Synthesis and 1H NMR complexation study of thiacalix[4]arene tetraacetates

Article abstract of DOI:10.1135/cccc20000757

Alkylation of thiacalix[4]arenes with ethyl bromoacetate led to high yields (≈60%) of corresponding tetraacetates in various conformations (cone, partial cone, 1,3-alternate) depending strictly on the carbonate (Na, K, Cs) used for the reaction. The complexation ability of new compounds was studied by ¹H NMR.

Full text of DOI:10.1135/cccc20000757

Thiacalix[4]arene Tetraacetates
757
SYNTHESIS AND 1H NMR COMPLEXATION STUDY
OF THIACALIX[4]ARENE TETRAACETATES
a4
Pavel LHOTÁKa1,*, Václav ŠŤASTNÝa2, Petra ZLATUŠKOVÁa3, Ivan STIBOR
,
b3
Veronika MICHLOVÁb1, Marcela TKADLECOVÁb2, Jaroslav HAVLÍČEK
c
and Jan SÝKORA
a
Department of Organic Chemistry, Prague Institute of Chemical Technology, Technická 5,
1
2
166 28 Prague 6, Czech Republic; e-mail: lhotakp@vscht.cz, stastnyv@vscht.cz,
3
4
zlatuskp@vscht.cz, stibori@vscht.cz
Department of Analytical Chemistry, Prague Institute of Chemical Technology, Technická 5,
b
c
1
2
166 28 Prague 6, Czech Republic; e-mail: michlovv@vscht.cz, tkadlecm@vscht.cz,
havlicej@vscht.cz
3
Department of Solid State Chemistry, Prague Institute of Chemical Technology, Technická 5,
166 28 Prague 6, Czech Republic; e-mail: sykoraj@vscht.cz
Received Jan uary 18, 2000
Accepted April 7, 2000
Dedicated to Professor Otakar Červinka on the occasion of his 75th birthday.
Alkylation of th iacalix[4]aren es with eth yl brom oacetate led to h igh yields (≈60%) of corre-
spon din g tetraacetates in various con form ation s (con e, partial con e, 1,3-altern ate) depen d-
in g strictly on th e carbon ate (Na, K, Cs) used for th e reaction . Th e com plexation ability of
n ew com poun ds was studied by 1H NMR.
Key w ord s: Calixaren es; Th iacalixaren es; Alkylation ; NMR spectroscopy; X-Ray diffraction ;
Com plexation ; Alkali m etal cation s.
Calix[n]aren es, th e well-kn own cyclic oligom ers of 4-substituted ph en ols
an d form aldeh yde, h ave drawn m uch atten tion durin g th e last decade1. Be-
cause of th eir sim ple on e-pot preparation , en ablin g large scale syn th esis,
an d due to th eir un ique m olecular fram ework with th e “sh apin g” an d “tun -
in g” possibilities, th ey becam e very popular as com plexation agen ts, m olec-
ular scaffolds an d/or useful buildin g blocks in th e con struction of m ore
elaborated m olecular system s in supram olecular ch em istry2.
Very recen tly, th e syn th esis of n ew type of calix[4]aren e bearin g four sul-
fur atom s in stead of m eth ylen e bridges h as been described3–9. Th e
tetraalkylated derivatives of so-called th iacalix[4]aren e 1 were foun d to pos-
sess in terestin g con form ation al beh aviour both in solution 10 an d in th e
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

758
Lhoták et al.:
solid state11. So far, th e 1,3-altern ate con form er was th e on ly isom er pre-
pared by direct alkylation of paren t calixaren es 1a an d 1b. Th erefore, th e
aim of our research was th e preparation of oth er con form ers, wh ich could
serve as a startin g m aterial an d suitable buildin g blocks for th e preparation
of m ore soph isticated structures.
X
X
X
X
S
S
S
S
O
1a, X = t-Bu
1b, X = H
O
O
O
H
H
H
H
Sin ce th e in troduction of four sim ple alkyl groups (m eth yl to butyl) led
on ly to th e 1,3-altern ate con form ation 11, we h ave attem pted usin g of ace-
tate groups wh ich sh ould possess a m uch h igh er com plexation ability an d,
con sequen tly, wh ich could serve as tem platin g un its in th e alkylation reac-
tion (Fig. 1). Th e alkylation of 1a an d 1b with an excess of eth yl brom o-
acetate12 was carried out in th e boilin g aceton e (3 days) in th e presen ce of
various alkali m etal carbon ates (Na2CO3, K2CO3, Cs2CO3). Un der th ese con -
dition s, th e expected tetraalkylated derivatives in th e form of im m obilised
con form ers were obtain ed (Sch em e 1). It was foun d th at th e crude reaction
m ixtures gen erally con tain th ree basic con form ers 2, 3 an d 4 (con e, partial
con e an d 1,3-altern ate, respectively), th e yields of wh ich stron gly depen d
on th e m etal used in th e reaction .
Th e alkylation of 1a carried out in th e presen ce of Cs2CO3 led to a h igh
yield (68%) of substan tially pure 1,3-altern ate con form er 4a, wh ich was
very sim ply isolated from th e crude reaction m ixture by precipitation 12 of a
ch loroform extract with m eth an ol. In th e m oth er liquor we h ave proved
S
S
S
S
S
S
S
S
S
S
S
O
S
O
O
O
O
O
O
O
O
R
O
R
O
R
O
R
R
R
R
R
R
R
R
R
C4
C2v
C2v'
FIG. 1
2ν–C2ν’ in tercon version of tetrasubstituted th iacalix[4]aren es
C
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Thiacalix[4]arene Tetraacetates
759
sm all am oun t of two oth er con form ation s, 2a an d 3a (in overall yields 0.5
an d 8%, respectively). Th e situation is sh own in Table I. Th e sam e reaction
with Na2CO3 gave con e derivative 2a (75%) as a m ain product again after
X
X
X
X
R
X
X
X
O
BrCH2COOEt
1a, 1b
+
M2CO3, acetone
S
S
S
S
S
S
S
S
O
O
O
O
R
O
R
O
O
R
X
R
R
R
R
2a, X = t-Bu
2b, X = H
3a, X = t-Bu
3b, X = H
X
X
R
R
O
O
M = Na, K, Cs
R = -CH2COOEt
+
S
S
S
S
O
4a, X = t-Bu
4b, X = H
O
X
X
R
R
SCHEME 1
TABLE I
Syn th esis an d isolation of th iacalix[4]aren e tetraacetates 2, 3 an d 4
Precipitate
Filtrate
Carbon ate Param eter
from 1a
from 1b
from 1a
from 1b
Na2CO3 overall yield , %
con ten t of con form ers,
75
65
1.5
8
2a/3a/4a
2b/3b/4b
2a/3a/4a
2b/3b/4b
%
100/0/0
87/13/0
55/0/0a
44/33/23
31/44/25
isolated, %
75/0/0
K2CO3
overall yield , %
69
58
14
11
con ten t of con form ers,
%
2a/3a/4a
6/80/14
0/62/0b
2b/3b/4b
3/79/18
0/48/0b
2a/3a/4a
50/50/50
2b/3b/4b
30/55/15
isolated, %
Cs2CO3
overall yield , %
68
70
8
8
con ten t of con form ers,
%
2a/3a/4a
0/0/100
2b/3b/4b
0/0/100
2a/3a/4a
0/85/15
2b/3b/4b
0/74/26
isolated, %
0/0/68
0/0/70
a
b
Isolated by repeated precipitation from a CH2Cl2–m eth an ol m ixture. Isolated by colum n
ch rom atograph y usin g th e wh ole reaction m ixture (precipitate an d filtrate com bin ed).
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

760
Lhoták et al.:
sim ple precipitation , wh ile th e m oth er liquor con tain s very sm all am oun ts
of all th ree con form ers 2a, 3a an d 4a (lover th an 1% of each ). Th e m ost
com plex situation was observed in case of K2CO3, wh ere th e precipitate
con tain s all th e th ree con form ation s 2a, 3a an d 4a in an approxim ate m o-
lar ratio of 6 : 80 : 14. Con sequen tly, th e partial con e con form er 3a was iso-
lated in 62% by colum n ch rom atograph y (silica gel) of th e wh ole reaction
m ixture. Th ese results are com parable with th e recen tly described syn th e-
sis12 of com poun ds 2a–4a. Neverth eless, we h ave an alysed th e reaction
m ixtures in m ore details12b sh owin g th e exact con ten ts of appropriate con -
form ers. Furth erm ore, our procedure yields th e proposed products with out
th e use of colum n ch rom atograph y12a (2a, 4a) on ly after a sim ple precipita-
tion from th e crude reaction m ixture. It en ables th e preparation of th e
above n oticed com poun ds in a large scale (up to 30 g of startin g th ia-
calixaren e 1a), as was proved by us.
Th e above facts in dicate th e crucial role of th e m etal tem plate in th e for-
m ation of appropriate con form ation s. Sim ilar effects are kn own from th e
ch em istry of “classic” calix[4]aren e, n everth eless, th e selectivity is n ot so
h igh , especially in th e case of 1,3-altern ate con form ation . It is well-kn own
th at th e tert-butylcalix[4]aren e gives with Cs2CO3 alm ost th e pure partial
con e isom er an d th e 1,3-altern ate is in accessible by direct alkylation 13. On
th e oth er h an d, th iacalix[4]aren e 1a gives sm ooth ly h igh yields of th is con -
form er. A possible explan ation can be based on th e fact th at th e size of
tem plate cation m atch th e size of th e cavity form ed by th iacalixaren e,
wh ich is obviously bigger th an th at in a “classic” calixaren e. Wh ile th e Na+
ion correspon ds to th e size of con e cavity an d can be accom m odated
am on gst four ester groups, th e Cs+ ion is clearly too big for such a bin din g
m ode. In stead, th e cesium cation prefers 1,3-altern ate con form ation wh ere
th e sterical repulsion is m in im ised. Th e potassium cation represen ts a kin d
of in term ediate situation .
It was sh own 13 in th e ch em istry of classical calix[4]aren e, th at th e rem ov-
in g of tert-butyl groups leads to dram atic ch an ges in th e con form ation al
preferen ces in th e alkylation reaction usin g eth yl brom oacetate. Th us,
tert-butylcalix[4]aren e gives with K2CO3 a m ixture of con e an d partial con e
derivatives in th e 96 : 3 ratio, wh ile calix[4]aren e un der th e iden tical con di-
tion s yields a com plex m ixture of con e, partial con e an d 1,3-altern ate con -
form ation s in th e 33 : 46 : 21 ratio. Con sequen tly, we h ave tested th e
beh aviour of de-tert-butylated th iacalix[4]aren e 1b in th e sam e reaction .
Surprisin gly, our results in dicate th e sam e type of th e con form ation al pref-
eren ces as observed for 1a (albeit n ot so pron oun ced) durin g th e alkylation
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Thiacalix[4]arene Tetraacetates
761
of 1b. Th us, with Na2CO3 used as a base, a m ixture of 2b an d 3b in th e
87 : 13 m olar ratio was obtain ed in 65% overall yield (after precipitation
with m eth an ol) wh ile K2CO3 gave a precipitate con sistin g of all th e th ree
con form ation s 2b/3b/4b in th e 3 : 79 : 18 ratio. A sim ple reprecipitation
did n ot lead to pure products. Hen ce, isom ers 2b an d 3b were isolated by
colum n ch rom atograph y on silica gel in 55 an d 48% yields, respectively.
Th e alkylation with Cs2CO3 gave m ixture of partial con e 3b an d 1,3-altern ate
4b com poun ds wh ich yielded pure 4b (70%) by reprecipitation from a
CH2Cl2–m eth an ol m ixture.
Th e 1H NMR spectra of com poun ds 2a, 3a an d 4a were m easured in
CDCl3. Th e sim plest con form er assign m en t is in th e case of partial con e de-
rivative 3a wh ere th e expected splittin g pattern can be foun d, such as th e
set of two sin glets an d two dublets (meta in teraction s) in th e arom atic re-
gion . Th e splittin g pattern of 2a an d 4a is th e sam e, sh owin g h igh sym m e-
try of both isom ers. Th erefore, for th e assign m en t of appropriate
1
con form ation , a H NOE experim en t (DPFGSE-NOE)14 was m easured. In th e
spectrum of 4a, we observed stron g in teraction s between th e O–CH2–CO
groups (4.61 ppm ) an d arom atic h ydrogen s (7.49 ppm ), wh ich are possible
on ly for 1,3-altern ate con form ation . Accordin gly, n o such in teraction was
obtain ed for 2a. An oth er in direct eviden ce for th e assign m en t of 2a an d 4a
is a 0.5 ppm differen ce (0.36 ppm for 2b an d 4b) between th e ch em ical
sh ifts of th e –CH2CO– groups: 5.17 versus 4.61 ppm . Th e sign ifican t
h igh -field sh ift for 1,3-altern ate is apparen tly caused by th e proxim ity of
th e above m en tion ed group an d th e arom atic system (m agn etic an isotropy
of arom atic rin g). Th e spectra of de-tert-butylated derivatives 2b–4b also
possess th e correspon din g splittin g pattern s. Th e in terestin g beh aviour was
observed with 2b wh ere broad sign als in th e arom atic part of th e spectrum
in dicate th e presen ce of an addition al dyn am ic process at room tem pera-
ture. As we foun d very recen tly, th is can be ascribed to th e C2ν–C2ν’ in ter-
con version between so called pin ch ed con e con form ation s of tetra-
substituted con e derivatives15 (Fig. 1). Th e apparen t C4 sym m etry of 2b ob-
served at am bien t tem perature (Fig. 2a, 28 °C) is in fact th e result of averag-
in g due to th e rapid equilibrium between th e two pin ch ed con e
con form ers. As obvious from Fig. 2, th e lowerin g of th e tem perature leads
to th e exten sive lin e broaden in g in th e 1H NMR spectrum (0 °C, Fig. 2b),
an d fin ally to th e form ation of two sets of sign als correspon din g to th e
lower C2v sym m etry of pin ch ed con e con form ation (–60 °C, Fig. 2d). Th e
relatively h igh coalescen ce tem perature of th is process (ca –10 °C) in dicates
th e m uch h igh er activation en ergy of pin ch ed con es in tercon version as
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

762
Lhoták et al.:
com pared with classical calix[4]aren es (in acetate derivatives th is process
h as n ever been observed)16.
Th e structure of 2b was also con firm ed by X-ray an alysis of sin gle crystal.
As sh own in Figs 3 an d 4, con e derivative possesses typical pin ch ed con e
con form ation with two opposite ph en yl rin gs facin g each oth er (in ter-
plan ar an gle 39°) in th e cavity an d two flatten ed rin gs (in terplan ar an gle
108°) orien ted outside th e cavity. As expected, th e cavity of 2b is som ewh at
bigger th an th at in th e correspon din g con e tetraacetate of “classic”
calix[4]aren e. Th us, th e distan ces between two n eigh bourin g sulfur atom s
(S1–S2) an d between two opposite sulfur atom s (S1–S3) are 5.48 an d 7.67 Å,
respectively, wh ile th e typical distan ces between correspon din g CH2 groups
in th e con e con form ation 17 of 5,11,17,23-tetra-tert-butyl-25,26,27,28-
tetrakis[(eth oxycarbon yl)m eth oxy]calix(4)aren e are 5.11 an d 7.16 Å.
28 °C
a
b
0 °C
c
–40 °C
–60 °C
d
8
7
6
5
4
3
2
1
ppm
FIG. 2
Tem perature depen den t 1H NMR spectra of 2b (CDCl3, 500 MHz)
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Thiacalix[4]arene Tetraacetates
763
C14
C34
C13
C25
C22
C15
C16
C33
C32
C24
C35
C26
C23
C12
S4
C3
C6
C36
C2
C1
C4
C11
O11
S1
C21
C5
S3
O21
C31
O31
S2
C17
C27
O1
C7
C8
C37
O28
C38
C18
O13
C28
O22
O33
O32
O3
O12
C29
C30
O2
C39
C19
C20
C9
C40
C10
FIG. 3
ORTEP drawin g of X-ray structure of 2b
Z
X
Y
0
FIG. 4
Molecular packin g of 2b
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

764
Lhoták et al.:
A com plexation study of 2a–4a reveals th at all n ovel com poun ds in teract
with alkali m etal cation s. Th e in teraction s were studied by 1H NMR spec-
troscopy (300, 400 or 500 MHz, CDCl3 : CD3CN is 4 : 1, v/v) usin g stan dard
NMR titration experim en ts, wh ere th e ligan d con cen tration was kept con -
stan t wh ile th e con cen tration of salts (picrates) was ch an ged to ach ieve at
least a twen ty-fold excess.
Th e titration experim en ts could be subdivided in to th ree gen eral groups:
(i) slow-exch an ge con dition s, (ii) fast-exch an ge con dition s an d (iii) in ter-
m ediate con dition s. Un der th e slow-exch an ge con dition s, two sets of sig-
n als were observed in th e spectra, assign able to th e com plexed an d
un com plexed ligan d. In all th e cases studied, th e form ation of on ly th e
1 : 1 com plexes was observed as in dicated by ch aracteristic doublin g of ap-
propriate sign als. Figure 5 sh ows th is situation after an addition of sodium
picrate to a solution of 2a at 298 K. Sim ilar beh aviour was also foun d for
th e 2a : K+ system at 230 K, wh ile at room tem perature, on ly un resolved
broad diffuse peaks were obtain ed, wh ich correspon ds to th e above-n oticed
item (iii).
All experim en ts carried out with 1,3-altern ate con form ation of 4a at
room tem perature also possessed typical features of in term ediate con di-
tion s: very broad, in sufficien tly resolved peaks, un acceptable for th e direct
in tegration . Hen ce, to ach ieve better resolution with 4a, m easurem en t at
lower tem peratures was used: Na+ (260 K), K+ (270 K), Rb+ (230 K) an d Cs+
a
b
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
ppm
4.0
FIG. 5
Partial 1H NMR spectrum of 2a (300 MHz, 298 K, CDCl3): a after addition of Na+Pic–, b free 2a
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Thiacalix[4]arene Tetraacetates
765
1
(230 K). Th e lower sym m etry of H NMR spectra of th e com plexes in dicates
an un sym m etrical com plexation , with th e m etal cation h eld by two acetate
un its at on e side of th e m olecule. An exam ple of th e com plex form ation for
th e 4a : Rb+ system is depicted in Fig. 6. In all th e above-m en tion ed m ea-
surem en ts, sim ple in tegration of appropriate sign als led directly to th e con -
cen tration of com plexed an d un com plexed th iacalixaren e species in th e
m easured solution . Th e correspon din g com plexation con stan ts were th en
obtain ed as an average value from several in depen den t m easurem en ts; th ey
are collected in Table II.
An addition of m etal (Li, Na, K, Rb) picrates in to a solution of partial
con e derivative 3a at room tem perature resulted in th e in duced ch em ical
sh ifts of sign als – a typical feature of th e fast-exch an ge con dition s. As fol-
lows from Fig. 7, an addition of NaPic to a solution of 3a in
a
CDCl3 : CD3CN (4 : 1, v/v) m ixture caused a visible sh ift of arom atic pro-
ton s in both calix[4]aren e subun its (≈75 Hz). Th e plot of th e in duced ch em -
ical sh ifts versus th e added m etal con cen tration led to com m on titration
curves correspon din g to th e form ation of th e 1 : 1 com plex. Th e
stoich iom etry of th e com plexation was also proved usin g stan dard Job’s plot
procedure (Fig. 8). Th e com plexation con stan ts un der th e fast-exch an ge
con dition s were com puted usin g n on lin ear-regression curve-fittin g pro-
gram ; th ey are collected in Table II. Regardin g th e absolute values of th e
free
complex
free
complex
complex
5.0
4.9
4.8
4.7
4.6
4.5
4.4
4.3
4.2
ppm
4.1
FIG. 6
Partial 1H NMR spectrum of 4a (CDCl3 : CD3CN is 4 : 1, v/v) after addition of Rb+Pic– (500 MHz,
230 K, CDCl3)
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

766
Lhoták et al.:
TABLE II
Com plexation con stan ts K (in m ol–1 dm 3) for m etal picrates in CDCl3 : CD3CN (4 : 1, v/v),
tem peratures (in K) are in dicated in paren th eses
Com poun d Li+
Na+
K+
Rb+
Cs+
2a
3a
4a
2b
3b
4b
>104
6 600 ± 1 100 320 ± 30
0a
(298)
0a
(298)
0a
(298)
(298)b
(298)c
(230)c
3 500 ± 1 500
7 040 ± 740
31 000 ± 5 000 >104
(298)b
(298)b
(298)b
(298)b
0a
(298)
5 500 ± 2 300
4 800 ± 200
8 500 ± 3 100 210 ± 30
(260)c
(270)c
(230)c
(230)c
0a
(298)
0a
1 120 ± 210
2 870 ± 690
0a
(298)
0a
(298)
0a
(298)
(298)b
(298)b
0a
(298)
0a
(298)
0a
0a
(298)
(298)
(298)
0a
(298)
100 ± 80
680 ± 160
1 590 ± 800
(298)b,d
(298)b,d
(298)b,d
a
b
c
No ch an ges were observed in th e 1H NMR spectrum . Fast-exch an ge con dition s. Slow-
d
exch an ge con dition s. CDCl3 : CD3CN (1 : 1, v/v).
90
80
70
60
50
40
30
20
10
0
0.000
0.001
0.002
0.003
0.004
0.005
–1
c(LiPic), mol l
FIG. 7
Typical titration curve of 3a with Li+Pic– (500 MHz, 298 K, CDCl3 : CD3CN, c(3a) = 1 · 10–4
m ol dm –3
)
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Thiacalix[4]arene Tetraacetates
767
com plexation con stan ts, Table II in dicates som e tren ds – each con form er
2a–4a possesses th e h igh est selectivity towards a specific cation , th e size of
wh ich depen ds on th e sh ape of th e calixaren e cavity. Wh ile th e con e con -
form er 2a sh ows th e h igh est selectivity to Li+ (K > 104 m ol–1 dm 3) an d Na+
(K = 6 600 m ol–1 dm 3), th e 1,3-altern ate 4a prefers m uch larger Rb+ cation
(K = 8 500 m ol–1 dm 3). Th e selectivity of th e m easured com plexation gen er-
ally correspon ds to th e preferen ces obtain ed in th e alkylation reaction s.
Quite a differen t situation was foun d for th e tetraacetates 2b, 3b an d 4b,
derived from de-tert-butylated th iacalix[4]aren e. In gen eral, th e com plex-
ation ability of th ese com poun ds is suppressed if com pared with th at of
tert-butyl derivatives 2a–4a. Th e con e derivative 2b in teracts on ly with Li+
(K = 1 120 m ol–1 dm 3) an d Na+ (K = 2 870 m ol–1 dm 3) cation s, wh ile th e ad-
dition of KPic did n ot in duced an y visible ch an ges in NMR spectra. In terest-
in gly, th e pin ch ed con e–pin ch ed con e in tercon version is in fluen ced by th e
presen ce of Na+. Th e addition of 1 equivalen t of sodium picrate to th e solu-
tion of 2b in CDCl3 : CD3CN (4 : 1, v/v) suppressed th e coalescen ce tem per-
ature of th is process, obviously due to th e fact th at th e C4 sym m etry is
stabilised by th e com plexation (Figs 9a, 9b sh ow th e situation at –40 °C).
Subsequen t lowerin g of th e tem perature led fin ally to th e slow-exch an ge
con dition s an d to th e separated sign als for th e com plex (C4 sym m etry) an d
th e pin ch ed con e con form ers (C2v sym m etry) at –80 °C, Fig. 9c. To th e best
of our kn owledge, th is is th e first exam ple of such an equilibrium observed
in th e wh ole calixaren e ch em istry.
14
12
10
8
6
4
2
0
0.0
0.2
0.4
0.6
0.8
1.0
c(calix)/[c(calix) + c(NaPic)]
FIG. 8
Job’s plot for th e 3a: Na+Pic– system (CDCl3 : CD3CN is 4 : 1, v/v, c = 2 · 10–3 m ol dm –3
)
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

768
Lhoták et al.:
Very un expected results were obtain ed for th e partial con e con form er 3b.
Under the conditions used for the m easurem ent (CDCl3 : CD3CN 4 : 1, 298 K,
500 Hz) n o ch an ges in spectra were observed after addition (up to 20 equiv-
alen ts) of th e correspon din g picrates (<10 Hz). Th is in dicates un preceden t-
edly low (if an y) com plexation con stan ts in th is case. Probably, th e partial
con e derivative 3b adopts such a con form ation th at does n ot en able efficien t
com plexation with spherical cations. 1,3-Alternate conform er 4b prefers larger
cations with the highest selectivity towards Cs+ (K = 1 590 m ol–1 dm 3).
In con clusion , th e alkylation of th iacalixaren es 1a an d 1b with eth yl
brom oacetate gives h igh yields of tetraalkylated products 2–4 im m obilised
in th e defin ed con form ation s, depen din g on th e cation used for th e reac-
tion . Th ese con form ers represen t valuable buildin g blocks for th e design of
n ovel th iacalixaren e-based receptors. Th e com plexation study revealed an
in terestin g beh aviour of th ese com poun ds, especially th e pin ch ed con e–
pin ch ed con e in tercon version of 2b an d its suppression by cation added.
The synthetic exploitation of new derivatives is currently under investigation.
a
–40 °C
b
–40 °C
c
–80 °C
9
8
7
6
5
4
3
2
1
0
ppm
FIG. 9
1H NMR spectra of 2b in CDCl3 : CD3CN (4 : 1, v/v): a free 2b (3 m ol dm –3), b th e sam e
sam ple after addition of NaPic (1 equivalen t), c sam ple as in b at lower tem perature
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Thiacalix[4]arene Tetraacetates
769
EXPERIMENTAL
Meltin g poin ts were determ in ed on a Boetius block (Zeiss Jen a, Germ an y) an d are n ot cor-
rected. Th e IR spectra (νm ax in cm –1) were m easured on an FT-IR spectrom eter Nicolet 740 in
KBr. 1H NMR spectra were obtain ed on a Bruker 400 in CDCl3 usin g TMS (δ 0 ppm ) as an in -
tern al stan dard. Ch em ical sh ifs are given in ppm (δ-scale), couplin g con stan ts (J) in Hz. Th e
purity of th e substan ces an d th e reaction courses were m on itored by TLC usin g Silufol an d
Alufol plates (Kavalier, Votice, Czech Republic). Colum n preparative ch rom atograph y was
carried out on a silica gel Merck (60/100).
Alkylation of Th iacalixaren e 1a. Gen eral Procedure
A m ixture of com poun d 1a (1.5 m m ol), an appropriate carbon ate (10 m m ol) an d eth yl
brom oacetate (20 m m ol) was stirred un der reflux in aceton e (20 m l) for 3 days. Th e reaction
m ixture was poured in to water an d extracted with ch loroform . Th e organ ic layer was
wash ed with water, dried over an h ydrous MgSO4 an d evaporated to dryn ess. Th e residue was
dissolved in CH2Cl2 (5 m l) an d precipitated from a great excess of m eth an ol (100 m l) to
yield crude products. Th e overall yields of th e precipitate an d th e product from th e filtrate
(after evaporation to dryn ess), togeth er with th e con ten ts of appropriate con form ers are col-
lected in Table I.
5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis[(ethoxycarbonyl)methoxy]-2,8,14,20-tetrathia-
calix[4]arene (cone) (2a). Carbon ate used: Na2CO3; yield 75%; m .p. 173–175 °C (m eth an ol–
CHCl3) (ref.12a: 180.0–180.6 °C, ref.12b: 165–167 °C). 1H NMR (CDCl3): 1.08 (s, 36 H, t-Bu);
1.27 (t, 12 H, J = 7.3, -CH2CH3); 4.20 (q, 8 H, J = 7.1, -CH2CH3); 5.17 (s, 8 H, O-CH2-COOEt);
7.28 (s, 8 H, H arom .). IR (KBr): 1 754, 1 730. For C56H72O12S4 (1 065.5) calculated: 63.13% C,
6.81% H, 12.04% S; foun d: 62.87% C, 6.73% H, 12.12% S.
5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis[(ethoxycarbonyl)methoxy]-2,8,14,20-tetrathia-
calix[4]arene (partial cone) (3a). Carbon ate used: K2CO3; isolated by colum n ch rom atograph y
on silica gel usin g a petroleum eth er–CHCl3 m ixture as an eluen t in 62% yield; m .p.
205–207 °C (eth yl acetate–CHCl3) (ref.12a: 212.0–212.8 °C, ref.12b: 202–204 °C). 1H NMR
(CDCl3): 1.04 (s, 18 H, t-Bu); 1.13 (t, 3 H, J = 7.1, -CH2CH3); 1.27 (t, 6 H, J = 7.1, -CH2CH3);
1.31 (s, 9 H, t-Bu); 1.32 (t, 3 H, J = 7.1, -CH2CH3); 1.42 (s, 9 H, t-Bu); 3.97 (q, 2 H, J = 7.1,
-CH2CH3); 4.15–4.30 (m , 6 H, J = 7.1, -CH2CH3); 4.64 (s, 2 H, O-CH2-COOEt); 4.69 (d, 2 H, J =
15.4, O-CH2-COOEt); 4.73 (s, 2 H, O-CH2-COOEt); 4.77 (d, 2 H, J = 15.4, O-CH2-COOEt);
7.01 (d, 2 H, J = 2.7, H arom .); 7.52 (d, 2 H, J = 2.7, H arom .); 7.54 (s, 2 H, H arom .); 7.85 (s,
2 H, H arom .). IR (KBr): 1 764. For C56H72O12S4 (1 065.5) calculated: 63.13% C, 6.81% H,
12.04% S; foun d: 63.03% C, 6.84% H, 11.94% S.
5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis[(ethoxycarbonyl)methoxy]-2,8,14,20-tetrathia-
calix[4]arene (1,3-alternate) (4a). Carbon ate used: Cs2CO3; yield 68%; m .p. 314–318 °C (eth yl
acetate–CHCl3) (ref.12a: 329.5–331.0 °C, ref.12b: >260 °C). 1H NMR (CDCl3): 1.24 (s, 36 H,
t-Bu); 1.27 (t, 12 H, J = 7.1, -CH2CH3); 4.21 (q, 8 H, J = 7.1, -CH2CH3); 4.61 (s, 8 H,
O-CH2-COOEt); 7.49 (s, 8 H, H arom .). IR (KBr): 1 768, 1 731. For C56H72O12S4 (1 065.5) cal-
culated: 63.13% C, 6.81% H, 12.04% S; foun d: 63.39% C, 7.01% H, 11.99% S.
Alkylation of Th iacalixaren e 1b. Gen eral Procedure
A m ixture of com poun d 1b (0.6 m m ol), an appropriate carbon ate (6 m m ol) an d eth yl
brom oacetate (12 m m ol) was stirred un der reflux in aceton e (15 m l) for 3 days. Th e reaction
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

770
Lhoták et al.:
m ixture was poured in to water an d extracted with ch loroform . Th e organ ic layer was
wash ed with water to n eutral pH, dried over an h ydrous MgSO4 an d evaporated to dryn ess.
Th e residue was dissolved in CH2Cl2 (2 m l) an d precipitated with m eth an ol (50 m l) to yield
crude products. Th e overall yields of th e precipitate an d product from th e filtrate (after
evaporation to dryn ess), togeth er with th e con ten ts of appropriate con form ers are collected
in Table I.
25,26,27,28-Tetrakis[(ethoxycarbonyl)methoxy]-2,8,14,20-tetrathiacalix[4]arene (cone) (2b ).
Carbon ate used: Na2CO3; isolated by reprecipitation from CH2Cl2–m eth an ol m ixture in 55%
yield; m .p. 116–117 °C (m eth an ol–CHCl3). 1H NMR (CDCl3): 1.26 (t, 12 H, J = 7.2,
-CH2CH3); 4.20 (q, 8 H, J = 7.1, -CH2CH3); 5.04 (s, 8 H, O-CH2-COOEt); 6.71 (brs, 4 H,
H-para); 7.00 (brs, 8 H, H-meta). IR (KBr): 1 754, 1 732. For C40H40O12S4 (841.0) calculated:
57.13% C, 7.79% H, 15.25% S; foun d: 57.57% C, 7.73% H, 15.22% S.
25,26,27,28-Tetrakis[(ethoxycarbonyl)methoxy]-2,8,14,20-tetrathiacalix[4]arene (partial cone)
(3b). Carbon ate used: K2CO3; isolated by colum n ch rom atograph y on silica gel usin g petro-
leum eth er–CHCl3 m ixture as an eluen t in 48% yield; m .p. 164–165 °C (eth yl acetate–
CHCl3). 1H NMR (CDCl3): 1.20 (t, 3 H, J = 7.1, -CH2CH3); 1.33 (t, 6 H, J = 7.2, -CH2CH3);
1.42 (t, 3 H, J = 7.1, -CH2CH3); 4.01 (q, 2 H, J = 6.6, -CH2CH3); 4.10 (s, 2 H, O-CH2-COOEt);
4.27 (q, 6 H, J = 7.1, -CH2CH3); 4.40 (q, 3 H, J = 7.1, -CH2CH3); 4.70 (s, 4 H, O-CH2-COOEt);
4.81 (s, 2 H, O-CH2-COOEt); 6.65 (t, 2 H, J = 7.7, H-para); 6.78 (d, 2 H, J = 8.1, H-meta); 6.90
(t, 2 H, J = 6.7, H-para); 7.15 (t, 2 H, J = 6.6, H-para); 7.46 (d, 2 H, J = 8.2, H-meta); 7.70 (d,
2 H, J = 7.7, H-meta); 7.96 (d, 2 H, J = 7.7, H-meta). IR (KBr): 1 755, 1 733. For C40H40O12S4
(841.0) calculated: 57.13% C, 7.79% H, 15.25% S; foun d: 57.07% C, 7.84% H, 15.04% S.
25,26,27,28-Tetrakis[(ethoxycarbonyl)methoxy]-2,8,14,20-tetrathiacalix[4]arene (1,3-alternate)
(4b). Carbon ate used: Cs2CO3; yield 70%; m .p. 194–195 °C (eth yl acetate–CHCl3). 1H NMR
(CDCl3): 1.39 (t, 12 H, J = 7.1, -CH2CH3); 4.34 (q, 8 H, J = 7.1, -CH2CH3); 4.68 (s, 8 H,
O-CH2-COOEt); 6.83 (t, 4 H, J = 7.7, H-meta); 7.60 (d, 8 H, J = 7.7, H-para). IR (KBr): 1 756,
1 731. For C40H40O12S4 (841.0) calculated: 57.13% C, 7.79% H, 15.25% S; foun d: 57.59% C,
7.81% H, 14.99% S.
X-Ray Measurem en t
X-Ray data for C40H40O12S4, M = 840.988 g m ol–1, orth orh om bic system , space group
P212121, a = 12.016(1), b = 16.245(1), c = 21.598(1) Å, Z = 4, V = 4215.8(4) Å3, Dc = 1.325
g cm –3, µ(CuKα) = 2.53 m m –1, crystal dim en sion s 0.08 × 0.15 × 0.4 m m . Data were m easured
at 293 K on an En raf–Non ius CAD4 diffractom eter with graph ite m on och rom ated CuKα ra-
diation . Th e structure was solved by direct m eth ods18 an d an isotropically refin ed by full-
m atrix least-squares on F (ref.19) to fin al R = 0.051 an d Rw = 0.05 usin g 2 956 in depen den t
reflection s (θm ax = 67.94°). Hydrogen atom s were foun d from th e expected geom etry; th ey
were n ot refin ed. Psi scan was used for th e absorption correction . Crystallograph ic data for
th e structure reported in th is paper h ave been deposited with th e Cam bridge
Crystallographic Data Centre as supplem entary publication num ber CCDC-139288. Copies of the
data can be obtained free of charge on application to CCDC, e-m ail: deposit@ccdc.cam .ac.uk.
The authors thank the Grant Agency of the Czech Republic for financial support of this work (grant
No. 203/97/0627).
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Thiacalix[4]arene Tetraacetates
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