synthesis and applications of functionalized (thia)calixarenes
TRANSCRIPT
A.E.Arbuzov Institute of Organic & Physical Chemistry, KazanA.M.Butlerov Chemistry Institute of Kazan State University, Kazan
Synthesis and applications of functionalized (thia)calixarenes
Moscow, 26-30 October 2009
I.S.Antipin, I.I.Stoikov, S.E.Solovieva, A.I.Konovalov
Macrocyclic platforms
O
OH
OO
OH
OH
OH OH
O
OH
OOH
OHOH
R
O HX n
HOOH HO
OHOH
HOOHHO
R RR
R
Calixarenes
CalyxCalyx CPKCPK--ModelModel
XXX XH H H H
SSS S
XXX XH H H H
X=O, S, NH
OOO OH H H H
Calix[4]arenes
SSS S
OOO OH H H H
The characteristic advantages of calix[4]arenes for the constructing of receptors are followed:
the low cost and accessibility of parent macrocycles by one-pot synthesis;
calixarenes can incorporate the small hydrophobic organic molecules into their molecular cavities with the formation of the stable host-guest complexes;
the existence of variety of calixarene conformations: cone, partial cone, 1,2-alternate, 1,3-alternate etc.;
calix[4]arene conformations are rather rigid and are able to fix the required spatial orientation of binding centers;
nontoxicity of calixarene platforms.calixarene platform gives an unique possibility to decorate the upper
and lower rim of macrocycle by the suitable heteroatom groups and to form the molecular system possessing the several binding centers;
1997 – S.Miyano et al
Thiacalix[4]arene
O OOO
H HH H
OH
HO
HO
OH
OOH H
HO
HO
OO
H H
HO
H
O
Cone Partial Cone
V≈10A3
1,3-Alternate 1,2-Alternate
Background of Calixarene Chemistry
Main Problem:
Stereo and Regio Selective Functionalization of Lower and Upper Rim
SSS S
OHOHOH OH
Upper Rim
Lower Rim
Mono, Di, Tri and Tetra Substituted Derivatives
O OOO
R RR R
OR
RO
RO
OR
OOR R
RO
RO
Cone Partial Cone 1,3-Alternate 1,2-Alternate
OO
R R
RO
R
O
1.Design of new types of cavitands2.Design of hosts molecules3.Design of tectons for MOFs
Main topics
O OOOH H
X
OO O OHH
X
OO O OHHH H
Br-X-BrK2CO3
O
2 X=
3 X=
1 X=
OO
OO
HH
O
O
O
O
OO
HH
O OOO
O OOO
HH
HH
OO O OHH
OO
OO H
H OO
OOH
H
O OOO
OO O OHH
HH
3 (45%) 4(23%)2 (33%)1 (30%)
Design of new types of cavitands
X
O N-H
RO
XS
X XXSS S
XRRX
RX+
O NHR
SXX XX
SS S
O NH HN OHN OR R R
-
Lower rim complexes: recognition of the charged species and surfaces
SS
SS
-O3S
-O3S SO3-
SO3-
OOHO
n+M
-O
A.I.Konovalov, I.S.Antipin Mendeleev Commun., 2008, 18, 229-237.
Low selectivity
High selectivity
SOH
4 4
SO
(CH2)nY
Hal(CH2)nY
M2CO3, CH3CN
Stereoselective synthesis using template effect
Y = group capable to bind cations:–C(O)NEt2, -C(O)-Ph , n = 1
S SO
RO
OSS
RO
RR
SOO O O
S SS
H H HH
M2CO3, RY
SOO O O
S SS
R R RR
SO
OO
SS
OS
RR
R
R
+ +
R Base
Reagentsratio
TCA:XR : M2CO3
Products distribution, %
Cone Partial cone 1,3-Alternate K+- 1,3-Alternate
Na2CO3 1 : 8 : 4 - - -
K2CO3 1 : 8 : 4 - 58 10 24K2CO3 1 : 8 : 6 - 11 -
79Сs2CO3 1 : 8 : 4 - 11 62
-
CH2C(O)Ph
Na2CO3 1 : 6 : 6 86 7 -
K2CO3 1 : 6 : 6 - 75 -
Сs2CO3 1 : 6 : 6 7 40
88
CH2C(O)NEt2
OO
R R
R
O
R
O
1,2-AlternateNot found
Stereoselective synthesis using template effect
O H O H
SS SS
O H O H
1
OS S
O
O
S
OPCl
PCl
2 δ(31P): 170.2 ppmm/z = 848[M+H+]
2 PCl3 ( N Et3) S
OS S
O
O
S
OP
Et2N
PN Et2
S
OS S
O
O
S
OPCl
O
PClO
S
4 δ (31P): 134.3, 140.4 ppmm/z = 924[M+H+]
3 δ (31P): -4.2 ppmm/z = 880[M+H+]
[O2]
HNEt22h, 90oC
Organophosphorus Derivatives of Thiacalix[4]arenes
SOO O O
S SS
H HHH
OP
OCl
PO
S
O
O
S
O SS
P
O
OO O OH HHH O
PO O
OO
H
POH
OP
OCl
OHO
PO
Cl OP
O
H
OCl
Кормачев В. В. Препаративная химияфосфора. / В. В. Кормачев, М. С.
Федосеев.- Пермь: УрО РАН, 1992. - C. 457.
(95%)
(56%)
Organophosphorus Derivatives of Thiacalix[4]arenes
Stabilization of monosubstituted derivative
1 2
H
SS
S S
O
O
O
O
HH
H
NH
NO2
H
SS
S SO
O
O
OHO
H
Base Solvent Time, h Yield, % 1 2 3 4 5
Na2CO3 CH3C(O)CH3 72 37 - - 11 26 -
K2CO3 CH3C(O)CH3 72 60 54 6 - - -
Cs2CO3 CH3C(O)CH3 72 52 10 42 - - -
Na2CO3 CH3CN 20 56 - - 51 - 5
K2CO3 CH3CN 20 51 44 7 - - -
Cs2CO3 CH3CN 20 73 20 53 - - -
NH
SOO O O
S SS
H2C
CO
H
NO2
CONH
CH2
NO2
H
NH
SOO O O
S SS
H2C
CO
H
NO2
CONH
CH2
NO2
CONH
CH2
NO2
SOO O O
S SS
HCONH
CH2
NO2
H H SO
H
NH
SO O
S
H2C
CO
H
NO2
O
H2C
NH
NO2
O C
S O OS
H
CONH
CH2
NO2
NH
OH2C
CO
NO2
SO
CONH
CH2
NO2
SS
Reaction of BrCH2C(O)NHC6H4NO2 with p- tertbulylthiacalix[4]arene
1 2 3 4 5
Effect of binding sites preorganizationon calixarene platform
0
20
40
60
80
100E, %
S
OCH2CNEt2
O 4
Cone, paco, 1,3-alternate;Li, Na, K, Cs
Δ lg K ≈ 6-10S
OCH2C(O)NEt2 OCH2C(O)NEt2
2
1
cone-1paco-11,3-alt-1
Li+Na+
K+ Cs +
0
1
2
3
4
5
6
Macrocycle conformation effect
The extraction constants of alkali metal ions by conformers I and II.
Cone
SOO O O
S SS
O RO ROROR
SO
OOSS
OS
ORO R
O
O
R
R
Partial Cone
R R
R
O
O
O
OS S
O
O
OSS
R O
1,3-Alternate
I – R= Ph; II – R= NEt2
O
O
PhCs+
O
Ph O
O
PhO
O
Ph O
Cs+
O
PhO
O
PhO
O
Ph O
O
PhO
O
PhO
O
PhO
O
OPh
O
Ph O
Li+Li+
O
PhO
O
PhO
O
Ph O
O
Ph OLi+
O
PhO
O
PhO
O
O
PhPh
O
OLi+
Li+Li+
Li+
O
PhO
O
PhO
O
OPh
O
Ph O
Li+Li+
O
PhO
O
PhO
O
Ph O
O
Ph OLi+
O
PhO
O
PhO
O
O
PhPh
O
OLi+
Li+Li+
Li+
O
O
PhCs+
O
Ph O
O
PhO
O
Ph O
Cs+
O
PhO
O
PhO
O
Ph O
O
PhO
O
PhO
O
PhO
O
OPh
O
Ph O
Li+Li+
O
PhO
O
PhO
O
Ph O
O
Ph OLi+
O
PhO
O
PhO
O
O
PhPh
O
OLi+
Li+Li+
Li+
O
PhO
O
PhO
O
OPh
O
Ph O
Li+Li+
O
PhO
O
PhO
O
Ph O
O
Ph OLi+
O
PhO
O
PhO
O
O
PhPh
O
OLi+
Li+Li+
Li+
Complexes stoichiometry of I (R= CH2COPh)
Log Kex
1
2
3
4
Р 1
Р 2
Р 3
cone-2paco-21,3-alt-2
Li+ Na+K+ Cs +
0
2
4
6
8
10
12Log Kex
NH
3a3b3c
HNNH
HN
NHHN
HNNH HN
HN
NHNH
3 4 0 3 6 0 3 8 0 4 0 0 4 2 0 4 4 0 4 6 0 4 8 0 5 0 00
2 0
4 0
6 0
8 0
1 0 0
1 2 0 3 b 3 b + F -
3 b + C l-
3 b + B r-
3 b + J -
Fluo
resc
ence
Inte
nsity
, r.u
.
W a v e le n g th , n m
340 360 380 400 420 440 460 480 5000
50
100
150
200
3c 3c +F-
3c + Cl-
3c + Br-
3c + J-Fl
uore
scen
ce In
tens
ity, r
.u.
Wavelength, nm
340 360 380 400 420 440 460 480 5000
20
40
60
80
100
3a 3a +F -
3a + C l-
3a + B r-
3a + J-
Fluo
resc
ence
inte
nsity
, r.u
.
W ave length , nm- C(O)Naphtyl
F- Cl- Br- I-
350 420 350 420 350 420 350 420
3a ↑ ↑ ↑ ↑ - - ↓ ↓3b ↑ ↓ ↑ ↓ - ↓ ↓ ↓3c ↓ - - ↓
Array of fluorescent chemosensors for molecular recognition of halide anions
TransfectionTransfection DNADNA into theinto the cells by synthetic receptorscells by synthetic receptors
DNA
Calixarenes
Nanoparticles size (nm) /Polydispersity
Free ligand Li+ Ag+
Cone-5 - - 84 / 0.18
Cone-6 - 143 / 0.19 153 / 0.08
Paco-5 - - 134 / 0.16
Paco-6 - - 131 / 0.17
Alternate -5 - - 140 / 0.19
Alternate -6 - - 141 / 0.23
Extraction dataC (Меn+) = 0,1M, C(L) =10-4 - 2.5*10-3 M, С(Pic-) = 2.3*10-4 M
Li+ Ag+
n LogKex E% n LogKex E%
Cone-5 0.8 3.3 61 0.7 4.1 79
Cone-6 1.9 8.4 100 1.1 6.1 99
Paco-5 0.6 2.0 22 1.5 8.4 68
Paco-6 1.0 4.5 81 1.6 8.2 100
Alternate -5 0.6 2.0 16 2.0 9.9 98
Alternate -6 0.8 3.3 53 1.9 9.8 100
29
R
O
OO
O
RRR
S SOOO O
S S
RR O
O
O
O
R
R
SO
S SO OOS
RR
O O
OO
O
RR
S SO
O
OS
SR= N O
R= N
5
6
Cone Paco
1,3-Alternate
Aggregation effects at the complex formation with tetra-amides (DLS method)
30
3 hours
28 hours+ Ag+HNHN O
O
O
O
HN
NH
SO
S SO OO
S
Nanoparticles size distribution of Ag complex in CH2Cl2
Paco-7
C OHN
C
S SO
O
OSS
O
CONH
C OHN NH
O
CH2 H2C
CH2H2C
SEM nanoparticles image of Ag(I) complex in CH2Cl2
31
1,3-alt - 10
cone 1,3-alternate partial cone 1,2-alternate
- Binding sites: -COOH; -C(O)NR2; -CN; -Pyr; etc...
ORS SS
ROOR
OR
SS
OROR
ORORS SS S
OR
OR
ORSS
ORS
ROSS
OR OR
ORS S
Design of tectons for MOFs
1D
3D
2D
M/L=1/1 (nontubularsystem)
M/L=2/1 (tubular system)
M/L=1/1
M/L=2/1
Collaboration with M.W.Hosseini
Strategies of MOFs formation on the basis of 1,3-alternate
Preorganized calixarene ligands (1,3-alternate)
R
Y
* S*
4
R = t-Bu; H
R
* S*
O
C
N
n4
R
* S*
O4
C
N
R
* S*
O
NH2
n4
R
* S*
O4
O NR2
R
* S*
O
n4
O OH
X-Ray structure of the synthesized
calixarene ligands
2 31
X – non coordinating anion PF6
-, SbF6-, BF4
-
(C56H68N4O4S4Ag)(PF6)·2(CH2Cl2)
1D structure of (3-cyanopropoxy)-p-tert-butylthiacalix[4]arene with silver ion
Infinite linear 1D- structure, M/L=1/1
2
S
O(CH2)3CN 4
·AgX
Space group P2, Z = 1
Distorted tetrahedron
25,77 Å
Structure of decanuclear cluster of AgNO3 with (p-cyanobenzyloxy)-p-tert-butyl-thiacalix[4]arene
Space group P42/n, Z = 4The 1D arrangement along the c axis
The solid-state structure of clusters Ag10
Distance (Å)
Ag1-Ag2 3.568
Ag1-Ag3 3.854
Ag2-Ag3 5.380
Ag1-S 2.527
Ag2-S 2.654
Ag1 - pentacoordinated with a NSO3 environment
Ag2 – heptacoordinated with a SO6 environment
Ag3 - tetracoordinated with O4 environment
vertices of a tetrahedron
summits of the basal plane of the octahedron
apicalpositions
1,3 nm
1,3 nm
ТСА
The arrangement of the decanuclear cluster in the (001) plane
Acknowledgment
Scientific teamin KSU
Prof. I.I.StoikovDr.O.A.MostovayaDr. L.S.YakimovaA.Yu.ZhykovS.A.ZhykovaE.A.YushkovaE.A. Zaikov
GrantsRussian Foundation for Basic ResearchRussian Academy of Sciences Ministry of Education and Sciences RF CRDF
Collaborators
Prof. Ya.Z.VoloshinProf. M.W.HosseiniProf. R.R.AmirovProf. A.R.MustafinaProf. G.A.EvtyuginDr. E.E.StoikovaDr. A.T.Gubaidullin
Scientific team in IOPC
Dr. S.E.SolovievaDr. E.A.PopovaDr. S.R.KleshninaDr. M.N.KozlovaDr. L.M.PilishkinaA.A.Tuyftin
Academician A.I.Konovalov