DOKTORI ÉRTEKEZÉS
KIRÁLIS KORONAÉTEREKKEL KATALIZÁLT ENANTIOSZELEKTÍV SZINTÉZISEK
II. RÉSZ: MELLÉKELT KÖZLEMÉNYEK
Bakó Péter
Készült a
Budapesti Műszaki és Gazdaságtudományi Egyetem Szerves Kémiai Technológia Tanszékén
2000
A tézisek alapját képezó' közlemények [B1-B22]
B l .
Bakó P., Fenichel L., Tőke L., Davison B.E.:
Novel Azacrown Ethers Incorporating Sugars; Synthesis and Complex Formation.
J. Chem. Soc. Perkin Trans 1., 1990,1235-1238 B2.
Bakó P., Fenichel L., Tőke L.:
A Novel Diaza-Crown Ether and Cryptands from Glucopyranose and Their Complex-Forming Properties.
LiebigsAnn. Chem., 1990,1161-1164 B3.
Bakó P., Fenichel L., Tőke L.:
The Complexing Ability of Crown Ethers Incorporating Glucose J. Ind. Phenom., 1993,16,17-23.
B4.
Bakó P., Fenichel L., Tőke L., Davison B.E., Patel A.:
Elaboration of a Chiral 20-Crown-6 from a Glucofuranose Derivative and Its Complex with Alkali Cations.
Heteroatom Chem., 1994,5,415-419.
B5.
Bakó P. and Tőke L.:
Novel Monoaza- and Diazacrown Ethers Incorporating Sugar Units and Their Extraction Ability towards Picrate Salts.
J. Ind. Phenom., 1995,23,195-201.
B6.
Bakó P., Fenichel L. and Tőke L.:
Synthesis and Complex-Forming Properties of Crown Ethers Incorporating Glucuronic Acid Moieties.
J. Ind. Phenom., 1996,26,321-330.
B7.
Bakó P., Szöllősy Á., Bombicz P. and Tőke L.:
Asymmetric C-C Bond Forming Reactions by Chiral Crown Catalysts; Darzens Condensation and Nitroalkane Addition to the Double Bond
Synlett, 1997,291-292.
B8.
Bakó P., Szöllősy Á., Bombicz P. and Tőke L.:
Asymmetric Michael Addition of 2-Nitropropane to Chalcone Catalyzed by Chiral Crown Ethers Incorporating D-glucose Unit.
Heteroatom Chem., 1997,8, 333-337.
B9.
Bakó P., Kiss T., Tőke L.:
Chiral Azacrown Ethers Derived from D-glucose as Catalysts for Enantioselective Michael Addition.
Tetrahedron Lett., 1997,38,7259-7262.
BIO.
Tőke L., Bakó P., Keserű M.Gy., Albert M. and Fenichel L.:
Asymmetric Michael Addition and Deracemization of Enolate by Chiral Crown Ether Tetrahedron, 1998,54,213-222.
B l l .
Bakó P., Vizvárdi K., Bajor Z., Tőke L.:
Synthesis and application in asymmetric synthesis of azacrown ethers derived from D- glucose
Chem. Comm., 1998,1193-94.
B12.
Bakó P., Vizvárdi K., Toppét S., Van der Eycken E., Hoomaert G. J., Tőke L.:
Synthesis, Extraction Ability and Application in Asymmetric Synthesis of Azacrown Ethers Derived from D-glucose
Tetrahedron, 1998,54,14975-14988.
B13.
Bakó P., Nóvák T., Ludányi K., Pete B., Tőke L. és Keglevich Gy.:
D-Glucose-based azacrown ethers with a phosphonoalkyl side chain: application as enantioselective phase transfer catalysts
Tetrahedron:Asymmetry, 1999,10,2373-2380.
B14.
Bakó P., Czinege E., Bakó T., Czugler M., Tőke L.:
Asymmetric C-C bond forming reactions by chiral crown catalysts derived from D-glucose and D-galactose
Tetrahedron:Asymmetry, 1999,10,4539-4551 B15.
Nóvák T., Keglevich Gy., Imre T., Bakó P., Újszászy K., Ludányi K., Tőke L.:
Foszfonoalkil-oldalláncot tartalmazó azakoronák szintézise és komplexképzési tulajdonságainak vizsgálata.
Magyar Kémiai Folyóirat, 1999,1,16-21.
B16.
Keglevich Gy., Nóvák T., Bakó P., Újszászy K., Tőke L.:
Synthesis of Azacrown Ethers with P-Functionalized Side Chains Phosphorus, Sulfur and Silicon, 1999,147,159.
B17.
Keglevich Gy., Nóvák T., Bakó P., Újszászy K., Ludányi K., Tóth K., Tőke L.:
New Type of Lariat Ethes: Synthesis and Cation Binding Ability of Phosphonoalkyl- Azacrown Ethers.
J. Incl. Phenom., 1999,34,299-309.
B18.
Bakó P., Bajor Z., Tőke L.:
Synthesis of novel chiral crown ethers derived from D-glucose and their application to an enantioselective Michael reaction
J. Chem. Soc., Perkin Trans L, 1999,24,3651 -3655 B19.
Nóvák T., Bakó P., Dobó A., Ludányi K., Tőke L. és Keglevich Gy.:
Modification of D-glucose-based 18-crown-6 ethers by phosphorylation and phosphonylation
Heteroatom Chem., (elfogadva) B20.
Keglevich Gy., Nóvák T., Imre T., Bakó P., Tőke L., Újszászy K., Ludányi K.:
Synthesis and Cation Binding Ability of Azacrown Ethers with Phosphine or Phosphine Oxide Side Chain.
Heteroatom Chem., 1999,10,573-576 B21.
Nóvák T., Bakó P., Imre T., Keglevich Gy., Dobó A., Tőke L.:
Synthesis and Cation Binding Ability of the Phosphonoalkyl- and Phosphonoylalkyl Derivatives of Monoaza-18-crown-6
J. Incl. Phenom., (elfogadva) B22.
Bakó P., Bakó T., Szöllősy Á., Bisztray K , Nagy K., Tőke L.:
Chiral Azacrown Ethers Derived from D-Mannitol J. Incl. Phenom., (bekiildve)
1235
B1
J. CHEM. SOC. PERKIN TRANS. 1 1 9 9 0Novel Azacrown Ethers Incorporating Sugars: Synthesis and Complex Formation!
P é t e r B a k ó , László F e n i c h e l , a n d László T ő k e
Department of Organic Chemical Technology. Technical University, Budapest, Hungary B r u c e E. D a v i s o n
Department of Applied Chemistry and Life Sciences, Polytechnic of North London, Holloway Road, London N7 8DB
A z a c r o w n ethers derived from a m i n o - d e o x y sugars in w h i c h the sugar moiety forms part of the macro- cycle, or is pendant from it, have been synthesised and their c o m p l e x i n g ability towards cations compared.
Several syntheses of chiral diazacrown ethers in which a sugar unit forms part of the macrocyclic ring have been previously reported!""3 We have recently published details of the synthesis of chiral monoazacrown ethers with pendant sugars bonded to the nitrogen atom of a previously constructed macrocycle.4 We now report a synthesis of monoazacrown ethers by elabor- ation of sugar amines to give products in which the sugar forms part of the macrocyclic ring, and a comparative study of their complexing abilities with those of their pendant sugar counterparts.
The key intermediate, methyl 4,6-C-benzylidene-2-deoxy- 2-(Af-2-hydroxyethyl)amino-a-D-altropyranoside (1), was ob-
tained by ring-opening of methyl 2,3-anhydro-4,6-0-benzyI- idene-ot-D-allopyranoside (2) with ethanolamine.4 The Scheme shows the sequence of reactions employed to synthesise the macrocycles in which the sugars are incorporated. The products from cyclisation with the appropriate polyethylene bistosyl- ates5 were isolated and purified by preparative thin layer chromatography on Kieselgel 60 PF254 using toluene-metha- nol (5:1) as eluant. The 15-monoazatetraoxacrown-5 (3) was obtained as a crystaline material in 24% yield, while the 18- monoazapentaoxacrown-6 (4) resisted crystallisation. Since the yield of the 15-crown-5 (3) was affected by the undesired reaction of the bistosylate at the secondary amine, we carried
OMe
OMe rr\
,
NR OR1
j ^ V ^ O R ' 0 ^ 0 I
I Ph
(1) R'= R2= H r*- (5) R1 = H; R2= Et
I V| — (6) R1 = R2= Ac
(4)
Scheme. Reagents: i, H2NCH2CH2OH; ii, Ts0(CH2CH20)3Ts, Bu'ONa, Bu'OH, dioxan, 20 h; iii, Ts0(CH2CH20)4Ts, Bu'OK, Bu'OH, dioxan, 20 h; iv, LiAlH4, THF
t This communication is a reprinted version of the corresponding article which appeared in J. Chem. Soc., Perkin Trans. 1, 1989,2514. As the result of oversight in the Editorial Office, formulae (8)-(13) which should have appeared in this article were omitted. The Society apologizes for any inconvenience caused.
J C H E M . SOC. P E R K I N TRANS. I 1 9 9 0 1236
^
-0' 00 ^ 0 I
I Ph
(8)
OR OR
(9) R = H (10) R = Ac (11) R = Ts
OMe
(12)
HN
)
0
(13)
Table. Association constants (log K,) in CDCI3 at 22 °C log K, ( ± 0.05)
A
Compound Na + K + NH4H
(3) 4.73 4.54 4.45
(4) 5.18 4.84 4.90
(7) 4.96 4.64 4.56
(8) 5.84 5.45 5.53
(10) 5.41 4.98 4.78
(11) 6.02 5.42 5.27
(12) 6.11 5.61 4.98
(13) 6.03 5.52 5.72
o u t the synthesis on the (V-ethyl derivative (5), the preparation of which was accomplished by acetylation of (3) to yield the triacetyl derivative (6), followed by reduction with lithium a l u m i n i u m hydride. C o n d e n s a t i o n of (5) with triethylene glycol bistosylate resulted in a yield of 31% of the 15-(Ar-ethyl)- m o n o a z a t e t r a o x a c r o w n - 5 (7).
It was desired to c o m p a r e the complex-forming abilities of the a z o x a c r o w n s (5)—(7) with those of the crowns in which the sugar moieties are p e n d a n t ; to this end the benzylidene group of the previously described4 (V-altropyranosyl 15-monoazatetra- o x a c r o w n - 5 (8) was removed with hot ethanoic acid6 to yield the diol (9), f r o m which the derivatives (10) and (11) were p r e p a r e d by acetylation a n d tosylation respectively.
T h e T a b l e shows the association constants for sodium, p o t a s s i u m , a n d a m m o n i u m ions with the new crowns, together with those of the previously described (12)4 and (13),5 as m e a s u r e d in c h l o r o f o r m by the u.v. technique developed by C r a m .7 As expected, the unsubstituted 15-crown-5 gave the strongest complexes. W h e n the sugar is incorporated into the macrocyclic ring [ c o m p o u n d s (3), (4), and (7)] there is a reduction in the log K, values, b u t this is not so marked in the case of the p e n d a n t sugar crowns (8) and (10)—(12). The likely reason for these observations is an entropy effect due to the
relative rigidity conferred on the ring by the fused sugar moiety in (3), (4), and (7) and concomitant steric hindrance to the binding of the ion, effects which are absent in the p e n d a n t sugar types. A-Alkylation as in (7) predictably increases the log A", values for potassium and sodium ions by increasing the d o n o r ability of the nitrogen ligand. A comparison of log K, values for the substituted pendant sugar crowns (10) and (11) s h o w s t h a t the presence of acetyl groups produces poorer c o m p l e x a t i o n than the benzylidene derivative (8) while tosyl g r o u p s cause a relative increase. T w o possibilities are that there is additional bonding by the tosyl groups to the ion held in the cavity of the crown ether or that complexation is primarily to the tosyl g r o u p itself i.e. the complex is not of the classic crown ether type. T h e present work does not distinguish these two possibilities although the similarity of log K, values would suggest that the former is the most likely explanation.
Experimental
Monoazacrown Ethers (3), (4), and (7).—General procedure.
The hydroxyethylamino derivatives (1) or (5) (4.5 m m o l ) a n d sodium or potassium were dissolved in t-butanol (38 ml) u n d e r an atmosphere of argon and a solution of triethyleneglycol ditosylate or tetraethyleneglycol ditosylate (4.5 m m o l ) in dioxane was added during 3—4 h at 40 °C. T h e solution was cooled, the precipitated sodium or potassium tosylate removed by filtration, and the filtrate evaporated in vacuo. T h e residue was suspended in water (30 ml), washed with hexane (15 ml), and extracted with dichloromethane (3 x 20 ml). E v a p o r a t i o n of the extracts gave a residue (1.8—2.3 g) which was subjected to preparative thin layer c h r o m a t o g r a p h y using t o l u e n e - m e t h a n o l (10:2) as eluant.
\5-Monoazatetraoxacrown-S (3) was obtained as crystals from ethanol (0.476 g, 24%), m.p. 54—56 C, [<%]£> 31.5° (c 1, C H C l j ) (Found: C, 59.9; H, 7.5; N, 3.2%; A /+, 439. C2 2H3 3N 08
requires C, 60.14; H, 7.52; N, 3.19%; M+, 439); 8(CDC13) 2.22 (1 H, br, s N H ) , 2.73—3.0(2 H, q, N C H2) , 3.15 (1 H, d, 2-H), 3.41 (3 H, s, O C H3) , 3.50—4.40 (19 H, m, 8 x C H2, 3 x C H ) , 4.60 (1 H, d, 1-H), 5.59 (1 H, s, P h CH), and 7.20—7.52 (5 H, m, Ph).
1237 J. CHEM. SOC. PERKIN TRANS. 1 1 9 9 0 1 %-Monoazapentaoxacrown-(t (4), oil, (0.543 g, 25%),
26.6° (c 0.96, CDClj) (Found: C, 58.9; H, 7.6; N, 2.95%; M *, 483.
C24H3,NO<, requires C, 59.63; H, 7.66; N, 2.90%; M*, 483);
8(CDC13) 2.28 (1 H, s, NH), 2.73—3.11 (3 H, m, NCH2, 2-H), 3.43 (3 H, s, OCHj), 3.50—4.40 (23 H, m, 10 x CH2,3 x CH), 4.56 (1 H, d, 1-H), 5.56 (1 H, s, PhCW), and 7.35—7.61 (5 H, m, Ph).
(N-Ethyl)-15-monoazatetraoxacrown-S (7), oil, (0.658 g, 31%), Oft0 56.0° (c 0.97, CHCIj) (Found: C, 61.6; H, 7.95; N, 2.95%;
M+,467. C2 4H3 7N08 requires C, 61.67; H, 7.92; N, 3.00%; M*, 467); 8(CDC13) 1.05 (3 H, t, CH3), 2.40—2.92 (4 H, m, 2 x NCH2), 3.08 (1 H, d, 2-H), 3.36 (3 H, s, OCH3), 3.50—4.40 (19 H, m, 8 x CH2, 3 x CH), 4.65 (1 H, d, 1-H), 5.54 (1 H, s, PhC//), and 7.25—7.62 (5 H, m, Ph).
References
1 M. Pietraszkiewicz and J. Jurczak, J. Chem. Soc., Chem. Commun..
1983, 132; M. Pietraszkiewicz, P. Salanski, and J. Jurczak. ihid.. 1983.
1184.
2 M. Pietraszkiewicz and J. Jurczak, Tetrahedron, 1984, 40, 2967; M Pietraszkiewicz, P. Salanski, and J. Jurczak, ibid., 1984,40, 2971.
3 P. Bako, L. Fenichel, and L. Toke, Acta Chim. Acad. Sci. Hung., 1984.
115,323.
4 G. Toth, W. Dietrich, P. Bakó, L. Fenichel, and L. Tőke, Carbohvdr.
Res., 1987,168, 141.
5 H. Maedaand Y. Nakatsuji. 7. Chem. Soc., Chem. Commun., 1981,471.
6 R. L. Whistler and M. L. Wolfram, 'Methods in Carbohydrate Chemistry,' vol. I (Academic Press. N.Y., 1963) p. 214.
7 S. S. Moore, T. L. Tarnowski, M. Newcomb, and D. J. Cram, J. Am.
Chem. Soc., 1977,99,6398.
Acknowledgements
The authors gratefully acknowledge the financial assistance of Paper 9/03808F
the International Department of the Technical University, Received 12th July 1989
Budapest and the British Council. Accepted 1 Ith September 1989
I
i
P. Bakó, L. Fenichel, L. Töke 1161
A Novel Diaza-Crown Ether and Cryptands from Glucopyranose and Their Complex-Forming Properties
Péter Bakó, László Fenichel, László T ő k e *
Department of Organic Chemical Technology, Technical University of Budapest, Műegyetem, P. O. Box 91, H-1521 Budapest
Received April 18, 1990
Key Words: C r o w n ether derivatives / C o m p l e x f o r m a t i o n c o n s t a n t s
C h i r a l diaza-crown ether 6 and c r y p t a n d s of t y p e [2.2.2] (9), c o n t a i n i n g o n e glucopyranoside unit, h a v e b e e n p r e p a r e d . T w o m e t h o d s are described for t h e synthesis of 9. T h e n e w
c r y p t a n d 12 c o n t a i n i n g t w o g l u c o p y r a n o s i d e units h a s also b e e n p r e p a r e d . T h e association c o n s t a n t s (Ka) of t h e s e com- p o u n d s with Li, Na, K and N H4 cations h a v e b e e n m e a s u r e d .
S u g a r derivatives are c h e a p s t a r t i n g m a t e r i a l s for the syn- thesis of chiral c r o w n c o m p o u n d s1 - 1 7 ).
C r o w n e t h e r s c o n s i d e r a b l y c h a n g e their p r o p e r t i e s ( c o m - plex f o r m i n g ability, selectivity in t r a n s p o r t processes) if in- s t e a d of o x y g e n a t o m s " s o f t e r " n i t r o g e n a t o m s a r e a l s o in- c o r p o r a t e d i n t o the m a c r o r i n g8 - 1 0 1. Such c h i r a l d i a z a - c r o w n e t h e r s built u p f r o m s u g a r s w e r e p r e p a r e d first by
L a i d l e r a n d S t o d d a r t f r o m l , 2 : 5 , 6 - d i - 0 - i s o p r o p y l i d e n e - D - m a n n i t e1 1 1 a n d later by Polish a n d H u n g a r i a n r e s e a r c h
M eg H H o A P R
o d r *
c,HI 5
1 : R = H 2 : R = CHjCOOH 3 : R = CH.COCt
CI
HjN^
o.
)
toluene CHCUCt
o o o o Et,N
/""V
C°
HN NH
% o->
\_y
Et,N
10
Me0H (An-^, X
ÂL0,3 » ,0 rVfb,o , V
°Y°H Y ^ C«H5 X
5: X = 0 6: X = Hj
X
" t . r - ' l , r x h ? "
C6h5 x
8 : x = 0 9 : X =• H2
Meg H r ^ N ^
r S j o oV V H
c6H5
11 X = 0 9 X = H2
w o r k e r s f r o m m e t h y l 4 , 6 - O - b e n z y l i d e n e - a - D - m a n n o - , -gal- acto-, a n d - g l u c o p y r a n o s i d e1 2 - 1 6 1.
Bicyclic c r y p t a n d m o l e c u l e s h a v e p a r t i c u l a r c o m p l e x - f o r m i n g a n d selectivity porperties1 7 1 8 1. If t h e s e m o l e c u l e s a r e chiral, e.g. t h e i r s y n t h e s i s s t a r t s f r o m m o n o s e s , t h e n t h e y c a n also be used in t h e field of c h i r a l r e c o g n i t i o n .
P i e t r a s z k i e w i c z et al. h a v e s y n t h e s i z e d a c h i r a l c r y p t a n d of t y p e [2.2.1] f r o m a m o n o s a c c h a r i d e1 2 - 1 5 1. T h e d i s a d v a n - t a g e of the m e t h o d is t h a t o n e of t h e r e a c t i o n s t e p s c a n be realized o n l y at h i g h p r e s s u r e (8000 bar), a n d o n l y s m a l l q u a n t i t i e s of s u b s t a n c e a r e f o r m e d b e c a u s e of the d i m e n s i o n s of t h e a p p a r a t u s . T h e p r o p e r t i e s of t h e p r e p a r e d c o m p o u n d s h a v e n o t b e e n r e p o r t e d .
W e h a v e s y n t h e s i z e d c r o w n a m i n e s a n d [2.2.2] c r y p t a n d s u s i n g glucose a s o n e of t h e s t a r t i n g c o m p o u n d s1 6 1. In this P a p e r we discuss b o t h t h e e x p e r i m e n t a l details a n d t h e d a t a o n c o m p l e x - s t a b i l i t y m e a s u r e m e n t s . T h e s y n t h e s i s of t h e s e c o m p o u n d s w a s c a r r i e d o u t a c c o r d i n g t o t h e h i g h - d i l u t i o n t e c h n i q u e ( d e v e l o p e d by L e h n et al.)17'. M e t h y l 4 , 6 - O - b e n - zylidene-ot-D-glucopyranoside (1) w a s t r e a t e d in tert-butyl a l c o h o l w i t h m o n o c h l o r o a c e t i c acid in t h e p r e s e n c e of p o - t a s s i u m t e r t - b u t o x i d e t o give the d i a c i d d e r i v a t i v e 2 w i t h 3 6 % yield. W e tried t o p e r f o r m t h e a l k y l a t i o n of t h e h y d r o x y g r o u p s in 1 a l s o w i t h e t h y l b r o m o a c e t a t e by u s i n g solid K O H a n d p h a s e - t r a n s f e r c a t a l y s t s , b u t o b t a i n e d o n l y p o o r yields.
C o m p o u n d 2 w a s c o n v e r t e d in c h l o r o f o r m w i t h oxalyl d i c h l o r i d e i n t o t h e r e s p e c t i v e bisacid c h l o r i d e 3. T h e r e a c - tion of 3 with l , 8 - d i a m i n o - 3 , 6 - d i o x a o c t a n e1 9 , 2 0 1 (4) w a s c a r - ried o u t in a 5 : 1 t o l u e n e / c h l o r o f o r m m i x t u r e by u s i n g the h i g h - d i l u t i o n t e c h n i q u e . A f t e r p u r i f i c a t i o n by c o l u m n c h r o - m a t o g r a p h y t h e m o n o c y c l i c b i s a m i d e 5 w a s o b t a i n e d in 2 8 % yield. 5 w a s r e d u c e d in T H F w i t h L i A l H4 t o give the c h i r a l d i a z a - c r o w n 6 ( 9 2 % ) .
F o r the p r e p a r a t i o n of c r y p t a n d 9 t w o r o u t e s w e r e de- veloped. T h e first m e t h o d essentially involves a c y l a t i o n of c o m p o u n d 6 w i t h t h e b i f u n c t i o n a l l , 6 - d i c h l o r o c a r b o n y l - 2 , 5 - d i o x a h e x a n e1 7 1 (7) f o r m i n g a b r i d g e b e t w e e n t h e t w o n i t r o - gen a t o m s . T h i s r e a c t i o n w a s c a r r i e d o u t in 1:1 t o l u e n e / c h l o r o f o r m m i x t u r e in the p r e s e n c e of t r i e t h y l a m i n e a c c o r d - Liebigs Ann. Chem. 1990, 1161-1164 © V C H Verlagsgesellschaft mbH, D-6940 Weinheim, 1990 0170 - 2041/90/1212-1161 $ 3.50 + .25/0
1162 P. Bakó, L. Fenichel, L. Tőke ing t o the h i g h - d i l u t i o n t e c h n i q u e . After c h r o m a t o g r a p h i c
p u r i f i c a t i o n , the bicyclic b i s a m i d e derivative 8 was o b t a i n e d in a yield of as low as 1 0 % , p r o b a b l y d u e t o steric h i n d e r - a n c e of the reaction centers in 6.
A n o t h e r synthetic p a t h w a y gave better results. T h u s , t h e r e a c t i o n of the u n s u b s t i t u t e d d i a z a - c r o w n ether 10171 with the chiral diacid d i c h l o r i d e 3 in t h e w a y described a b o v e g a v e t h e bicyclic b i s a m i d e 11 in 2 1 % yield, f r o m which the chiral c r y p t a n d of type [2.2.2] (9) w a s o b t a i n e d by r e d u c t i o n with LiAlH4. Interesting t o n o t e t h a t the r e d u c t i o n of bis- a m i d e of type [2.2.1] with L i A l H4 c a n be realized only in a very p o o r yield, o r it d o e s n o t p r o c e e d at all a c c o r d i n g to ref.'5 ) b u t we succeeded in r e d u c i n g the b i s a m i d e 11 of type [2.2.2] similarly with L i A l H4 (87%).
A bicyclic c r y p t a n d built u p f r o m two m o l e s of glucose w a s o b t a i n e d by the r e a c t i o n of the d i a z a - c r o w n ether 6 with t h e chiral diacid dichloride 3. T h e bicyclic bisamide 12 w a s o b t a i n e d in 9 % yield. In this reaction t w o d i a s t e r e o m e r s m a y be f o r m e d . After purification, T L C of c o m p o u n d 12 revealed t w o spots. T h e s e t w o c o m p o n e n t s c o u l d neither be s e p a r a t e d n o r identified spectroscopically. T h e r e d u c t i o n of the i s o m e r i c m i x t u r e by L i A l H4 yielded t h e stereoisomeric [2.2.2] c r y p t a n d s 13a a n d 13b in a c o n s i d e r a b l e yield.
r R C6H5
J
An < n) lH | OMe 0Me = h ' N<0 H r H im 4 i t fir
0^0 - Y ^ hTH) ( J J ^ y ^ L
^ R C6Hs CtH5 R
a. b
12 : R - 0 13: R - H2
Complex-Forming Characteristics
T h e a s s o c i a t i o n c o n s t a n t s f o r the c o m p o u n d s 5, 6, 9, 13 a n d 10 (the latter for c o m p a r i s o n ) were m e a s u r e d by C r a m ' s m e t h o d2" using lithium, s o d i u m , p o t a s s i u m a n d a m m o n i u m picrates as c a t i o n sources. T h e log values a r e listed in T a b l e 1.
Tab. 1. Association constants (log Aa) of diaza-crown compounds and cryptands in chloroform at 22 °C
Host Li + log K,
Na + K+ NH J
5 3.87 4.60 4.25 4.11
6 6.39 6.31 5.82 6.65
10 6.85 6.45 6.59 8.81
9 6.26 8.88 9.37 9.57
13 5.57 6.34 6.26 6.35
T h e c o m p l e x stability c o n s t a n t s of s u g a r c r o w n a m i n e 6 for these ions are by 1.5 to 2.5 o r d e r of m a g n i t u d e higher t h a n t h o s e of b i s a m i d e 5 a n d t h e o r d e r of selectivity is also
different. In the c a s e of 5 t h e t e n d e n c y t o c o o r d i n a t i o n of n i t r o g e n i n c o r p o r a t e d i n t o the c a r b o x a m i d e f u n c t i o n d e - creases.
It c a n be seen f r o m a c o m p a r i s o n of the u n s u b s t i t e d c r o w n a m i n e 10 a n d c o m p o u n d 6 t h a t the p r e s e n c e of t h e s u g a r unit d i m i n i s h e s the t e n d e n c y t o c o m p l e x f o r m a t i o n , espe- cially in t h e case of t h e a m m o n i u m c a t i o n , a n d the selectivity is also d e c r e a s e d . T h i s p h e n o m e n o n m a y be a t t r i b u t e d t o the fact t h a t t h e ring is flexible in m o l e c u l e 10 while in t h e case of 6 the g l u c o p y r a n o s i d e unit m a k e s the c r o w n ring rigid a n d t h u s h i n d e r s c o m p l e x f o r m a t i o n . T h e steric hin- d r a n c e m a y a l s o c o n t r i b u t e t o t h e decrease of the stability which is m o s t p r o n o u n c e d with the large a m m o n i u m c a t i o n . It is r e m a r k a b l e t h a t t h e stability c o n s t a n t s for c r y p t a n d 9 are by 2.5 t o 3.5 o r d e r of m a g n i t u d e higher with the s o d i u m c a t i o n s b u t p a r t i c u l a r l y w i t h t h e p o t a s s i u m a n d a m m o n i u m c a t i o n , t h a n the c o r r e s p o n d i n g values for 6. T h e c r y p t a n d , 13 built u p f r o m t w o g l u c o s e moieties, f o r m s a w e a k e r c o m - plex with e a c h c a t i o n t h a n c o m p o u n d 9 does. P r o b a b l y , t h e t w o s u g a r moieties r e d u c e t h e flexibility of t h e c r y p t a n d , a n d at the s a m e t i m e t h e effect of their steric h i n d r a n c e increases.
T h e s a m e applies t o t h e d e c r e a s e in selectivity.
D a t a o n the chiral r e c o g n i t i o n ability of t h e c o m p o u n d s described in this p a p e r will be r e p o r t e d later.
We thank Dr. József Tamás for recording some of the mass spec- tra.
E x p e r i m e n t a l
' H - N M R spectra: Perkin-Elmer R12 and Jeol FX-100(in CDCfi;
T M S as internal standard). — UV spectra: Hitachi-Perkin-Elmer 124. — Mass spectra: Jeol J M S - O L SG-2. — Elemental analysis:
Perkin-Elmer 240 automatic analyser. — TLC: Kieselgel 60 F254 or A1203 150 F254 Type T (Merck), eluent toluene/methanol mixtures (10:1 — 10:5); detection with DragendorfTs reagent22'. — Column chromatography: Kieselgel 60 (0.2—0.063 mm) (Merck).
Methyl 4,6-0-Benzylidene-2,3-di-0-carboxymethyl-a-D-glucopyr- anoside (2): 14.0 g (0.36 mol) of metallic potassium was added to 300 ml of dry tBuOH under N2 and stirred at 60 °C until the re- action was completed (H2 evolution stopped). After cooling, a so- lution of 20.0 g (0.07 mol) of 1 in 150 ml of dry tBuOH was added to the mixture which was heated at reflux with stirring for 1 h. A solution of 13.5 g (0.14 mol) of chloroacetic acid in 50 ml of dry tBuOH was then added, and the mixture was stirred at boiling temp, for 24 h. After cooling it was poured into ice/water, tBuOH was distilled off in vacuo, the aqueous residue was extracted three times with 40 ml of CHCfi, and the combined extracts were acidified with HC1 to pH = 1. The precipitate formed was filtered, dissolved in CHCfi, repeatedly washed with water, dried with Na2S04, and evaporated to dryness in vacuo to obtain 22 g of raw product, which gave 10.3 g (36%) of 2 after recrystallization from a mixture of 25 ml of acetone and 25 ml of benzene; m.p. 135—136°C, [oc]2d2 = 4-88.1 (c = 1.1, in CHC13). - 'H NMR: 5 = 3.36 (s, 3H, OCHj), 3 . 2 - 4 . 0 (m, 9H), 4.33 (s, 4H, OCH2CO), 4.85 (d, J = 3.5 Hz, 1H, anomeric H), 5.40 (s, 1 H, benzylidene H), 7.10-7.48 (m, 5H, aromatic H), 9.23 (broad, 2H, COOH).
C,8H220,O (398.4) Calcd. C 54.27 H 5.52 Found C 54.41 H 5.44
Methyl 4,6-0-Benzylidene-2,3-di-0-chlorocarbonylmethyl-a-D- glucoyranoside (3): 10.0 g (25 mmol) of 2 was dissolved in 80 ml of
Liebigs Ann. Chem. 1990, 1 1 6 1 - 1 1 6 4
Novel Diaza-Crown Ether and Cryptands from Glucopyranose 1163 dry CHClj and added to a solution of 15 m (176 mmol) of oxalyl
dichloride in 80 ml of dry CHClj (containing 3 drops of pyridine).
The mixture was kept at room temp, for 40 h, then concentrated in vacuo. The remaining syrup was treated with anhydrous petro- leum ether for a few hours to yield a white amorphous precipitate of 6.1 g (56%) of 3; m.p. 141 - 1 5 0 ° C (dec.), [<x]2D2 = +34.0 (c = 1.1 in CHClj). - 'H NMR: 8 = 3.44 (s, 3H, OCH3), 3.3-4.4 (m, 9H, CH and CH2 groups), 4.60 and 4.72 (s, 2H, OCH2CO), 4.95 (d, J = 4 Hz, 1H, anomeric H), 5.43 (s, 1H, benzylidene H), 7.30-7.66 (m, 5 H, aromatic H).
CI8H20C12O8 (435.3) Calcd. C 49.66 H 4.63 CI 16.31 Found C 49.38 H 4.68 CI 16.24 Glucopyrano-Fused Derivative 5 of l,4,10,13-Tetraoxa-7,16-di- azacyclooctadecane-8,15-dione: A solution of 3.3 g(7.5 mmol) of 3 in a mixture of 30 ml of dry CHCI3 and 70 ml of dry toluene and a solution of 2.2 g (15.0 mmol) of 4 in 100 ml of dry toluene were added simultaneously under argon and with vigorous stirring to 200 ml of dry toluene during a period of 7—8 h. The mixture was left standing for about 12 h and then filtered. The filtrate was evap- orated to dryness in vacuo to yield 4.9 g of a raw product which was purified by column chromatography (450 x 35 mm, Kieselgel 60,100 g, eluent CHClj/MeOH, 10:1); yield 1.1 g (28%) of colorless 5, m.p. 108 —110°C (ethanol/heptane), [a]?,2 = +87.4 (c = 1 in CHCI3). - 'H N M R : 8 = 3.41 (s, 3H,OCHj),3.43-3.90(m, 18H), 4.12-4.40 (m, 4H, OCH2CON), 4.87 (d, J = 4 Hz, 1H, anomeric H), 5.52 (s, 1H, benzylidene H), 7.31-7.48 (m, 5H, aromatic H). - MS (70 eV): m/z (%) = 510 (49.4) [ M+] , 174 (25), 149 (40), 144 (22.5), 118 (32.5), 105 (66), 102 (82), 91 (82), 77 (46.6).
C24H34N2O,0 (510.5) Calcd. C 56.46 H 6.71 Found C 56.31 H 6.62 Glucopyrano-Fused Derivative 6 of l,4,10,13-Tetraoxa-7,16-di- azacyclooctadecane: A solution of 2.0 g (3.92 mmol) of 5 in 20 ml of dry T H F was added dropwise to a stirred suspension of 1.6 g (42.0 mmol) of LiAlH4 in 50 ml of dry T H F under argon. The mixture was stirred and heated at reflux for 2 h. After cooling, excess LiAlH4
was decomposed with 15 ml of ethyl acetate and 10 ml of water.
The precipitate was separated, washed with THF, and the combined filtrates were concentrated in vacuo; yield 1.73 g (92%) of 6 as a yellow syrup, [a]2D2 = +56.9 (c = 1, CHClj). - 'H NMR: 8 = 2.15 - 3.10 (m, 10 H, NCH2), 3.40 (s, 3 H, OCH3), 3.37-4.36 (m, 18 H, CH2 and CH groups), 4.82 (d, J = 4.5 Hz, 1H, anomeric H), 5.49 (s, 1H, benzylidene H), 7.22-7.45 (m, 5H, aromatic H).
C24H38N208 (482.6) Calcd. C 59.73 H 7.93 Found C 59.28 H 7.69
Glucopyrano-Fused Derivative 8 of 4,7,13,16,21,24-Hexaoxa-l.lO- diazabicyclof8.8.8]hexacosane-2,9-dione: A solution of 4.2 g (8.7 mmol) of 6 in a mixture of 100 ml of dry toluene and 50 ml of dry CHC13 and a solution of 1.9 g (8.8 mmol) of 7 in 150 ml of dry toluene were added simultaneously dropwise to vigorously stirred dry toluene 300 ml [containing 2.3 g (22.7 mmol) of Et3N] at room temp, during a period of 8 h. The reaction mixture was left standing for about 12 h, Altered, the filtrate was evaporated to dryness in vacuo, and the residue was eluated through a column (400 x 25 mm, 70 g A1203, activity II, neutral) with a mixture of benzene/
petroleum ether (2:1); yield 0.5 g(10%), m.p. 101 -102°C(benzene/
petroleum ether), [a]?,2 = +64.2 (c = 1 in CHClj). - 'H NMR:
8 = 3.38 (s, 3H, OCHj), 3.44-3.92 (m, 30H, CH and CH2 groups), 4.2-4.32 (m, 4H, CH2CON), 4.68 (d, J = 4 Hz, 1H, anomeric H), 5.44 (s, 1H, benzylidene H), 120-1.SI(m, 5H, aromatic H). - MS (75 eV): m/z (%) = 624 (100) [ M+] ,
CJOH„N20,2 (624.7) Calcd. C 57.68 H 7.09 N 4.48 Found C 57.61 H 7.13 N 4.42
l,4,10,13-Tetraoxa-7,16-diazacyclooctadecane (10): This was pre- pared according to the method of Lehn71, with the exception that toluene was used as solvent instead of benzene for the high-dilution technique. The average yield of several reactions was 58% (ref.171 56%); m.p. 112-114°C (ref.17' 115— 116"C). The 'H-NMR data agree with those published in the literaturel7>.
Glucopyrano-Fused Derivative 11 of 4,7,13,16,21,24-Hexaoxa- 1,10-diazabicyclof8.8.8Jhexacosane-11,18-dione: A solution of 4.6 g (17.5 mmol) of 10 in 300 ml of dry toluene and a solution of 7.6 g (17.6 mmol) of 3 in a mixture of 200 ml of dry CHClj and 100 ml of dry toluene were added simultaneously dropwise to vigorously stirred dry toluene [600 ml, containing 4.5 g (44.4 mmol) of EtjN]
at room temp, over a period of 8 h. The reaction mixture was left standing for about 12 h, Altered, the Altrate was concentrated in vacuo, and the residue was puriAed by column chromatography (400 X 25 mm, 100 g of A12OJ, activity II, neutral) with a mixture of benzene/petolcum ether (2:1); yield 2.3 g (21%), m.p. 9 4 - 9 5 ° C (benzene/petroleum ether), [ a ] " = +64.4, (c = 1 in CHClj). — 'H NMR: 8 = 3.37 (s, 3H, OCHj), 3.44-3.92 (m, 30H, CH and CH2 groups), 4.2-4.36 (m, 4H, CH2CON), 4.66 (d, J = 4 Hz, 1 H, anomeric H), 5.42 (s, 1H, benzylidene H), 7.21-7.5 (m, 5H, aro- matic H). - MS (75 eV): m/z (%) = 624 (100) [ M+] , 537 (20), 149 (37), 128 (41), 105 (31), 100 (33), 91 (36), 56 (75), 45 (47).
C j o H ^ O . J (624.7) Calcd. C 57.68 H 7.09 N 4.48 Found C 57.53 H 7.10 N 4.41 Glucopyrano-Fused Derivative 9 of 4,7,13,16,21,24-Hexaoxa-1,10- diazabicyclof 8.8.8Jhexacosane: The reduction of 11 with LiAlH4
was carried out as described for 6; yield 84%. 9 is of greasy con- sistence; [a]?? = +12.3, (c = 1 in CHClj). - 'H NMR: 8 = 2.75 (m, 12H, NCHJ, 3.35 (s, 3H, OCHj), 3.30 - 4 . 0 2 (m, 18H, CH and CH2 groups), 4.54 (s, 8H, 0CH2CH20), 4.77 (d, J = 4 Hz, 1H, anomeric H), 5.49 (s, 1H, benzylidene H), 7.17 — 7.46 (m, 5H, aro- matic H). - MS (75 eV): m/z (%) = 569 (49) [ M+] , 521 (23), 319 (19), 315 (45), 301 (42), 158 (20), 144 (51), 128 (24), 114 (100), 100 (54), 91 (22).
CjoH48N2OIO (596.7) Calcd. C 60.38 H 8.10 N 4.69 Found C 59.92 H 7.98 N 4.55 Bis(glucopyrano)-Fused Derivative 12 of 4,7,13,16,21,24-Hexa- oxa-l,10-diazabicycio[8.8.8]hexacosane-2,9-dione: The reaction of 6.2 g (12.8 mmol) of 6 with 6.2 g (14.2 mmol) of 3 was carried out as described for 8. After column chromatography, 1.0 g (9%) of 12 was obtained; m.p. 125-128°C (CHClj/petroleum ether), [oc]£ = +48.9 (c = 1 in CHClj). - 'H NMR: 8 = 3.40 (s, 6H, OCHj), 3.48-3.95 (m, 32H, CH and CH2 groups), 4.12-4.5 (m, 4H, CH2CON), 4.68 (d, J = 4 Hz, 2H, anomeric H), 5.48 (s, 2H, ben- zylidene H), 7.2-7.55 (m, 10 H, aromatic H). - MS: m/z = 867 [M + N a ]+ (FAB-ionization technique).
CoHHNJO* (844.9) Calcd. C 59.71 H 6.68 N 3.31 Found C 59.49 H 6.58 N 3.25 Bis(glucopyrano/-Fused Derivative 13 of 4.7,13,16,21,24-Hexa- oxa-l,10-diazabicyclof8.8.8/hexacosane: The reduction of 12 with LiAlH4 was performed as described for 6; yield 83%, yellow sub- stance of greasy consistence, [ a ] " = +27.4 (c = 1 in CHClj). — 'H NMR: 8 = 2.75 (m, 12H, NCH2), 3.38 (s, 6H, OCHj), 3.23-4.3 (m, CH and CH2), 4.68 (d, J = 4 Hz, 2H, anomeric H), 5.48 (s, 2H, benzylidene H), 7.2-7.4 (m, 10 H, aromeric H).
C42H60N:O,4 (816.9) Calcd. C 61.75 H 7.40 N 3.42 Found C 61.52 H 7.21 N 3.36 Liebigs Ann. Chcm. 1990, 1161-1164
1164 P. Bakó, L. Fenichel, L. Tőke
CAS Registry Numbers
1: 57701-27-6 / 2 : 92713-97-8 / 3 : 92713-98-9 / 4: 929-59-9 / 5:
92713-99-0 / 6: 92762-33-9 / 7 : 31255-09-1 / 8: 129570-32-7 / 9:
129592-59-2 / 10: 23978-55-4 / 11: 129570-33-8 / 12a: 129592- 60-5 / 12b: 129592-61-6 / 13a: 129570-34-9 / 13b: 129570-35-0 / lithium picrate: 18390-55-1 / sodium picrate: 3324-58-1 / potassium picrate: 573-83-1 / ammonium picrate: 131-74-8 / glucose: 50-99-7
11 J. F. Stoddart Synthetic Chiral Receptor Molecules from Natural Products in Progress in Macrocyclic Chemistry (Izatt, Christen- sen, Ed.), vol. 2, p. 1 7 4 - 2 4 5 , Wiley, New York 1981.
2) J. F. Stoddart, Chiral Crown Ethers, Topics in Stereochemistry (Eliel, Wilen, Eds.), vol. 17, p. 2 0 7 - 2 7 9 , Wiley, New York 1987.
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41 P. Bakó, L. Fenichel, L. Tőke, M. Czugler, Liebigs Ann. Chem.
1981,1163.
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71 G. Tóth, W. Dietrich, P. Bakó, L. Fenichel, L. Tőke, Carbohydr.
Res. 168 (1987) 141.
" J . M. Lehn, P. Vierling, Tetrahedron Lett. 21 (1980) 1323.
9> K. Matsushima,. H. Kobayashi, Y. Nakatsuji, M. Okahara,
Chem. Lett. 1983, 701.
,0) H. Tsukube, Bull. Chem. Soc. Jpn. 57 (1984) 2685.
1,1 D. A. Laidler, J. F. Stoddart, J. Chem. Soc., Chem. Commun.
1976, 979.
121 M. Pietraszkiewicz, J. Jurczak, J. Chem. Soc., Chem. Commun.
1983, 132.
131 M. Pietraszkiewicz, J. Salanski, J. Jurczak, J. Chem. Soc., Chem.
Commun. 1983, 1184.
141 M. Pietraszkiewicz, J. Jurczak. Tetrahedron 40 (1984) 2967.
151 M. Pietraszkiewicz, P. Salanski, J. Jurczak, Tetrahedron 40 (1984) 2971.
161 P. Bakô, L. Fenichel, L. Töke, Acta. Chim. Hung. 116 (1984) 323.
17) B. Dietrich, J. M. Lehn, J. P. Sauvage, J. Blanzat, Tetrahedron 29 (1973) 1629.
18) B. Dietrich, J. M. Lehn, J. P. Sauvage, Tetrahedron 29 (1973) 1647.
191 D. Landini, F. Montanari, F. Rolla, Synthesis 1978, 223.
101 O. A. Gansow, A. R. Kausar, K. B. Triple«, J. Heterocycl. Chem.
18 (1981)297.
2,) S. S. Moore, T. L. Tarnowski, M. Newcomb, D. J. Cram, J. Am.
Chem. Soc. 99 (1977) 6398.
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[74/90]
Liebigs Ann. Chem. 1990,1161-1164
B3
Journal of Inclusion Phenomena and Molecular Recognition in Chemistry 16: 17-23, 1993. 1 7
© 1993 Kluwer Academic Publishers. Printed in the Netherlands.
The Complexing Ability of Crown Ethers Incorporating Glucose
PETER BAKÓ, LÁSZLÓ FENICHEL and LÁSZLÓ TŐKE*
Department of Organic Chemical Technology, Technical University of Budapest, H-111J Budapest, Műegyetem rkp. 3, Hungary.
(Received: 30 December 1992; in final form: 17 May 1993)
Abstract The complexing (in CHCb) and extracting abilities of 18-crown-6 type compounds (1-15) were measured with Li, Na, K and NH4 cations. The substituents on the sugar part affected these properties significantly (Ka = 103—107). Some substituents, like acetyloxy groups (3) decreased whereas others, like tosyloxy groups (10,11) significantly increased the complexing ability and thus changed the selectivity. The compound with four tosyloxy groups (11) shows an excellent picrate salt extracting ability in a CHaCh-water system.
Key words: Crown ether, complex formation, extraction ability.
1. Introduction
A variety of monosaccharides has been used as starting material for the synthesis of several types of chiral crown ethers [1,2], and the stabilities of their complexes with' metal and ammonium cations have been determined, mainly in a binary CDCl3-water system [1,3,4].
In the case of metal, ammonium, methylammonium and t-butyl ammonium picrates, the values of the association constants (Ka) were determined by UV spectrophotometry, following the extraction of the aqueous solution of the picrate salt of the crown ether with deutero chloroform [1, 4]. The complexing ability of sugar crowns toward ammonium ions was measured with t-butyl ammonium thiocyanate by *H NMR spectroscopy [5,6].
2. Experimental
The synthesis of the sugar-based crown ethers 1-15 has been described by us previ- ously [7-10]; the dibenzo-18-crown-6 used for comparison is a Merck product. The complexing constants of the compounds with Li, Na, K and ammonium picrates were measured in chloroform, by UV spectrometry, using the method of Cram [4], Most of the crown ethers were insoluble in water: solubilities were 0.5% of the total used. The distribution constants of the water-soluble crown ethers between water and chloroform were determined in independent experiments and these constants
* Author for correspondence.
1 8 PÉTER B A K Ó ET AL.
l 2 - 1 5 16
Fig. 1.
were taken into consideration in the calculations of Ka values [14, 15]. Although the host-guest stoichiometric ratio in the solution was unknown, for the similar 18-crown-6 type sugar crowns the literature describes 1 : 1 complexes only [1], and our calculations were based on this stoichiometry.
The complex forming ability of some glucopyranoside compounds having ben- zylidene, benzyloxy, acetoxy, and tosyloxy substituents was measured with metal picrates under the same conditions as in the case of the crown ethers. It has been found that these groups are not able to form complexes with alkali metal and ammonium picrates.
The alkali metal and ammonium picrates were prepared and purified by the method of Wong [11]. »
Extraction ability was measured by the method of Kimura et al. [12] with the above mentioned picrates in a CK^CE-water system, by means of UV spectrometry (using a Hitachi Perkin-Elmer 124 spectrometer).
3. Results and Discussion
3 . 1 . COMPLEXING ABILITY
In all the compounds investigated (1-15), the ring is always of the 18-crown-6 type, and the substituents on the sugar part vary (R{ denotes the substituents on the two primary carbons, R2 those on the two secondary carbons: Figure 1). Consequently, in this case one can study the effect of substituents on complexing ability (or salt extracting ability), i.e. the so-called lateral discrimination. The lateral groups may have a secondary interaction with the guest molecules. This interaction is a result of several factors: they may be steric effects or hydrophilic and hydrophobic effects (the crown ether also encounters water molecules during the measurement). These effects occur in a complex way, strengthening or weakening one another, and thus it is hard to predict scientifically the values of the resulting complexing constants.
We examined C.P.K. space-filling molecular models of the crown ethers substi- tuted by different groups. The substituents were changed only on the 4C and 6C
CROWN ETHERS INCORPORATING GLUCOSE 1 9
TABLE I. Association constants of crown Compounds (1-15) (log Ka in Chloroform at 22°C.a
Crown log Ka
R2
Li+
compd. Li+ Na+ K+ NH+
1 CK *CH — C6H5 4.14 4.05 5.04 4.12
<K
2 OH OH 4.04 4.50 4.85 4.01
3 OAc OAc 3.57 3.20 4.46 3.58
4 Br OBz 3.68 4.38 4.16 3.96
5 H OH 4.75 5.05 4.78 4.56
6 Br OH 3.57 3.95 4.40 3.53
7 OH OBn 3.58 4.76 4.70 4.38
8 OTr OAc 4.15 4.80 4.47 3.67
9 OH OAc 3.75 3.62 4.37 3.59
10 OTs OH 5.70 5.40 5.45 5.64
11 OTs OTs 6.17 6.23 6.00 5.81
12 OMs OH 4.47 4.16 4.65 4.33
13 OMe OMe 3.18 4.21 4.35 3.91
14 OBu OBu 4.25 4.33 4.38 3.82
15 OBn OBn 3.56 4.01 4.09 3.72
16 dibenzo-18-crown-6 4.08 4.44 7.85 5.96
Ac = acetyl, Bz = benzoyl, Tr = trityl, Ts = tosyl, Ms = mesyl, Me = methyl, Bu = butyl, Bn = benzyl
a Aqueous phase (0.5 mL); [picrate] = 0.15 M; organic phase (CHCI3,0.2 mL); [crown ether] = 0.075 M; Réf. [4],
atoms of the pyranose residues (1-15). We found that these substituents did not induce conformational changes on the sugar ring and on the crown ring.
As a comparison, the properties of dibenzo-18-crown-6 (16) were also mea- sured. As can be seen from Table I, the substituents found on the sugar parts affect the complexing ability significantly: the association constants, Ka, are in the 103-
107 range. The weakest complexing ability is shown by the substances bearing two or four acetyloxy groups (3, 9), bromine and benzoyloxy groups (4, 6), four methoxy groups (13) or four benzyloxy groups (15).
Tetrabutoxy (14) and hexamethoxy ethers (13) have nearly identical properties, except that the lithium complex of 14 is an order of magnitude stronger than that of 13.
20 PETER BAKÓ ET AL.
There are substituents which promote complex formation with all cations: the presence of two tosyloxy groups (10) increases this ability by 1-1.5 orders of magnitude; that of four tosyloxy groups (11) by two orders of magnitude with respect to the benzylidene derivative (1).
As is known, the size of the 18-ring corresponds (on the basis of ion radii) to a selectivity sequence of NH4" ~ K+ > Na+ > Li+. This tendency also holds for our compounds: the majority forms the strongest complex with K+. There are, however, substituents which change this characteristic sequence of the basic crown:
the bromobenzoyloxy derivative (4), the unsubstituted (5), the benzyloxy (7), the trityloxy-acetyloxy (8) and the tetratosyloxy (11) derivatives all form the most stable complex with sodium. A comparison of the behaviour of 4 and 6 suggests that the crown ether becomes sodium selective on addition of benzoyloxy groups.
A comparison of 8 and 9 indicates that the trityloxy groups increase the stability of the sodium complex by more than one order of magnitude.
Tosyloxy groups (10, 11) not only enhance the complexing ability but also change the selectivity sequence, preferring primarily lithium and sodium, respec- tively.
In the case of the tetrasubstituted derivatives (il1 = R2), the stability of the complex with respect to K+ decreases in the sequence of OTs > OCHPh > OH >
OAc > OBu > OMe > OBn (Figure 2). Compared to the values measured with Na+, some selectivity is shown by 1 and 3 (OCHPh and OAc), inasmuch as there is a 1-1.2 order of magnitude difference between the Ka values obtained with Na+ and K+ ions.
The stability of the disubstituted compounds (R2 = OH) with respect to K+ decreases in the sequence of OTs > OH > H > OMs > Br (Figure 3), and compared to the Na+ values none of the compounds shows significant selectivity.
As can be seen, tosyloxy groups increase the stability of complexes with all cations, but suppress the differences thereby decreasing the selectivity.
We investigated the lipophilicity of compounds 1-15 by reverse- phase TLC on a silica gel plate modified by octadecyltrimethylsilane, with an ethanol-water (7 : 3) eluent. In this system the Rj values are characteristic of the lipophilicity of the crown ethers. We did not find any general connection between the lipophilicity and association constants (e.g. the order of lipophilicity is 1 > 10 > 3 but that of the Ka values is 10 > 1 > 3).
3 . 2 . EXTRACTION ABILITY
Table II shows the extraction ability of picrate salts of compounds 1, 2, 3, 4, 7, 10, 11 and 16 in the CH2Cl2-water system. The tendencies are similar to those of complex formation; substituents affect the extraction ability to a great extent depending on the type of ions. Dibenzo-18-crown-6 (16) used as reference shows a notable selectivity with potassium ions.
