Host Guest Complex Chemistry Macrocycles Synthesis, Structures, Applications Editors: F. V6gtle, E. Weber With 174 Figures and 46 Tables Springer-Verlag Berlin Heidelberg New York Tokyo 1985 Professor Dr. Fritz Vogtle Dr. Edwin Weber Institut fUr Organische Chemie und Biochemie Universitiit Bonn Gerhard-Domagk-StraBe 1 5300 Bonn 1 ISBN -13: 978-3-540-13950-8 e-ISBN -13: 978-3-642-70108-5 DOl: 10.1007/978-3-642-70108-5 Library of Congress Cataloging in Pnblication Data. Main entry under title: Host guest complex chemistry/macrocycles. Bibliography: p. Includes index. 1. Electron don~r-acceptor complexes--Adresses, essays, lectures. I. VogUe, F. (Fritz), 1939 - ll. Weber, E. QD474.H67 1985 541.2'8 84-23569 This work is subject to copyright. All rights are reserved, whether the whole orpart of the material is concerned, specifically those of translation, reprinting, re-use of illustrations, broadcasting, repro duction by photocopying machine or similar means, and storage in data banks. Under§54 of the Ger man Copyright Law where copies are made for other than private use, a fee is payable to "Verwer tungsgesellschaft Wort", Munich. © by Springer-Verlag, Berlin, Heidelberg 1985 The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. 2152/3020-543210 Table of Contens Crown-Type Compounds - An Introductory Overview E. Weber and F. Vogtle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Structural Chemistry of Natural and Synthetic Ionophores and their Complexes with Cations R. Hilgenberger and W. Saenger ............................ 43 Concept, Structure, and Binding in Complexation D. J. Cram and K N. Trueblood. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 125 Analytical Applications of Crown Compounds and Cryptands E. Blasius and K-P. Janzen ................................. 189 Crown Compounds as Alkali and Alkaline Earth Metal Ion Selective Chromogenic Reagents M. Takagi and K Ueno ..................................... 217 Photocontrol of Ion Extraction and Ion Transport by Photofunctional Crown Ethers S. Shinkai and O. Manabe .................................. 245 Bioorganic Modelling-Stereoseletive Reactions with Chiral Neutral Ligand Complexes as Model Systems for Enzyme Catalysis R. M. Kellogg. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 283 Complexation of Uncharged Molecules and Anions by Crown-'JYpe Host Molecules F. Vogtle, H. Sieger and W. M. MUller ....................... 319 The Calixarenes C. D. Gutsche ............................................. 375 Crown-Type Compounds - An Introductory Overview Dr. Edwin Weber, Prof. Dr. Fritz Vogtle Institut fUr Organische Chemie und Biochemie der Universitat Bonn, Gerhard-Domagk-Stra13e 1, D-5300 Bonn 1, FRG Table of Contents 1 Introduction . 3 2 Classification of Oligo-/Multidentate Neutral Ligands and of their Complexes. . . . . . . . . . . . . . 3 3 Crown-Type Ligands. . . . . . . . . . . . 3 3.1 Historical Crown Ethers, Nomenclature . 3 3.2 Variation Possibilities with Coronands . 5 3.3 Cryptands. . . . . . . . . . . . . . 10 3.4 Podands (Open-Chain Crown Compounds and Cryptands, Octopus Molecules). . . 11 3.5 Podandocoronands ... 14 3.6 Macrocyclic Oligoketones 15 3.7 Spherands. 16 4 Ligand Synthesis 16 4.1 Coronands 16 4.2 Cryptands. 17 4.3 Podands .. 17 5 Properties of Crown Compounds. 18 5.1 Hydrophilicity/Lipophilicity Balance 18 5.2 Crown Ethers as Cation Receptors . 18 5.2.1 Optimal Spatial Fit Concept and Circular Recognition. 18 5.2.2 Structure of Crystalline Complexes . . . 18 5.2.3 Complex Stability in Solution. . . . . . . . 19 5.2.4 Selectivity of Crown Ether Complexation. . . 19 5.3 Coronates - The Concept of Donor-Site Variation. 21 5.4 Complexation of Cryptands, Cryptate Effect and Spherical Recognition 22 5.5 Podates. . . . . . . . . . . . . . . . . . . . . . . . . . .. 23 Edwin Weber and Fritz VogUe 5.6 Complexation Kinetics of Neutral Ligands. 25 5.7 Recognition and Complexation of Molecular Cations 25 5.8 Chiral Crown Compounds and Chiral Recognition . 26 5.9 Multisite Receptors, Cascade Complexation and Ion-Pair Complexes 28 5.10 Anion Receptors and Neutral Molecular Complexes . . . . . . . . 29 6 Consequences of the Properties of Crown Compounds . 30 6.1 Lipophilisation and Phase Transfer of Ions 30 6.2 Ion-Pairing and Ion-Aggregation Effects. 31 6.3 Modifications in Chemical Reactivity. 31 6.3.1 Anion Activation . . . . . . . . 31 6.3.2 Nucleophilicity/Basicity Balance. . 32 6.3.3 Ambidency and Regioselectivity Control . 32 6.3.4 Effects of Cation Capture ..., . . . . 33 6.4 Modification of Reaction Mechanisms and of their Stereochemistry. 34 7 Application Possibilities 35 8 Acknowledgement . 35 9 References . . . . 35 2 Crown-Type Compounds 1 Introduction The scientific and practical interest in coronands (crown ethers), cryptands, podands as complexing agents for cations as well as for anions and neutral low molecular species is undeniable 1,2). The chemistry of crown compounds is steadily increasing. About 250 original papers dealing with crown chemistry appeared only in 1980. New molecules· with crown ether properties are constantly synthesized and new applications discov,?red. Owing to lack of space, only a small number of the original publications is men tioned here. Thus, in the literature compilation only some, but relevant works are selected for each chapter. Whenever possible, reference is made to reviews or review-like articles alone by means of which origin,al works can be consulted. The reviews given under ref. are considered to be the most relevant. The formulae 1) presented in the figures should be understood as representative structures outlining a specific field. 2 Classification of Oligo-/Multidentate Neutral Ligands and of their Complexes Today, a distinction is made between the classical ring oligoethers (crown ethers) and monocyclic coronands, oligocyclic spherical cryptands and the acyclic podands with respect to topological aspects 3). This classification and the topology are illustrated in Fig. 1, each figure representing the minimum number of donor atoms and chain segments characteristic of each class of compounds. Multidentate mono cyclic ligands with any type of donor atoms are called coronands ("crown compounds"), while the term crown ether should be reserved for cyclic oligoethers exclusively containing oxygen as donor atom. Moreover, a subdivision of each of the three respectively four classes of ligands according to the number of arms or bridges is possible. Because of their ability to take up ions and to transfer them across a lipophilic medium, these types of ligands also are often called ionophores, comparable to the structurally related polyether antibiotics, the ionophoric behaviour of which had been discovered first 4). In order to differentiate the crown ether ligands from their metal ion complexes, the terms coronand and coronate were suggested for the uncomplexed and com plexed species, respectively 3). Analogously used are the terms cryptand/cryptate and podand/podate (cf. Sects. 3.3. and 3.4.). 3 Crown-Type Ligands 3.1 Historical Crown Ethers, Nomenclature The first synthetic ionophores described by Pedersen in 19675), were the cyclic hexaethers 1 and 2, which have been simply called [18]crown-6 and dibenzo[18] crown-62f), in contrast to their cumbersome and less illustrative IUPAC nomen clature (Fig. 2). 6) 3 Edwin Weber and Fritz Vogtle Podands (open -chain) Coronands (cyclic) Cryptands (spherical) C-0~ ~O~ o~ 0~ 0 o 0 B-l.--0,J:,B "---./ ~O;; {I) Podand {MonopodandJ III Coronond (Monocoronond) (2) Cryptond r+o~o (0,(0, ko,fn-8~0~ 0 0 B+ 01:0; "'8 A A "to 0 ~°'t!"-r°iJ ~Dr-B~in V { 2 )P odond (Dipodond) ( 2 )C oronond I Oicoronond) (3) Cryptond I Tricryplond) B~O-Tn) ( 'f-'-f' ) C+o~ ~ r+o 0 0 0 BrT-o-1.0B A (~A+D~ ( "foDof" ) 'ito0 ~/0 o )( 0 n Yn V O 0'--f /f'o~B "-r0~ {3 I Podond (Tripodond) { 3 I Coronond (Tricoronond ) { G IC ryptond (Tetrocryptand) Fig, I. Topology and classification of organic neutral ligands 3) (D = donor atom, A = anchoring group, n = chain segment without donor atom, B = bridgehead atom) "Dibenzo" stands for both of the benzene nuclei annexed to the ring while "[18]" in square brackets means the number of ring atoms. The class specification "crown" is followed by the number of heteroatoms in the ring; in this case "6", The above notation is now commonly accepted and generally serves to give a rough characterisation of medium- to many-membered cyclic polyethers in which the oxygen atoms are mostly connected via ethan a bridges and in which annexed benzene and cyclohexane rings may also be present (Fig, 2), 7) As Pedersen's crown notation is not unequivocally defined with regard to the location of the donor atoms, the benzene nuclei, the cyclohexane units or other ring components, even in simple cases, a more systematic and widely applicable nomenclature covering all kinds of cyclic and noncyclic ligands and also their complexes has been proposed recently (cf. Figs, I and 2) In principle, the same 3), symbolisms are retained but in addition it is specified as follows: The number preceding the angular brackets "( )" indicates the ring size. In the presence of aromatic and heteroaromatic units in the ring, the shortest way to the next donor atom is considered. The angular brackets contain in the order given: I) donor 4 0(0 10 :0 0 Structure: r I I :::,.. 0 0 ~ ~o-.J Nr. 2 IUPAC-designation 1,4,7, 10, 13, 16-hexaoxa 2,5,8,15,18,21-hexaoxa 2,5,8,15,18,21-hexa cyclooctadecane tricyclo[20.4.0.09•14] oxatricyclo hexacosa- [20.4.0.09,14] 1(22),8,11,13,23,24· hexacosane hexaene" Short name [18]crown-6 dibenzo[18]crown-6 dicyclohexano[18] (Pedersen's crown crown-6 nomenclature) Notation [18]C-6 DB[18]C-6 DCH[18)C-6 New nomenclature 18( 06coronand -6) 18(06(1,2)benzeno.22· 18(0 6(1 ,2)cyclo system (1,2)benzeno.22coro hexano .22.(1,2) nand-6) cyclohexano.2 cbro 2 nand-6) " Phane nomenclature: 1,4,7,14,17,20-hexaoxa[7.7] (l,2)benzenophane Fig. 2. Nomenclature of crown ethers heteroatoms expressed by elemental symbols; 2) bridges, i.e. C--C chains between the donor atoms, denoted by numbers which correspond to the bridging C-atoms, bridge units like aromatic nuclei or more complex groups (position marked in round brackets). The designation "2" for ethano, the most common bridge, is omitted if only this kind of bridge unit is present or if such a procedure does not curtail the clarity of the structure (cf. 18< 06-coronand-6»); 3) the class name (e.g. coronand), and 4) the total number of donor heteroatoms. In the case of mixed O/N/S macrocycles where ether oxygens are successively replaced by other heteroatoms (combinations s.b.), the sequence of donor sites in the ligand skeleton is given by heteroelemental symbols arranged in the order of priority laid down by the IUPAC rules. Heterocycles with donor sites (s.b.) are treated as single atoms. The sequence for the chain segments without donor atoms correspond to that of the heteroatoms, beginning with the donor atom of highest priority (cf. structures 2 and 3 in Fig. 2). Substituents and functional groups in the basic skeleton (class name) are denoted by prefixes and suffixes. The numbering is principally carried out according to the IUPAC rules (this is also valid for the cryptands but does not strictly apply to podands; s.b.). Altogether, the new proposal of nomenclature extended in Sections 3.3. and 3.4. allows an essentially easier recognition of the ligand type and other characteristics such as topology and donor centers. 3.2 Variation Possibilities with Coronands (Fig. 3-11) Since the discovery of crown ethers efforts have not diminished to synthesize 8) crown species with other distributions, numbers and types of donor heteroatoms like nitrogen or sulfur 1.2): 5 Edwin Weber and Fritz Vogtle (0") r?y0 0) ~O 0 ~OJ S9a.101 Fig. 3. Stiffening of the [l81crown-6 skeleton by benzo condensation r-\ 1\0 ) (0 0) \ 0 0 J Co ~oJ 0 l.....-0~ 911al 1011bl 1111bl Fig. 4. Crown ethers of different 1211bl ring size a) Ring-stiffened aryl ether ligands (Fig. 3) 5.9-10): Basicity and donor ability of the oxygen atoms are reduced (4-8). b) Varied ring size (Fig. 4) 5,11): Every number of ring members and oxygen donors is possible (9-13). c) Geometric arrangement of the donor atoms in the ring (Fig. 5) 5,12): The oxygen atoms can be separated (14, 15) or brought together (16-18). d) Sulfur as -alternative donor site (Fig. 6) 13,14): All O,S-sequence combinations (19-22) and even pure thiacrowns like 23 are possible. e) Nitrogen as donor site (Fig. 7) 15): Incorporation of any number of N-atoms into the ring and at any position is possible (24-28). 6