Calixarene Carbamates

FULL PAPER

Calixarene Carbarnates Burkhard Konig"", Tom Fricke", Ina Dixb, Peter G. Jonesb, and Iris Thondorf'

Institut fur Organische Chemie der Technischen UniversitHt Braunschweig", Hagenring 30, D-38 106 Braunschweig, Germany E-mail: [email protected] Institut fur Anorganische und Analytische Chemie der Technischen Universitat Braunschweigb, Postfach 3329, D-38023 Braunschweig, Germany Institut fur Biochemie der Martin-Luther-Universitat Halle", D-06099 Halle, Germany

Received June 25, 1997

Keywords: Calixarenes / Macrocyclic ligands / Molecular recognition / Molecular modelling / Supramolecular chemistry ~

Calixarene carbamates were obtained in good yield from the clean reaction of n-butyl isocyanate with para-tert-butyl-calix[4]-, - [6]- , and -[8]arenes. Whereas the two larger calixarenes remain mobile in solution upon derivatisation, para-tert- butyl-calix[4]arene is locked in the cone conformation. A selective triple acylation was observed with Li,CO, as base, whereas K2C03 leads to complete functionalisation of all hy-

droxy groups. The relative stability of all possible conformers of calix[4]arene tetracarbamate (1) was examined by force field calculations, showing the cone conformer as the most stable one. The structures of compounds 1 and 3 were investigated by X-ray structure analysis, confirming the cone conformation for both compounds.

The rational design of specific receptors for selective binding is a field of growing interest in supramolecular chemistry. It is therefore important to develop three-di- mensional platforms for the attachment of functional groups that can be oriented to form a suitable binding site. In particular, calix[4]arene, L2] a cyclic tetramer of phenolic units linked via the ortho positions by methylene bridges, is recognized as such a molecular building block. L31 Calix[4]arene is readily available from cheap starting materials, and it can be easily functionalized at the phenolic OH groups (lower rim) as well as at the puru positions of the phenol ring (upper rim). One of the most important and unusual properties of calix[4]arene is the ability to adopt four different extreme conformations. This is an advantage, since it enlarges the number of potential useful geometries; however the conformations must also be controllable. When all four phenolic OH groups of calix[4]arene are replaced by large substituents, conformationally fixed derivatives are obtained, generally as a cone, partial cone, 1,2-, 1,3-alternate, or sometimes a mixture of these conformations. [2a] Whereas alkylation reactionsL4I and acid- or base-catalyzed acyla- tions with acyl halidesC5I have been investigated in detail, the well-known reaction of hydroxy groups with isocyan- ates16] has not been used for selective calixarene derivatiza- tion. We report here the synthesis of p-tert-butyl-calix[4]-, -[6]-, and -[8]arene carbamates from isocyanates, the control of the p-tert-butyl-calix[4]arene conformation in this acylation reaction and the selective synthesis of a triply acylated calix[4]arene derivative.

For alkylation and acylation of phenolic hydroxy groups of calix[4]arene, reaction conditions are established that

give cone, partial cone, or 1,3-alternate conformations selec- tively. In these reactions all factors that increase the rate of alkylation or acylation, e.g. alkylating reagent, solvent polarity, cation of the base, or decrease the rate of ring inversion, e.g. by templating cations, favour the cone conformation over the others. Therefore, the exclusive formation of cone-1 from reaction of the highly reactive n-butyl isocyanate with 2 in the presence of K2C03 is expected. To investigate the influence of metal cation, base, and solvent the reaction was performed with Li2C03, Na2C03, or K2C03 in acetone or acetonitrile. Table I summarizes the results: Whereas the variation of the solvent changes the overall yield only slightly within the error limits of the experiment, the use of different bases results in the formation of different major products. With decreasing size of the base coun- terion the triply acylated cone-3 becomes the major reaction

The best selectivities were observed in acetone: with K2C03 as base 1 is the only product, whereas Li2C03 leads to a 9:l selectivity in favour of 3. Without added base no reaction takes place under these conditions.

The electrospray ionisation mass spectra (ESI) of 1 and 3 show intensive signals of the corresponding alkali metal cation complexes, with sodium as the most intensive. [*I We have therefore investigated the ability of 1 and 3 to extract metal salts into organic solvents or to act as carriers for the transport of salts through supported liquid membranes. L91 However, neither competitive salt extraction experiments,['Ob1 nor competitive ion along a step concentration gradient or pH driven transport experiments["] showed significant transport rates or selectivities.

Liebigs Ann.lRecueil1997,2315-2320 0 WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1997 0947-3440/97/1111-2315 $17.50+.50/0 2315

FULL PAPER B. Kiinig, T. Fricke, I. Dix, P. G. Jones, I. Thondorf

Table 1. Product ratio of the reaction of 2 with n-butyl isocyanate with various bases in acetone and acetonitrile

base solvent ratio 1 : 3 overall yield

K,CO,'"' acetone 100 : 0 83% acetonitrile 85 : 15 79%

Na,CO,["l acetone 60 : 40 68% acetonitrile 65 : 35 66 %1

Li,CO,['l acetone 10 : 90 84% acetonitrile 40 : 60 75%

["I Reaction at room temp. - cb] Reaction under reflux.

Hexahydroxy-para-tert-butylcalix[6]arene (4) and octahydroxy-paru-trrt-butylcaIix[8]arene (5 ) were converted to the carbamates 6 or 7 in acetone with Na2C03 and excess n- butylisocyanate. The complete conversion of all hydroxy groups was confirmed by detection of molecular ions at in/= = 1568 or 2091 in the mass spectra.["] The NMR spectra of both compounds are poorly resolved at room temperature indicating strong intramolecular hydrogen bonding. Neither the addition of methanol nor the use of competitive solvents, such as pyridine, improves the resolution. However, a well resolved spectrum was obtained for 7 at 90°C in C2D2C14.

291.6(5) pm [N35-H35'...074 156(4)"] and N55...074 311.2(5) pm [N55-H55'...074 170(4)"]. Three of the carbamate nitrogen atoms (N15, N35, and N55) and the carbonyl oxygen 074 are nearly coplanar (mean deviation from plane: 4 pm). Two molecules of ethanol and one of water cocrystallize with 1. The solvent molecules are disordered.

The crystal structure analysis of 3 confirms the consti- tution and conformation of the compound. The calix[4]arene core shows a cone conformation. The hydroxy group of the non-acylated calix[4]arene ring points into the cavity with hydrogen bonds to the hydrogen at N55 [N55...012: 305.6(5) pm, 012...H55'-N55: 132(3)"] and 072 [012...072: 284.0(4) pm, 012-H12'...072: 175(5)"]. An in- termolecular hydrogen bond was observed between two calixarene molecules: H35...054 (-x + 1/2, -y + 3/2, -z): 228(6) pm; N35-H35'...054: 149(5)". Surprisingly 4- hydroxy-4-methylpentan-2-one, the product of an acetone aldol reaction, was found in the crystal. Hot acetone was used for crystallization. A careful GC analysis of the employed solvent showed that it contains traces of 4-hydroxy- 4-methylpentan-2-one and 4-methylpent-3-en-2-one in equal amounts. Therefore the inclusion of the aldol product in the crystal is a highly selective process."']

) Force Field Calculations \

All calculations were performed on the N-methyl analogue of 3 in order to save computation time. A multitude of structures within the relatively narrow energy range of 5 kcal mol- ' abovc the respective lowest energy structure was obtained: 28, 43, 31, and 32 individual conformers in the cone, partial cone, 1,2- and 1,3-alternate arrangements, [2"]

respectively. This might be an indication of the flexibility of the molecule under study: although the bulky urethane functions prevent ring inversion processes of the calixarene

) H N

!-0 N=C=O

6 11 - 6 56 Y o I 11 L 8 60 %

rn & Na,CO,, acetone - m 1 11 6 5 11-8

X-ray Structure Analysis

The X-ray structure analysis of 1 confirms the proposed cone conformation of the calix[4]arene core. In the solid state three of the carbamate carbonyl groups point out- uards from the calix[4]arene cavity, whereas the fourth car- bony1 group is placed above the central cavity. A network of intramolecular hydrogen bonds between this carbonyl oxygen, the carbamate N-H protons and the carbamate ovygens attached to the arenes stabilizes the observed conformation. The hydrogen on N15 forms a hydrogen bond to the carbonyl oxygen with a distance N15...074 of 323.0(5) pm [N15-H15'...074 142(4)"]. The two other hydrogen bonds to the carbonyl group are shorter: N35...074

framework, the inclination of aryl rings to the average plane of the four methylene carbons differs significantly among the low energy conformers. The corresponding angles from X-ray structure analysis are: 52, 87, 51, and 83". Moreover, the upper and lower rim substituents can assume various arrangements. The amide bond adopts a trans orientation (0-C-N-C ca. 180") in all low energy conformers. The corresponding angles from X-ray structure analysis are:

-179.8(4), 012-CI3-Nl5-Cl6: -176.1(4), and 072-C73-N75-C76: 171.1(5)". Both the cis and trans configuration were found for the ester bond [C-0-C( = 0)-N]. The X-ray structure shows corresponding values of

032-C33-N35-C36: 178.7(3), 052-C53-N55-C56:

C21-032-C33-N35: -178.2(3), C41-052-C53-N55:

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FULL PAPER Calixarene Carbamates

Figure 1. Structure of 1 in the solid state. Solvent molecules have been omitted for clarity. tert-Butyl groups C8, C48, and C68 are

disordered over two orientations, of which only one is shown

c19

Figure 2. Crystal structure of 3. The atoms C36 to C39 are disordered over two positions, of which only one is shown

C6

165.3(3), Cl-012-Cl3-Nl5: -163.0(3), and C61-072-C73-N75: -435)". MM3 calculations of N- methyl- O-phenyl urethane indicate an energy difference of 1.8 kcal mol-' for the two extremes (0' and 180"). The truns-0- C-N-C and cis-C-0 - C( =0) -N configuration of the urethane moieties leads to an inward orientation of the carbonyl group in 1, whereas in the trunsltruns configuration the N-H bond points to the interior of the cavity formed by the lower rim substituents. Thus, the values of the C-0-C-N dihedral angles are related to the number and position of hydrogen bonds.

The stability of the four basic conformations decreases in the order cone > partial cone > I ,2-alternate > I ,3-alternate which roughly parallels the number of intramolecular hy-

drogen bonds in the lowest energy structures: 3 in the cone, 2 in the partial cone and 1,2-alternate, and 0 in the 1,3- alternate arrangement. The hydrogen bonds in the cone conformer are formed between a carbonyl oxygen (trans1 cis urethane) and the proximal and distal amide hydrogens (trunsltrans urethanes). (Figure 3a) A cone structure bear- ing two translcis and two trunsltruns urethane moieties, which results in the formation of four hydrogen bonds, is 1.06 kcal mol-' higher in energy.[l41

The energies listed in Table 2 indicate that various factors contribute to the relative energies of the conformations. The steric crowding of the bulky lower rim substituents mainly accounts for the unfavorable nonbonding energies of the cone- compared to the partial cone- and 1,2-alternate-conformers, whereas the superior stability of the core results from advantageous bonding interactions.

As shown in Figure 3b, two hydrogen bonds are formed in the partial cone conformer between a carbonyl oxygen and its two adjoining amide groups. The urethane moiety

Liebigs Ann.lRecuei1 1997, 2315-2320 2317

B. Konig, T. Fricke, I. Dix, P. G. Jones, I. Thondorf FULL PAPER Table 2. Relative energies [kcal mol-'1 and geometric parameters of the lowest energy conformers

conformer FSEr.II ZEbobond ZEnhond C-0-C-N dihedral angle [deg]

0-C-N-C dihedral angle [deg]

cone -3.54 (0.00) -12.28 8.74 -2 -157 -180 155 180 180 180 180

1,2-rrlt -1.14 (2.40) -1.21 0.07 -136 -138 -134 -156 178 180 180 176 1,3-trlr 3.92 (7.46) -12.19 16.11 167 172 170 176 -180 180 -180 180

puco -2.39 (1.15) -5.92 3.53 161 -3 -162 -23 -179 -180 180 -176

b The abbreviations denote the following: FSE final steric energy, CEbond sum of all bonding energies, ZEnbo,,d sum of all nonbonding energies.

(tvundcis configuration) of the ring that is oriented unti to the rest of the rings is situated inside the cavity formed by the aryl residues, so that the higher energy of the cis arrangement is compensated by the nonbonded interactions.

Figure 3. Orthogonal views of the lowest energy structures of the cone (a), partial cone (b), 1,2-alternate (c), and 1,3-alternate (d) conformations. Hydrogens bonded to carbon atoms are omitted for

clarity. Hydrogen bonds are represented by broken lines

f

In the 1,2-alternate arrangement (Figure 3c) the carbamate groups show deviations from planarity (C-0-C-N dihedral angles 130- 160') due to hydrogen bonding between adjacent syn oriented rings. This leads to high torsional energies which are partly balanced by the favorable nonbonding energy contributions. The 1,3-alternate conformer (Fig- ure 3d) reveals a similar bonding energy to the cone structure; however, because of repulsive interactions between the urethane moieties and the tevt-butyl groups and the lack of intramolecular hydrogen bonding it is the least stable.

The similarity of the structure of 1 determined by X-ray structure analysis compared to the calculations on the N - methyl analogue is striking. The force field estimates the average hydrogen bond to be a little shorter, and the in- creased inclination of two phenyl rings to the average plane of the four methylene groups to a pinched cone conformation is more developed in the X-ray structure(force field/ X-ray 51/52'; 75/87; 51/51; 74/83"). The deviation of all cal- culated angles given in Table 2 from the X-ray data is less than 10°.[15] The comparison of the calixarene framework structures from X-ray crystallography aFd force field calculations gives an rms deviation of 0.16 A for non-hydrogen atom positions.

This work was supported by the Fonds der Clzemischen Industrie. We thank M. Miiller for ICP-AES measurements and Dr. M. Nimtz for mass spectra.

Experimental Section Melting points were taken on a hot-plate microscope apparatus

and are not corrected. - NMR spectra were recorded at 400 MHz ('H) and 100 MHz ('IC) in [D]chloroform solueft hyphentions unless otherwise stated. The multiplicity of the I3C signals was determined with the DEPT technique and quoted as: (+) for CH3 or CH, (-) for CH2, and (Cquat.) for quaternary carbons. CC means column chromatography on silica gel unless otherwise stated. Transport experiments were performed with AccurePlortho-nitro- phenyl octyl ether membrane and a mxiture of ten nitrate salts (each 120 mmolll). For conditions and membrane preparation, see

X-ruy Structure Determinutions

Crystal Structure Anulysis of Compound [1.2 (EtOH) . (H,O)]: Crystal datu: C68H98N4011r M, = 1147.50, triclinic, space group P i , u = 1466.4(3), h = 1544.7(3), c = 1593.3(3) pm, a = 71.47(2),

= 83.63(2), y = 86.94(1)", V = 3.4001 nm3, Z = 2, D, = 1.082 Mg m-3, h (Mo-K,) = 71.073 pm, p = 0.070 mm - I , T = - 100°C. Data collection und reduction: An irregular colourless prism 0.75 X

0.40 X 0.26 mm was mounted in inert oil on a glass fibre and transferred to the cold gas stream of the diffractometer (Siemens-

2318 Liebigs Ann.lRecueill997, 2315-2320

FULL PAPER Calixarene Carbamates

P4 diffractometer with LT-2 low temperature attachement). 11931 intensities (1 1812 unique, Hint 0.028) to 20,,, = 50" were measured with the o-scan method. Structure solution and refinement: The structure was solved by direct methods and refined anisotropically on P using the program SHELXL-93 (G. M. Sheldrick, University of Gottingen). The carbamate N-H protons were refined freely. The other hydrogen atoms were included as a rigid hydroxy group or with a riding model. The final wR(F) was 0.223 for all reflec- tions and 797 parameters, conventional R(F) 0.078. The weighting scheme was u' = [oze + (up)* + bP)-'], where P = (F; + 2/3 F 3/3 and a, b are constants optimised by the program. S = 0.87; max. A/o < 0.001; max. Ap = 880 e nmP3.

Crystal Structure Analysis of' Compound [3. (C6HI2O2)]: Crystal datu: CG5Hg5N309, iM, = 1062.44, monoclinic, space group C2/c, u = 2727.2(6), b = 1790.8(4), c = 2746.7(5) pm, fi = 108.84(2)", V = 12.696 nm3, Z = 8, D, = 1.112 MgmP3, p = 0.073 mm - I ,

T = - 100°C. Data collection and reduction: Colourless tablet 0.68 X 0.62 X 0.20 mm, 18846 data, 11 143 unique (Ri,lt 0.0540). Struc- ture refinement: Final wR(F) 0.229 for 712 parameters, R(F) 0.076, S = 0.88; max. Ap = 711 e nm-3 . The carbamate N-H protons and the hydroxy group OH(12') were refined free. The other hydrogen atoms were included as rigid hydroxy group OH(99) and rigid methyl groups (C94, C98, C99) or with a riding model. All other details as above.

Full details of the crystal structure determinations (except structure factors) have been deposited under the number 100493 at the Cambridge Crystallographic Data Centre. Copies may be obtained free of charge from: The Director, CCDC, 12 Union Road, GB- Cambridge CB2 IEZ (Telefax: Int. +44 (0)1223/336-033; E-mail: [email protected].

Speciul Features of' Refinement: The tert-butyl groups C8, C48, and C68 of 1 are disordered over two orientations of occupancy 0.54(1) and 0.46(1). Three solvent molecules cocrystallize with 1. One ethanol molecule can be determined reliably. The distances between the remaining peaks indicate one further ethanol and one water molecule. The latter molecules can only be refined isotropically and the highest residual electron density is found next to C96 and C97.

The high temperature factors of the tert-butyl groups of 3 may indicate disorder of these groups. Furthermore two carbamate n- butyl groups show disorder. The group C36 to C39 is refined at two positions with occupancies of 0.70(1) and 0.30(1). The other group C76 to C79 can only be refined isotropically (one position). The highest residual electron density is found near to this group.

Because both crystals diffract weakly, a system of restraints (834 for 1 and 712 for 3 in all) to the light atom displacement parameter components was employed to improve the refinement stability.

Force- Field Calculations

Methods: All calculations were performed using the MM3(94) force field[16] running on SGI Indigo2 workstations. In order to locate minima on the energy hypersurface, a conformational search using the stochastic search subroutine['7] of MM3 was performed, starting from each of the four main conformations (cone, partial cone, 1,2- and 1,3-alternate). This approach moves atoms randomly and the resulting structure is energetically minimized. Since in MM3 the full-matrix Newton-Raphson minimization scheme is limited to 120 atoms, the block-diagonal Newton-Raphson method was applied. Missing torsional and angle bending parameters for the urethane moiety were generated using the MM3 parameter esti- mator and used without further modification. The default values for the input parameters of the stochastic search were employed.

The search was considered to be finished if each of the conformers within the range of 5 kcal mol-' above the lowest energy structure was found at least twice.

Culix[4]arene 1: n-Butyl isocyanate (1.0 ml, 9.0 mmol) was added to a suspension of tetrahydroxy-paru-tert-butylcalix[4]arene (1 .O g, 1.5 mmol) and K2C03 (2.1 g, 15 mmol) in 70 ml of dry acetone under nitrogen. The reaction mixture was stirred at room temp. for 16 h and the solvent was removed in vacuo. 20 ml of CHzCl2 were added, the suspension was filtered, washed with sat. NH4CI, dried over Na2S04 and the solvent was evaporated. Recrystallization of the crude product from n-heptane (20 ml) gave 1.3 g (83%) of pure 1 (Rf = 0.40 in CH2C12/MeOH, 99:1), as a white solid, m.p. > 300°C. - IR (KBr): i j = 3420 cm-I, 1740, 1690, 1530. - UVlVis (CH3CN): h,,, (lg E) = 194 nm (5.03), 228 (4.45). - 'H NMR (400 MHz, CDC13): 6 = 6.93 (s, 8 H), 6.27 (bs, 4 H), 3.89 (d, ' J = 13.1 Hz, 4 H), 3.33 (1, ' J = 6.8 Hz, 8 H), 3.27 (d, 2J = 13.5 Hz, 4 H), 1.63 (m, 8 H), 1.43 (m, 8 H), 1.09 (s, 36 H), 0.98 (t, ' J = 7.4 Hz, 12 H). - I3C NMR (100 MHz, CDC13): 6 = 156.2 (Cquat), 147.8 (Cquat.), 143.3 (Cquat.), 133.6 (Cquat.), 125.3 (+), 41.2 (-), 34.0 (Cquat,), 32.2 (-), 31.2 (+), 31.0 (-), 20.0 (-), 13.8 (+). - MS (ESI); m/z (%I): 1067.7 (100) [M + Na]', 1083.7 (10) [M + K]+, 1045.7 (15) [M + HI+, 542.3 (55) [M + K]'+. - C64H92N408 (1045.5): calcd. C 73.53, H 8.87, N 5.36; found C 73.40, H 9.17, N 5.46.

Culix[4]arene 3: To a suspension of tetrahydroxy-puru-tert-butylcalix[4]arene (1 .O g, 1.5 mmol) and Li2C03 (1.1 g, 15 mmol) in 70 ml of dry acetone under nitrogen was added n-butyl isocyanate (1.0 ml, 9.0 mmol). The reaction mixture was refluxed for 16 h and worked up as described for 1. The crude product was purified by CC (CH2C12/MeOH, 99:1, Rf = 0.67) to yield 1.1 g (77%) of 3 as a white solid, m. p. > 300 "C. - IR (KBr): i j = 3530 cm-', 3390, 1740, 1700, 1520. - UVNis (CH3CN): h,,, (Ig E) = 196 nm (5.04),

(s, 2 H), 6.80 (d, 4J = 2.2 Hz, 2 H), 6.73 (d, 4J = 2.2 Hz, 2 H), 5.82 (bs, 3 H), 5.30 (bs, 1 H), 4.06 (d, ' J = 13.7 Hz, 2 H), 3.92 (d, ' J = 13.2 Hz, 2 H), 3.39 (d, 'J = 13.7 Hz, 2 H), 3.35 (m, 6 H), 3.29 (d, 2J = 13.3 Hz, 2 H), 1.62 (m, 6 H), 1.43 (m, 6 H), 1.28 (s, 9 H), 1.28 (s, 9 H), 0.98 (m, 9 H), 0.95 (s, 18 H). - I3C NMR (100

224 (4.55). - 'H NMR (400 MHz, CDC13): 6 = 7.15 (s , 2 H). 7.05

MHz, CDC13): 6 = 155.6 (Cquat), 154.9 (Cqnat,), 149.7 (Cquat,), 147.9 (Cquat 1, 144.3 (Cqwat.), 142.8 (Cquat.1, 142.7 (Cquat.), 134.7 (Cquat), 132.8 (Cquat.), 132.1 (Cquat.1, 128.9 (Cquat.17 125.8 125.5 (+), 125.3 (+), 41.8 (-), 41.1 (-), 34.3 (Cquat.), 33.9 (Cquat,)? 33.9 (CquI,t), 32.5 (-), 32.2 (-), 32.0 (-), 31.6 (+), 31.4 (+), 31.3 (-), 31.2 (-), 31.0 (+), 20.2 (-), 19.9 (-), 13.8 (+), 13.7 (+). - MS (ESI); m/z (%I): 968.6 (100) [M + Na]+, 946.7 (5) [M+]. - C59Hs3N307 (946.3): calcd. C 74.88, H 8.84, N 4.44; found C 75.07, H 8.99, N 4.29.

Cali-x[6]arene 6: n-Butyl isocyanate (1 .O ml, 9.0 mmol) was added under nitrogen to a suspension of hexahydroxy-puru-tert-butylcalix[6]arene (1.0 g, 1.0 mmol) and Na2C03 (1.6 g, 15 mmol) in 70 ml of dry acetone. The reaction mixture was stirred for 16 h at room temp. and worked up as described for 1. CC (CHZCIz/MeOH, 99:l; Rf = 0.37) yielded 0.91 g (56%) of 6, as a white solid, m.p. 151-155 "C. - IR (KBr): i j = 3420 cm-I, 1740, 1520. - UV/Vis (CH3CN): h,,, (lg E) = 196 nm (5.26), 220 (4.90). - MS (ESI);

C96H138N6012 (1568.2): calcd. C 73.53, H 8.87, N 5.36; found C 73.23, H 9.06, N 5.32.

Cu/ix[8]arene 7: To a suspension of octahydroxy-paru-tert-butylcalix[8]arene (1.0 g, 0.77 mmol) and Na2C03 (1.6 g, 15 mmol) in 70 ml of dry acetone was added n-butyl isocyanate (1.0 ml, 9.0 mmol). The reaction mixture was stirred for 16 h at room temp.

W?/Z (9'0): 1589.7 (100) [M + Na]+, 1567.7 (30) [M + HI+. -

Liebigs Ann.lRecueill997, 2315-2320 2319

FULL PAPER B. Konig, T. Fricke, I. Dix, l? G. Jones, I. Thondorf

and workcd up as described for 1. CC (CH2CI2/MeOH, 99:1, R,. = 0.30) gave 0.96 g (60'K) of 7, as a white solid, m.p. 160 "C. - IR (KBr): G = 3360 cm-', 1740, 1530. - UVIVis (CH,CN): h,,, (lg E ) = 196 nm (5.39). 220 (5.08). - ' H NMR (400 MHz, C2D2Cl4,

(m. 16 H), 1.53-1.13 (m. 104 H), 0.84 (t, 3J = 7.3 Hz, 24 H). - I3C NMR (100 MHz, C2D2CI4, 90 "C): 6 = 154.3 (C,,,,), 148.0 (C,,,c,,L 145.5 (Cquat), 132.6 (Cquat), 125.8 (+), 41.2 (-), 34.2

90 "C): 6 = 6.97 (s. 16 H), 4.94 (bs, 8 H), 3.73 (s, 16 H), 3.13-3.05

(C,,,,,), 31.9 (-), 31.4 (+), 31.3 (-), 19.8 (-), 13.5 (+). - MS (MALDI-TOF); /??I: ('%I): 21 14 (7.5) [M + Na]+, 2130 (100) [M + K]'. - C128H184NROlh (2090.9): calcd. C 73.53, H 8.87, N 5.36; found C 73.68, H 9.09, N 5.45.

[ ' I ['"I J.-M. Lehn. Suprat~iolecular Chemistry, VCH, Weinheim 1995. - [ I b ] F. Vogtle, Supramolekulure Chemie, Teubner, Stuttgart 1991. - [''I D. S. Lawrence, T. Jiang, M. Levett, Chem. Rev. 1995, Y5, 2229-2260. - [Id] J.-M. Lehn, Pure Appl. Chem. 1994, 66, 1961-1966. - ["I B. Konig, J Prakt. Chem. 1995, 337, 339-346. - ''0 A. D. Hamilton (Ed.), Molecular Recog- rzition, Tetrcrhedron, Symposia in print No. 56, 1995, 51. Recent examples: U. Neidlein, F. Diederich, C'hem. Commun. 1996, 1493-1494. - I ' h ] P. Schiessel, F. P. Schmidtchen, J. Org. Chem. 1994, 59, 509-511. - ["I M. S. Goodman, V. Jubian, A. D. Hamilton, Tetrahechon Lett. 1995, 36, 2551-2554. - [lJl T. Mi- zutani, T. Murakami, T. Kurahashi, H. Ogoshi, J Org. Chein.

[','I For the description of calix[4]arene conformations see: C. D. Gutsche, C'u1i.vurene.s in Monographs in Supramolecular Chemistry (Ed.: J. F. Stoddart), The Royal Society of Chemis- try, Cambridge, 1992. - [2b] V. Bohmer, Angew Chem. 1995, 107, 785-818; Angriv. Chem. Int. Ed. Engl. 1995, 34, 713-745.

['I ['"I L. C. Groenen, D. N. Reinhouldt, in Supramolecular Chem- istry (Eds.: V. Balzani, L. DeCola), Kluwer, Dordrecht, 1992, 51 -70. - [3hl A. Ardani, A. Casnati, M. Fabbi, A. Minari, A. Pochini, A. R. Sicuri, R. Ungaro, ihid. 1992, 31-50. - LDC] R. Ungaro. A. Pochini, in Frontiers in Supramolecular Organic C hernistry cind Photochemistry, (Eds.: H.-J. Schneider, H. Diirr), VCH, Weinheim, 1991, 57-81. - Calixarenes in defined conformations as selective ionophors: [3d1 E. Ghidini, F. Ugozzoli, R. Ungaro, S. Harkema, A. A. El-Fadl, D. N. Reinhouldt, J. An?. Chern. Soc. 1990, 112, 6979-6985. - [3e] R. Ungaro, An- grit: C/7~m. 1994, 106, 1551-1553; Angew. Chem. Int. Ed. Engl.

L4] L4"1 C. D. Gutsche. Acc. Clzem. Res. 1983, 16, 161-170. - [4b1 C. D. Gutsche, Top. Curr. Chem. 1984, 123, 1-48. - [4c1 J.-D. van Loon, W. Verboom, D. N. Reinhoudt, Org. Prep. Proceed. Int. 1992, 24, 437. - [4d1 S. Shinkai, Tetrahedron 1993, 49, 8933-8968. - A. Pochini, R. Ungaro, in Comprehensive Suprariiolecular Chemistry (J. L. Atwood, J. E. D. Davies, D. D. Macnicol, F. Vogtle, J.-M. Lehn, Eds.), Vol 2, Pergamon, Ox- ford, UK, 103-142. M. Iqbal, T. Mangiafico, C. D. Gutsche, Tetrahedron 1987, 43,

Ihl r5;'1 P. A. Grieco. W. A. Carroll, Tetrahedron Lett. 1992, 33, 4401 -4404. - X.-F. Pei, N. H. Greig, J. L. Flippen-Ander- son, S. Bi, A. Brossi, Helv Chitn. Acta 1994, 77, 1412-1422.

Q. YLI, B. Lu, X.-F. Pei, Heterocycles 1994, 39, 519-525. Ba(OH)? has been used for the selective triple acylation of tetrahydroxy-pnra-tert-butyl calix[4]arene. However, this base was

1996, 6 1 , 539-548.

1994, 1506-1509.

49 17-4930.

not suitable for a selective acylation with n-butyl isocyanate. [7a1 C. D. Gutsche, B. Dhawan, J. A. Levine, K. H. No, L. J. Bauer, Tetrahedron 1983, 39, 409-426. - [7b1 K. Iwamoto, A. Yanagi, T. Arimura, T. Matsuda, S. Shinkai. Chem. Lett. 1990, 1901-1904. - L7'1 S. Shinkai, T. Arimura, H. Kawabata, H. Murakami, K. Araki, K. Iwamoto, T. Matsuda, J Chem. Soc., Chem. Commun. 1990, 1734-1736. - [7d1 K. Iwamoto, A. Yan- agi, K. Araki, S. Shinkai, Chem. Lett. 1991, 473-476. - [7el K. Iwamoto, K. Araki, S. Shinkai, Tetruhedron 1991, 47, 4325-4342. - L7g Triply acylated calixarenes have been isolated in small yields from the reaction with acyl chlorides. See ref.[5]

Several calixarene amides are strong ionophores. M. A. McKervey, M.-J. Schwing-Weill, F, Arnaud-Neu in Comprehen- sive Supramolecular Chemistry (J. L. Atwood, J. E. D. Davies, D. D. Macnicol, F. Vogtle, J.-M. Lehn, Eds.), Vol 1, Pergamon, Oxford, UK, 1996, pp. 537-603. - L R b ] The cocrystallisation of 1 and 3 with alkalimetal salts under various conditions were not successful.

L91 For reviews of this topic, see: LYal F. de Jong, H. C. Visser, in Comprehensive Supramolecular Chemi,Qry, Vol 10 (Eds.: J.-M. Lehn, J. L. Atwood, J. E. D. Davies, D. D. Macnicol, F. Vogtle, D. N. Reinhoudt), Pergamon, Oxford, 1996, pp. 13-51. - [9b1 W. F. van Straaten-Nijenhuis, F. de Jong, D. N. Reinhoudt, Recl. Trav. Chim. Pays-Bas, 1993, 112, 317-324. - ["I H. C. Visser, D. N. Reinhoudt, F. de Jong, Chem. Sor. Rev. 1994, 23, 75-81. - [9d1 J. D. Lamb, J. J. Christensen, R. M. Izatt, J. Chem. Ed. 1980, 57, 227-229. - Lye] J.-M. Lehn, Pure Appl. Chem. 1979, 51, 979-997. - r9fl L. F. Lindoy, D. S. Baldwin, Pure A

experiments a source phase containing several nitrate salts is used. The salt content of the receiving phase (or the extracted aqueous phase) is analyzed by inductively coupled plasma atom emission spectroscopy (ICP-AES). This procedure allows the investigation of the transport pattern of a compound under given conditions in a single experiment. B. Koni M. Bahadir, M. Miiller, H. Wichman, unpublished results. -qiob] B. Konig M. Rodel, P. Bubenitschek, P. G. Jones, I. Thondorf, J: Org.' Chew. 1995, 60, 7406-7410.

["I pH-driven transport: R. M. Izatt, G. C. LindH, R. L. Bruening, J. S. Bradshaw, J. D. Lamb, J. J. Christensen, Pure Appl. Cheni.

[ I2] As in the case of the smaller calixarene carbamates, 6 and 7 show intensive molecular ions of their alkali metal complexes in mass spectra. Their transport ability was testcd in membrane transport of metal salts giving no significant activity. A solution of 3 in acetone was refluxed to investigate a possible catalysis of the aldol reaction under neutral conditions. How- ever, GC analysis showed that no additional aldol addition product was formed under these conditions. For a recent ex- ample of the use of calixarenes as catalysts see: N. Pirrincioglu, F. Zaman, A. Williams, J. Chern. Soc., Perkin Trans. 2 1996,

[141 A dihedral angle driver calculation with MM3, which trans- formed the lowest energy conformer into this conformer, re- vealed a barrier of 9.9 kcal mol-'.

[151 The calculations were performed independently without the use of experimental data.

[ I6 ] N. L. Allinger, Y. H. Yuh, J.-H. Lii, J. Am. Chem. Soc. 1989, 111, 8551-8566. - [16b] J.-H. Lii, N. L. Allinger, J. Am. Chem. Soc. 1989, 8566-8575. - [I6'] J.-H. Lii,. N. L. Allinger, .I Am. Chem. SOL: 1989, 8576-8582.

1'1

I Cheni. 1989, 61, 909-914. ['"I [ I f7 a In ' competitive salt extraction experiments or ion transport

1986, 58, 1453- 1460.

2561-2562.

["I M. Saunders, J. Am. Chem. Soc. 1987, 109, 3150-3152. [97189]

2320 Liebigs Ann.lRecueill997, 2315-2320

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Calixarene Carbamates