Download Carboxylated Adamantylcalixarenes

Moscow State University
Chemistry Department
Carboxylated Adamantylcalixarenes
V. Kovalev
1
MSU, Laboratory of Macrocyclic Receptors
MAIN TOPICS:
 ADAMANTYLCALIX[4]ARENES CARBOXYLATED
AT THE LOWER RIM
 ADAMANTYLCALIX[4,6]ARENES CARBOXYLATED AT THE
UPPER RIM
 CONJUGATES OF CARBOXYLATED
ADAMANTYLCALIX[4,6]ARENES WITH AMINO ACIDS
 ADAMANTYLTHIACALIX[4]ARENES CARBOXYLATED AT
THE UPPER RIM
2
MSU, Laboratory of Macrocyclic Receptors
 ADAMANTYLCALIX[4]ARENES CARBOXYLATED
AT THE LOWER RIM
3
MSU, Laboratory of Macrocyclic Receptors
1.1. CALIX[4]ARENES CARBOXYLATED AT THE LOWER.
X
O
X
X
O
OO
O O
O
O
O
X
X
X
O OO O
R
R
O
OH
HO
X
1, X = OEt
2, X = OH
3, X = NEt2
4: X = H, t-Bu; R = CH3, CH2CONEt2,
R+R = (CH2CH2O)3CH2CH2
R
R
R
CH2 4
CH2 4
CH2 4
O
O
(CH2)4
NH+ C5H11
O
CO25
X
O
(CH2)n
NX
OH
6, R = H, tert-Bu;
X = H, C5H11
O
N
H
OH
O
7, R = H, tert-Bu
4
MSU, Laboratory of Macrocyclic Receptors
1.2. COMMON STRATEGY OF THE LOWER RIM CARBOXYLATION
OF CALIX[4]ARENES .
R
R
HOCH2 4
CH2 4
O
O
R
R
R
R
R
1. Activation
2. Y-
CH2 4
O
for X = OEt
X
O
O
OH
O
X = OEt, NR2
Y
Y = NR2
HO HO OH
OH
R = H, t-Bu
R
R
R
X
R
R
O
OY
HO-
O
OH
O
X = OEt, NR2
2
2
2
O
R
X
OY
for X = OEt
O
Y = CH2COOEt, CH2CONEt2
HO
O
for X = OEt
Y = CH2COOEt2
5
MSU, Laboratory of Macrocyclic Receptors
1.3. ADAMANTYLCALIX[4]ARENES CARBOXYLATED AT THE
LOWER RIM .
CH2
HO HO OH
OH
R
R
L1, X = OEt, OH, NEt2
O
X
O
R
4
R
R
2
HO HO OH
OH
R = H, t-Bu, Ad
R
R
O
N
OH
O
R
2
OH
HN O
X
L2, X = Alkyl, 1-adamantyl
3-Y-1-adamantyl,
Y - functional groups
6
MSU, Laboratory of Macrocyclic Receptors
1.4. p-(1-ADAMANTYL)CALIX[4]ARENE TETRACARBOXYLIC
ACID AND ITS DERIVATIVES. .
Ad
Ad
Ad
BrCH2CO2Et,
K2CO3, aceton
CH2
OH
1. NaOH,
CH2
O
4
O
CH2
4
O
2. HCl
4
OH
O
9, 93%
OEt
8, 77%
Ad
R
NHR'R''
SOCl2, C6H6
CH2
O
O
4
Cl
CH2
O
O
X
4
10, X = NEt2,
88%
N(CH2)5, 90%
7
MSU, Laboratory of Macrocyclic Receptors
1.5. COMPLEXATION OF TETRADIETHYLAMIDE OF
AdC4A CARBOXILIC ACID WITH Sr(Pic)2.
Ad
CH2
Ad
CH2
4
O
O
4
+ Sr(Pic)
2
n-C3H7OH/CHCl3
CH2
O
.
Sr(Pic)2
NEt2
O
NEt2
O
NEt2
O
10
11
Some characteristic signals of 1H NMR spectra
of complexated and free ligands
RR
R
OO
OO
R = Ad
complex free ligand
R
tert-Bu
complex free ligand
H
7.18
(6.84)
7.19
(6.81)
Heq
3.36
(3.23)
3.32
(3.23)
4.20
(5.32)
4.21
(5.34)
3.50
(3.36)
3.50
(3.36)
Hax
2+
Et2N
Sr
O
Et2N
O
O
O
N CH2
NEt2
CH3
CH3
MSU, Laboratory of Macrocyclic Receptors
8
4
1.6. AdC4A SELECTIVELY CARBOXYLATED
AT THE LOWER RIM.
OH +
R
N
CF3COOH (5-10 equiv)
NHCOR
20-80oC, 7-15h
X
X
R
R
40-90%
R
ClCH2CN, K2CO3,
NaI, aceton
CH2
OH
4
CH2
OH
O
2
N
R
12, t-Bu, 71%
13,
H, 74%
14, Ad, 81%
9
MSU, Laboratory of Macrocyclic Receptors
1.7. AdC4A SELECTIVELY CARBOXYLATED
AT THE LOWER RIM
R
R
X
R
R
+
NC
OH
O HO O
OH
X=H
X = 4-MeC6H4
X = iso-Pr
X = CH2COOH
CN
12, R = tert-Bu
13, R = 1-adamantyl
CF3CO2H
20-70oC
R
R
R
R
44-76%
O
O HO O
HO
O
HN
X
NH
X
15, X = H,
R = tert-Bu
16, X = 4-MeC6H4, R = tert-Bu
17, X = CH2COOH, R = tert-Bu
18, X = H,
R = 1-Ad
19, X = iso-Pr,
R = 1-Ad
10
MSU, Laboratory of Macrocyclic Receptors
1.8. THE ALKYLATION OF CALIXARENE NITRILES IN
TRIFLUOROACETIC ACID (TFA).
CH2
OH
O
CH2
Ph2CHOH, TFA
OH
2
HN
C
H
N
12
O
O
20
11
MSU, Laboratory of Macrocyclic Receptors
2
1.9. ADAMANTYLATION OF 1,3-DICYANOMETHOXY-p-HCALIX[4]ARENE IN TFA
1-Ad+
1-Ad+
B
H
OH
C
H
COOH
CH2
OH
H
H
CF3COOH
CH2
OH
2
O
HN
O
N
1-Ad+
2
1-AdOH (4.1 equiv.)
CF3COOH
Ad
H
A
CH2 2
O
OH
O
HN O
Ad
O
OH
21, 69%
22, 19%
12
MSU, Laboratory of Macrocyclic Receptors
1.10. X-RAY STRUCTURE OF 5,17-DI(1-Ad)-26,28-DI[N-(1-Ad)CARBOMOYLMETHOXY]CALIX[4]ARENE.
Empirical formula
Formula weight
Temperature
Crystal system,
space group
Unit cell dimensions
Volume
Z, Calculated density
C96 H116 N2 O6
1393.91
110(2) K
MONOCLINIC, C2/C
a = 60.018(8)A
b = 10.9904(14)A
c = 24.777(3) A
15698(3) A3
8, 1.180 Mg/m^3
Analysis of Potential Hydrogen Bonds:
… Acceptor
N(1) – H(1A) … O(3)
N(1) – H(1A) … O(4)
O(3) – H(3A) … O(6)
O(5) – H(5A) … O(4)
Donor – H
distances
angles
3.024(3)
164.03
2.663(3)
110.84
2.715(3)
178(3)
2.768(2)
173(3)
13
MSU, Laboratory of Macrocyclic Receptors
 ADAMANTYLCALIX[4,6]ARENES
CARBOXYLATED AT THE UPPER RIM
14
MSU, Laboratory of Macrocyclic Receptors
2.1. FULL ADAMANTYLATION OF p-H-CALIX[4, 6]ARENES BY
CARBOXYLATED ADAMANTANOLS
OH
CH2
OH
+
R
n
+ CF3COOH
O
O
OH
HO
O
HO
OH
CH2 n
OH
CH2
n = 4, 6
OH
n
CH2
OH
Yields 90-100%
15
MSU, Laboratory of Macrocyclic Receptors
n
2.2. SELECTIVE ADAMANTYLATION OF p-H-CALIX[4, 6]ARENES WITH CARBOXYLATED ADAMANTANOLS
HOOC
COOH
O2N
O
O2N
OH
HO
NO2
O
O
O
i
i
ii
OH
OH HO HO
OH
OH HO HO
NO2
i: 3-R-1-AdOH, CF3COOH, reflux; ii: NaOH / EtOH / H2O
R
i
OH
OH
OH
2
OH
R =
OH
CH2COOH
OH
2
OH
16
COOH
MSU, Laboratory of Macrocyclic Receptors
2.3. UPPER and LOWER RIM METHYLATION OF CARBOXY
LATED DAMANTYLCALIX[6]ARENES
O
O
OH
OH
6
(MeO)2SO2 / NaH
OH
6
6
O
O
O
2
NaOH/EtOH/H2O
3a
OH
OH
O
2a
OH
O
O
1a
OH
O
O
5a
O
O
O
4a
2
O
O
OH
O
2
6a
17
MSU, Laboratory of Macrocyclic Receptors
2.4. UPPER RIM MODIFICATIONS OF CARBOXYLATED
ADAMANTYLCALIX[6]ARENES.
O OH
NR1R2 = Et2N
O NR R
1 2
N
O Cl
6
OR
N
H
N
1a, R = H
5a, R = Me
O
O
O NH
2
CN
O OMe
O OH
5f
5g
OH
OR
OR
OR
O
2
2a, R = H
6a, R = Me
18
MSU, Laboratory of Macrocyclic Receptors
2.5. CONFORMATIONAL PROPERTIES OF
ADAMANTYLCALIX[4]ARENES
O
SO2Me
O
OH
OMe
O
OH
OH
4
OH
4
OH
4
OH
4
OH
R
n
SOLVENT
TC, C
G*, KCAL/MOL
1-Adamantyl
4
Chloroform
53
15.7
3-MeSO2Ph-1-Ad
4
Chloroform
60
15.9
3-HOOCCH2-1-Ad
4
Tetrachloroethane
95
17.5
3-MeOOCCH2-1-Ad
4
Chloroform
57
15.8
3-HOOC-1-Ad
4
DMSO
30
19
4
2.6. CONFORMATIONAL PROPERTIES OF
ADAMANTYLCALIX[6]ARENES
O
SO2Me
OH
6
OH
6
OH
O
OH
6
OH
OMe
6
Coalescence Temperatures For The Conformational Inversion
Of The Adamantylcalix[6]arenes.
R
n
SOLVENT
TC, C
G*, KCAL/MOL
tert-Butyl
6
Chloroform
11
13.3
tert-Octyl
6
Chloroform
13
13.6
1-Adamantyl
6
Chloroform
12
-
3-MeSO2Ph-1-Ad
6
Chloroform
25
-
3-HOOCCH2-1-Ad
6
Chloroform
60
20
MSU, Laboratory of Macrocyclic Receptors
2.7. 1H NMR SPECTRUM of p-(3-CARBOXYMETHYL-1ADAMANTYL)CALIX[6]ARENE in CDCl3 at 298 K.
21
MSU, Laboratory of Macrocyclic Receptors
2.8. METHYLENE PARTS OF 1H NMR SPECTRA
of MONBENZYLATED P-TERT-BUTYL- (A) and ADAMANTYL(B) CALIX[6]ARENE IN CDCl3
Ha,b
Hc,d
He,f
22
MSU, Laboratory of Macrocyclic Receptors
2.9. METYLENE PARTS OF 1H NMR SPECTRA OF CARBOXYLATED
CALIX[6]ARENES 1a, 2a, 2f, 4a and 6a (RT, CDCl3)
O OH
O OX
2a, X = Y = H
2f, X = CH3, Y = H
OH
6
OY
OY
OY
1a
2
4a, X = Y = CH3
6a, X = H, Y = CH3
1a
2a
2f
4a
6a
23
MSU, Laboratory of Macrocyclic Receptors
 CONJUGATES OF CARBOXYLATED
ADAMANTYLCALIX[4,6]ARENES
WITH AMINO ACIDS
24
MSU, Laboratory of Macrocyclic Receptors
3.1. PRINCIPAL STRATEGIES OF PEPTIDOCALIX[N]ARENE
SYNTHESES. UPPER AND LOWER RIM DERIVATIVES.
XOOC
HN
CO
COOH
ZHN
R
OC
NH2
H2N-CHRCOOX
COOH
a) N-linked peptidocalixarenes
R
NH
ZHN-CHRCOOH
OC
NH
R
COOX
NH2
HN
CO
R
NHZ
b) C-linked peptidocalixarenes
25
MSU, Laboratory of Macrocyclic Receptors
3.2. CONJUGATES OF CALIX[4,6]ARENES WITH AMINO
ACIDS.
N
H
O
O
NH
H
O
HN
R4
N
H
H
NH
HN
H
H
O
O
O
O
R3
H
N
O
NH
O O
R2
N
H
O
HN
O
N
H
R1
NH
HN
O
O
8
MeO
O
4
O H
OH
O
O O
OMe
O
HN
HN
AA1
AA3
AA2
AA4
O
O
O
O H
N
H
O
O
O
N
H
NH
H
N
O
O
OH
H
26
MSU, Laboratory of Macrocyclic Receptors
3.4. CONJUGATES OF ADAMANTYLCALIX[4,6]ARENES WITH
AMINO ACIDS. SYNTHESIS
OH
OH
O
HO
O
O
OH
O
OH
HO HO
OH
1a, R = H;
1b, R = CH2Ph
1. SOCl2
2. HCl NH2CHRCOOMe, Et3N
THF - H2O
OMe
MeO
MeO
O
O
R
R
NH
O
NH
O
O
R
HN
O
O
R
HN
O
OH
HO HO
OH
MSU, Laboratory of Macrocyclic Receptors
OMe
27
3.5. CONJUGATES OF AdC[4,6]A WITH AMINO ACIDS.
POTENTIOMETRIC MEASUREMENTS.
Membrane composition for carrier-based ISEs in wt %.
Membrane 1
Sensor agent, calixarene 1
1
Polymer matrix, PVC
66.0
Plastizer, o-NPOE
33.0
Ionoc additive, NaTPB
-
Membrane 2
1
65.7
32.9
0.4
Membrane 1
Membrane 2
150
200
150
Emf, mV
Emf, mV
120
90
60
30
100
50
0
-50
-100
0
-5
-4
-3
-2
-1
0
lg a (МE Phe)
-5
МЭ Ile
-4
-3
МЭ Tyr
-2
МЭ Phe
For linear section of the calibration curves
Slope (mV decade-1)
43±5 (Phe)
57±2 (Phe)
46±1 (Ile)
59±1 (Tyr)
MSU, Laboratory of Macrocyclic Receptors
-1
0
lg a (МE X)
28
3.6. CONJUGATES OF AdC[4,6]A WITH AMINO ACIDS.
WORKING CHARACTERISTICS OF THE MEMBRANE 2.
Potentiometric selectivity coefficients (log KPot) of the ISE 2 for ME Phe and Ile
in the presence of various interfering ions
Mg2+
Ca2+
ME Tyr ME Val ME Leu ME Ile
Li+
-1,1
-0,8
lg K pot (ME Ile/X)
lg K pot (ME Phe/X)
-1
-0,5
-0,6
-2
-3
-4
Na+
NH4+
K+
Cs+
Rb+
-2,4
-2,3
0
0
-3,9
-1
-2
-3
-3,2
-4
-3,6
-5
-5
-2,9
-4,3
-4,4
Effect of pH of the test solution on the potential response of the ME Phe.H+
ion-selective electrode
E, мВ
60
40
20
0
-20 0
pH
2
4
6
8
10
-40
-60
-80
29
MSU, Laboratory of Macrocyclic Receptors
 ADAMANTYLTHIACALIX[4]ARENES
CARBOXYLATED AT THE UPPER RIM
30
MSU, Laboratory of Macrocyclic Receptors
4.1. THE WAYS OF TC4A TRANSFORMATIONS.
NaO3S
Na3SO3 SO3Na
SO3Na
B+C
A
S S
S S
OH HO OH HO
S S
S S
OH HO OH HO
The high complexation ability
toward organohalogenes
C-S
SOSO
SO SO
O
O O O
CH3CH3
H3C H3C
1.76 A
D
B
SOn
SOSO
n
n
HHOO
OH
OH
SOn
n = 1, 2
C
SOSO
SO sO
OH HO OH HO
S S
S S
NH2 NH2 H N
NH22
31
MSU, Laboratory of Macrocyclic Receptors
4.2. TC[4]A MODIFIED AT THE UPPER RIM. LIT. DATA
R
R
S
OH
OHH O
OH
R
S
S
S
S
R
H
H
S
S
OH HOHO
OPr
OHHO
OPr
Br
R
1, R = t-Bu;
2, R = 1,1,3,3-tetramethylbutyl
3, R = H;
4, R = SO3Na
H
S
Br
S
S
R
5, R = H
6, R = Br
H
S S
HO
+
E+
E = NO2+, Br+, RCO+, CO+
32
MSU, Laboratory of Macrocyclic Receptors
4.3. THE BROMINATION 0F 1,3-DIPROPYLOXY-TC[4]A.
LIT. DATA
H
H
S
S
H
S
PrO HOHO
Br
H
H
S
S S
OH HOHO HO
Br
Br
H
S
Br
S S
OPr
S
PrO HOHO
Br
H
S
S
PrO HOHO
H
H
S S
OPr
Br
H
S S
OPr
33
MSU, Laboratory of Macrocyclic Receptors
4.4. FIRST SYNTHESIS OF ADAMANTYLATED TC[4]A
R
R
R
R
R = H, COOH
S
S
S
S
HO HO HO HO
OH
OH
S8, NaOH,
MeO(CH2O)4Me, 
S
4
7, 28%
34
MSU, Laboratory of Macrocyclic Receptors
4.5. X-RAY STRUCTURE OF p-(1-ADAMANTYL)-TC4A.
i) AdTC4A crystallized in the orthorhombic crystal system.
ii) the unit cell contained both AdTC4A and four CHCl3 molecules, one of
which was localized within the cavity of the host molecule;
iii) AdTC4A adopted a cone conformation;
iv) the average distance between two adjacent oxygen atoms
was 2.77 Ǻ as and in the case of t-BuTC4A.
35
MSU, Laboratory of Macrocyclic Receptors
4.6. ADAMANTYLATION OF p-H-TC[4]A .
OH
OH
S
i
S
ii
OH
S
4
4
i, AlCl3, toluene, phenol, 
4
ii, CF3COOH/CF3SO3H/,
CH2Cl2, phenol, 
OH
OH
OH
S
CF3COOH, LiClO4
reflux, 72 h
S
4
+
4
96%
36
MSU, Laboratory of Macrocyclic Receptors
4.7. SYNTHESIS OF THE AdTC[4]A CARBOXYLATED AT THE
UPPER RIM .
OH
OH
S
+
4
O
OH
CF3COOH, CF3SO3H,
reflux, 24h
OH
OH
S
4
THF/MeOH/H2SO4
reflux, 10h
S
4
OH
O
8, 96%
OMe
O
9, 58%
37
MSU, Laboratory of Macrocyclic Receptors
O
HO
ACKNOWLEDGEMENTS
OR
Participants:
FUNDS:
E. Shokova,
A. Motornay,
I. Vatsuoro,
A. Matveev,
I. Podolsky,
M. Kashapov
RFBR, Grant - 03-02-33353,
RFBR, Grant - 03-02-06254,
RFBR, Grant - 03-02-06252
38
MSU, Laboratory of Macrocyclic Receptors