Fochi) - New organocatalytic enantioselective vinylogous reactions (OCSA- Bencivenni-Marotta-Righi) - Organocatalytic enantioselective formation of atropisomers (OCSA- Bencivenni-Marotta-Righi)
Topics & Laboratories - Synthesis of compounds as anticancer agents and related studies on their drug delivery (Boga) - Synthesis of highly conjugated organic compounds for applications in optoelectronic field (Boga) - Detection of labile intermediates of aromatic substitution reactions (Boga) - DFT Calculations (OCSA-Mancinelli-Mazzanti) - Structural analysis (OCSA-Mancinelli-Mazzanti) - Additive Manufacturing (3D-Printing) (ASOM-Comes-Sambri) - Bio-Ink for biomedical applications (ASOM-Comes-Sambri) - Theranostic: Therapeutic + Diagnostic (ASOM-Comes-Sambri) - Sensing for organic electronics (ASOM-Comes-Sambri)
Department of Industrial Chemistry «Toso Montanari», Viale Risorgimento 4, BO, IT-40136
web site: https://chimica-industriale.unibo.it/it/ricerca/gruppi-di-ricerca/chinanor
Prof. Daniele Nanni, Organic chemistry «only a 360 degrees knowledge of materials
daniele.nanni@unibo.it
https://www.unibo.it/sitoweb/daniele.nanni allows to take full advantages from their
properties»
Prof. Barbara Ballarin, Analytical Chemistry
barbara.ballarin@unibo.it
https://www.unibo.it/sitoweb/barbara.ballarin
CHINANOR Nanomaterials is a multidisciplinary
team made by three researchers with consolidate
Prof. Maria Cristina Cassani, Inorganic Chemistry
maria.cassani@unibo.it skills in CHemistry, in particular in the field of
https://www.unibo.it/sitoweb/maria.cassani INorganic, ANalytical and ORganic chemistry.
Dr. Francesca Gambassi, PhD student Topics:
francesca.gambassi2@unibo.it
planning, synthesis and characterization of new
nanostructured materials for catalytic,
Dr. Ilaria Ragazzini, PhD student
Ilaria.ragazzini6@unibo.it environmental and energetic applications.
THE NANOWORLD FOR INDUSTRIAL APPLICATIONS
Development of nanostructured systems based on metallic nanoparticles
This aspect of research develops synthetic/electrosynthetic Au
Au
Au
procedures to obtain nanostructured systems based on metallic Au Fe3O4 Au
nanoparticles (Au, Ag, Pt etc.) supported on different substrates Au
Au
Au
(silica, allumina, titania, magnetite, hydrotalcite, cellulose, etc.)
funzionalized with organic residues.
The obtained systems, completely characterized from the chemical-
phisical point of view, are used as:
a) catalysts for some organic syntheses;
b) applications in the environmental and cosmetic field.
HAuCl4
Au Au Au
Au
Au/SiO2@Yne
COMPOSITE MATERIALS FOR ENERGY STORAGE AND SENSING APPLICATIONS
The goal of this kind of research is to find more environmental
friendly sistems for future industrial applications. The research can
be devided into two main topics:
1. Energy storage applications: electrodepositation of thin films
based on conductive polymers modified with different kind of
nanoparticles like inorganic oxides, and the study of their
properties with the aim of making devices able to store energy; PMMA
2. Paper electronics: modification of bare fibers of cellulose with
conductive polymers to create materials with high conductivity
and flexibility to make smart and cheap sensors with different
applications (touch sensors and gas sensors for example).
Bare
cellulosic
fibers
Modified
fibers
METAL ORGANIC FRAMEWORKS (MOFs) - SUITABLE POROUS MATERIALS
FOR CATALYTIC APPLICATION
Development of MOFs systems containing gold nanoparticles. Metallic kink
For create a
The Aim of this project in three key steps: specific geometry
And for possible
bifunctional
• Synthesis of new organic linker able to react with catalysis
copper ions leading to the construction of a new,
porous crystalline material
Organic linker
Cu-MOF. for the
construction of
• Characterization of the new material by means of Cu-MOF and the
support of Au-
several complementary techniques such as NMR NPs
spectroscopy, IR-ATR spectroscopy, atomic absorption
spectroscopy (AAS), thermogravimetric analysis
(TGA), Raman analysis.
Hosted species
With special catalytic
• Realization of a useful platform with high surface properties for various
area capable of hosting gold nanoparticles due to his organic reaction
porosity and his organic funcionality, with promising Cu-MOF
catalytic capacities.
Collaborations • Prof. Carla Boga, Dipartimento di Chimica Industriale «Toso Montanari»: Preparation of new magnetic nanoparticles coated with (R)-9-Acetoxystearic Acid for Biomedical Applications. • Università Politecnica delle Marche: preparation of inorganic/organic scintillators. • Dipartimento di Chimica "Giacomo Ciamician", Università di Bologna: XRD, TGA, TEM. • Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Ferrara: Flow Chemistry. • Dipartimento di Scienze Chimiche, Università di Padova: XPS, FE-SEM. • Consiglio Nazionale delle Ricerche di Bologna e Faenza.
History of sciences (Zani) Development of chemistry through XVIII and XIX centuries: Chemistry as «scientia nova», a methodological and documental approach. For information: paolo.zani@unibo.it
Research topics – OCSA (Bernardi-Fochi)
1) Development of new catalytic enantioselective reactions:
Using known organic catalysts (different classes), we explore new chemistry
and reactivity.
Phase-Transfer Catalysis Aminocatalysis Synergistic Catalysis H-Bond and bifunctional catalysts
O
Ar Ar R
H - Ar Ar N
X O
HO N N OTMS O O + [Pd] H H
H P O O N
R R O O H P H N
O O H R
O N Ar
N
Ar
Ph N N
H
-Dearomatization of activated pyridines: A student involved in such a project will learn how to:
Nu H -perform multi-step organic synthesis (catalysts and
Ewg Ewg
piperidines
substrates)
N N -characterise organic compounds (NMR, HPLC analysis)
R R -perform extensive optimisation of reaction
-aza-Diels-Alder cycloadditions: coinditions.
R2
R2
R3
For additional information:
N
+
R3
N R1
luca.bernardi2@unibo.it
R1 H
mariafrancesca.fochi@unibo.itResearch topics – OCSA (Bernardi-Fochi)
2) «Blue chemistry»: marine biopolymer gels in catalysis:
Aginate biopolymers (algae extracts) readily form gels (solvogels, aerogels)
with high surface areas and functional group density: applications in
catalysis and adsorption.
Aerogel:
1) Purification Same properties of a
gel (surface are 600
2) Acidification and gelification
m2g-1)
3) From hydrogel to solvogel to aerogel All functionalities are
accessible
N
N S N
A student involved in such a project will learn how to:
Cl -perform simple organic synthesis
-prepare and manipulate hydro and solvogels
-characterise organic compounds (NMR, HPLC analysis)
Adsorption -perform extensive optimisation of reaction coinditions
For information:
luca.bernardi2@unibo.it
Currently pursued: is it possible to exploit the intrinsic mariafrancesca.fochi@unibo.it
homochirality for enantioselective processes?Research topics – ORG (Bencivenni*-Marotta-Righi)
1 - New organocatalytic enantioselective 1 PhD student
vinylogous reactions: 1-3 Master (6-9 months) students
γ'-site pathway
dienolate forms
γ-site pathway
2-3 Bachelor (3-6 months) students
γ' BH
1 post-doc
H γ
1 industrial granted position
H
- -
O O O
N N N
-BH H H
H
s-trans s-cis 2 – Organocatalytic enantioselective
formation of atropisomers:
3-Collaboration with fine chemical SMEs:
FATRO S.p.A. - Veterinary
Pharmaceutical Industry
40064 Ozzano dell’Emilia (BO) Italy
Endura S.p.A. - PBO and synthetic
pyrethroids
Headquarters in Bologna,
manufacturing and R&D in RavennaResearch topics – (Bencivenni-Marotta-Righi)
1) New organocatalytic enantioselective vinylogous reactions:
• Vinylogous reactivity is a valuable strategy for the remote modification of a molecule.
• Vinylogous addition of alkylidene oxindole on aryl trifluoromethyl ketone resulted in a rare
aldol reaction-lactonization cascade. The reaction, catalyzed by a bifunctional tertiary amine,
provides an efficient entry to enantioenriched trifluoromethylated α,β-unsaturated δ-lactones.
• The addition on α,β-unsaturated trifluoromethyl ketones provided an efficient preparation of
enantioenriched trifluoromethylated allylic alcohols
O O
Ar CF3 Ar CF3
R'
cat (10 mol%) cat (10 mol%)
PhCF3, rt, 72 h O THF, rt, 24 h
N
Boc
Aldol Lact Aldol
Boc O CF3 Ar
HO
NH H N
O R'
O NH
N Ar
CF3 S N O Bencivenni, et al. J. Org. Chem. 2018, 83, 12440.
R Ar H N Bencivenni, et al. RSC Adv., 2018, 8, 33451
I-9-epi-HQAT Boc
up to 99% yield Ar = 3,5-(CF3)2-C6H3
up to >99% ee up to 88% yield
up to 95% eeResearch topics – (Bencivenni-Marotta-Righi)
2) Organocatalytic enantioselective formation of atropisomers:
• Enantioselective organocatalysis has been successfully applied to the synthesis of atropisomers
• Desymmetrization of N-arylmaleimmides by nucleophilic attack on their prochiral double bond
afforded atropisomeric succinimides
O
H N
NH
H
N N
O
O
R2 R3 R2 O atropisomeric C-N axes
F 3C CF3
N
catalyst J (10 mol%) R3 trisubstituted carbon stereocenter
+
R1 O O N O H O
CH2Cl2 [0.25M] R1 O
N
25 °C, overnight
Boc
N
Boc
tetrasubstituted carbon stereocenter Bencivenni, et al. Synthesis, 2017, 49, 1513.
• Axially chiral cyclohexylidene oxindoles were selectively obtained by means of organocatalytic
Knoevenagel condensation. Insights on the mechanism were obtained by DFT methods
R
R R1 Ph
O
O + Ph
Im R2
R1 N HN H
H H
R2 O
R
OH H N
∗
H
O Ph
H N O
H H
∗
Axially chiral cyclohexylidene O
O Bencivenni, et al. Org. Lett., 2019, 21, 3013.
Enantioselective axially chiral R
Knoevenagel condesationResearch topics – (Boga)
Synthesis of compounds as anticancer agents and
related studies on their drug delivery
Recent studies have been devoted also on the
Synthesis of (R)-9-hydroxystearic acid [(R)-9-HSA] and its derivatives
synthesis of novel compounds as substitutes of
(R)-9-HSA can be obtained in high yield from Dimorphotheca sinuata
APCIN in the treatment of acute myeloid leukemia.
seed oil through a simple multistep procedure.
RECENT PUBLICATIONS
O
HO H Boga, C. et al.: Redox signaling via lipid peroxidation
regulates retinal progenitor cell differentiation.
OH Developmental Cell 2019, 50, 1-17.
8 7
Boga, C. et al.: X-Ray Crystal Structures and Organogelator
(R)-9-hydroxystearic acid Properties of (R)-9-Hydroxystearic Acid. Molecules 2019, 24
Dimorphotheca sinuata (15), 2854.
(R)-9-HSA is an endogenous cellular lipid that, when administered to
Boga, C. et al.: Unprecedented behavior of (9R)-9-
different human cancer cell lines (colon, bone, leukemia cells, etc.) hydroxystearic acid loaded keratin nanoparticles on cancer
produces tumor cell growth arrest without effect on normal cell lines. cell cycle. Mol. Pharmaceutics 2019, 16, 931-942.
It acts as an inhibitor of enzymes belonging to the hystone
Boga, C. et al.: Synthesis of 9-Hydroxystearic Acid Derivatives
deacetylase classes. Recently the interest has been focused on its and Their Antiproliferative Activity on HT 29 Cancer Cells.
drug-delivery: it has been succesfully inserted in hydroxyapatite Molecules 2019, 24, 3714.
nanoparticles (Langmuir 2016), Keratine nanoparticles (Mol Pharm
2019) and, more recently, in magnetite nanoparticles (ACS Omega, Collaborations
in press). (R)-9-HSA behaves as organogelator, an interesting Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
property in material field (Molecules, 2019). Also the synthesis of Meldola (FC)
Dipartimento FABIT – University of Bologna.
structural hybrids bearing the HSA scaffold is work in progress. Dipartim. Di Chimica e Scienze Farmaceutiche. Univ. TriesteResearch topics – (Boga)
Synthesis of highly conjugated organic compounds for
applications in optoelectronic field
Synthesis and properties of solid state fluorescent Novel highly conjugated architectures from C–C
materials coupling between aminothiazoles, diamino- or sym-
Y
triamino-benzenes and benzofurazan- or
X Z
benzofuroxan- derivatives.
-
N2 BF4
+
H3CO OCH3
CH3CN Boga, C. et al.: New azo-decorated N-pyrrolidinylthiazoles:
+ N
RT N synthesis, properties and an unexpected remote substituent effect
HBF4
OCH3 X Z O O transmission Org. Biomol Chem 2016,14,7061-7068.
Y
Boga, C. et al.: Coupling Reactions between Benzofurazan
O
Derivatives and 1,3-Diaminobenzenes. Molecules 2017, 22, 684.
Boga, C. et al.: Highly conjugated architectures and labile reaction
intermediates from coupling between 10π electron-deficient
heteroaromatics and sym-trihydroxy- or triaminobenzene
derivatives.” RSC Adv., 2018, 8, 41663-41674.
Recent and current topic:
Synthesis of organic compounds for applications as scintillators
Collaborations
Istituto per la sintesi organica e la fotoreattività (ISOF-CNR Bologna)
Proff. Nanni, Cassani, Ballarin (CHIMIND)
Dipartimento di Fisica e Ingegneria dei Materiali e del Territorio, Università Politecnica delle Marche.Research topics – (Boga)
Detection of labile intermediates of aromatic
substitution reactions
The C-C coupling between strongly activated aromatic neutral nucleophiles (Nu) and electrophiles (E) allowed the
first detection and characterization of Wheland-Meisenhemer (WM) intermediates, contemporarily of the SEAr
(Wheland) and of the SNAr (Meisenheimer) (Boga, C. et al.: Angew.Chem. 2005, 44, 3285-3289).
This paved the way to many other examples, with different Nu/E combinations and the topic is yet in progress.
NR2 Wheland (W) have also been detected
Neutral carbon Neutral carbon
H E
supernucleophile superelectrophile R2N
G G G G
NR + + – +
O HO 2 E X X–
H
R2N NR2 O 2N N O2N N
- G
+ O O G
N N G = electrondonor group
W
NR2 NO2 DNBF NO2 E+X– = benzenediazonium salt
+
E BF4– = benzhydrilium tetrafluoroborate (in
NR2 = N-piperidinyl, N-morpholinyl, N-pyrrolidinyl Zwitterionic Wheland-Meisenheimer
collaboration with Prof.Herbert Mayr
intermediate (WM)
Department Chemie -Ludwig-Maximilians-Universität München
Other WM from the following combinations
Nu = sym-triaminobenzenes, E = 4,6-dinitrotetrazolepyridine (DNTP) (JOC 2009)
Nu = sym-triaminobenzenes, E = 2,3,4-trinitrothiofene (Org. Biomol. Chem. 2016)
Nu = 2-aminothiazole E = DNBF (Chem. Eur. J. 2007)
Nu = 2,4-dipyrrolidinylthiazole E = DNBF e DNTP (Eur. J. Org. Chem. 2012)Research topics – (Mazzanti - Mancinelli)
Synergistic Catalysis: Highly Enantioselective
Acetyl Aza-arene Addition to Enals
Chem. Eur. J. 2018, 24, 13306-13310Research topics – (Mazzanti - Mancinelli)
DFT Calculations
The zinc enolate can approach the iminium
ion in an ’’endo’’ geometry driven by a more
favorable interaction between the HOMO of
the enolate and the LUMO of the iminium
ion, with the zinc and the nitrogen of the
iminium ion involved in the HOMO-LUMO
interaction. This geometry is more stable
than the ’’exo’’ by more than 3 kcal/mol, and
it accounts for the formation of the S
enantiomer when R-catalyst is used (Fig 1)
The TS involving the second addition is
similar to that of the first step with the E
geometry of the iminium ion. Again the endo
geometry with zinc over the nitrogen is
favored with respect to the exo, and the most
stable TS involves the attack the Re face of
the zinc enolate. This TS forges the second
stereocenter with S-configuration. (Fig 2)Research topics – (Mazzanti - Mancinelli)
Research topics – (Mazzanti - Mancinelli)
Structural analysis
2D-COSY experiments
Relative configuration
NOE-NMR
experiments
Conformational analysis
with MM
Conformation
DFT optimization
Experimental ECD
Absolute configuration
TD-DFT calculation of
ECD spectrumResearch topics – (Mazzanti - Mancinelli)
Example for Compound 3i-minor
NC
15
Experimental ECD spectrum
NC NC
14 12 6
19 13 1 5 35
20 18
1 1
21 17
2 4 30
N 16
3 7 H-3 2 2
8 O 25 N
3
N
3
O 9 O O
20 O O
H-9 -
3i minor 10 -
3i major
-
3i minor
11 15
CN
10 CN CN
H-1
H-13 5 CD3CN at +25 °C
mdeg 0
190 210 230 250 270 290 310 330 350 370 390
NOE-NMR -5 nm
{H-2}
-10 3i-major
600 MHz in CDCl3
3i-minor
at +25 °C -15
-20
TD-DFT ECD spectra
H-7
H-5
H-9 H-13
3i-minor
1S,2S,3S
H-2 H-3
mdeg
H-1
H-6b H-6a nm
6-311++G(2d,p)
1H-NMR
600 MHz in CDCl3 Relative configuration Absolute configuration
at +25 °C 3i-minor 1S*,2S*,3S* 3i-minor 1S,2S,3SResearch topics – (Mazzanti - Mancinelli)
Chemodivergent Preparation of Multiple Heterocycles via Phase-Transfer
Catalysis: Enantioselective Synthesis of Functionalized Piperidines
-Exploiting the pluripotency of substrates 1 with PTC:
chemo-divergent synthesis of heterocycles
CO2R2
CO2Me R1
ArS
OH OH
ArS
Me N
Pathway a
Ts
ArSH 2 X piperidines enantioenriched
3 thianes
piperidines
Tethering THpyranes
heteroatom
CO2Me
O CN
MeO2C X Pathway b O
1 Me Me
"-CN"
Electrophilic X morpholines
sites
4 1,4-oxathianes
1,4-dioxanes
MeO2C NC CN
Pathway c OH -Nucleophile directs the pathway
NC CN Me
-DFT calculations explain
X the chemo-divergency (a) vs (b)
5
-Asymmetric catalysis:
piperidines enantioentiched piperidines
THpyranesResearch topics – (Mazzanti - Mancinelli)
Pathway A
O OMe
TMA
PhS
O
N
O OMe Ms O OMe
TMA
H 2O PhS (S*) O TSC 1a* TSA PhS (R*) O TMA H 2O
3''aa* 3aa*
not observed -TMAOH (R*) (R*) Me (R*) (R*) Me -TMAOH observed, major
N N
Ms Ms
IntC Activated IntA
complex
O OMe O OMe
TMA
PhS (R*) O PhS (S*) O TMA
H 2O TSD TSB H 2O
3'''aa* (S*) (R*) Me (S*) (R*) Me 3'aa*
not observed -TMAOH -TMAOH observed, minor
N N
Ms Ms
IntD IntBResearch topics – (Mazzanti - Mancinelli)
Pathway B MeO O CN
A Me H 2O 4a*
MeO TS2(R*,S*) (R*) (S*)
TMA TMA O
TMA O -TMAOH observed
CN CN TMA N
O O TS1A CN Ms
Ms Activated O
N Me Int2(R*,S*)A
complex A
MeO Me TS2(R*,R*)A H 2O
MeO O CN 4'a*
1a* N
Ms (R*) (R*) Me -TMAOH not observed
Int1A O
TMA N
Activated Ms
complex B Int2(R*,R*)A
O OMe O OMe O OMe
TMA
NC O TMA NC OH
NC
TS1B TS2B Me H 2O Me
O -TMAOH
N N N
Ms Ms Ms
Int1B Int2B 4''a*
not observed
16.3 17.0
TS2(R*,S*)A
TS1B
10.8 TS2(R*,S*)A
TS1A 14.0 8.6
Int2(R*,S*)A
+TMAOH
-H2O
1.4 Int2(R*,S*)A
TS2B 4.5
Int1A -2.0
3.2 4’a*
Activated complexes
A (0.0) and B (0.4)
4a*
-3.0
Int1B +TMAOH
-6.5 -H2O
Int2B
-14.8Advanced Smart Organic Materials (ASOM)
WEB: https://chimica-industriale.unibo.it/it/ricerca/gruppi-di-ricerca/advanced-smart-organic-materials-asom
Contact: Prof. Mauro Comes Franchini mauro.comesfranchini@unibo.it Prof. Letizia Sambri letizia.sambri@unibo.it
The research group activity is focused on the optimization of innovative processing techniques with the aim of developing
new organic materials for applications in the field of nanomedicine and organic electronics, for industrial applications.
Processing techniques include:
• Additive Manufacturing (3D-Printing) in order to obtain new materials starting from natural pool sources, such as
carbohydrates and proteins. The starting biomaterials are synthetically modified before being applied to the
manufacturing.
• Bio-Ink for biomedical applications via gel-extrusion deposition. Here too, biocompatible materials are investigated:
the formulations are thoroughly explored and optimized in order to obtain suitable rheology for building scaffolds
eligible for Tissue Engineering.
The group has proven expertise in synthesis of luminescent molecules and organic functionalization of metal-conductive
and piezoelectric nanostructures (gold, silver, metal oxides) with different size and shapes. Integration of these features
with the above-mentioned Processing Techniques give main applications as:
Theranostic (Therapeutic + Diagnostic) in biomedical field. European project undergoing https://chimica-
industriale.unibo.it/it/ricerca/progetti-di-ricerca/novel-precision-technological-platforms-to-promote-non-invasive-early-
diagnosis-eradication-and-prevention-of-cancer-relapse-proof-of-concept-in-the-bladder-carcinoma
Sensing for Organic Electronics.
Available Positions: One from october 2020 and Two starting march 2021You can also read
