Showing papers by "J. Fraser Stoddart published in 1982"

Conformational behaviour of medium-sized rings. Part 11. Dianthranilides and trianthranilides

Abstract: Two approaches to the stepwise syntheses of N,N′-di- and N,N′,N″-tri-substituted trianthranilide derivatives (5)–(20) are described. In the shorter synthetic route, the key acyclic intermediate, N-[2-(o-nitrobenzamido)benzoyl]anthranilic acid (26) is prepared in a stepwise manner from anthranilic acid, isatoic anhydride (23), followed by o-nitrobenzoyl chloride. Alkylations of the amide functions at nitrogen, reductions of the aromatic nitro-groups, and cyclisations of the acyclic amino-acid derivatives provide a direct route to N,N′-dimethyl-(5) and N,N′-dibenzyl-(14) trianthranilides. Further alkylations or acylations of either (5) or (14) afford (i)N,N′,N″-trimethyltrianthranilide (7) and its trideuteriomethyl analogue (8), (ii)N,N′-dimethyl-N″-acetyl-(10), -N″-benzoyl-(11), and -N″-benzyl-(12) trianthranilides, (iii)N,N′,N″-tribenzyltrianthranilide (15), and (iv)N,N′-dibenzyl-N″-methyltrianthranilide (16). In the longer synthetic route, the key acyclic intermediate, methyl N-methyl-N-[2-(o-nitrobenzamido)benzoyl]anthranilate (42) is prepared in a stepwise manner from anthranilic acid and two molar equivalents of o-nitrobenzoyl chloride. Alkylations of the unsubstituted amide functions at nitrogen, reductions of the aromatic nitro-groups, and cyclisations of the acyclic amino-acid derivatives provide, not only an alternative route to N,N′-dimethyltrianthranilide (5) but also, a general route to the N-methyl-N′-trideuteriomethyl-(6), N-methyl-N′-benzyl-(17), and N-methyl-N′-ethyl-(19) analogues. Further alkylations of these N,N′-disubstituted derivatives afford N-methyl-N′,N″-di(trideuteriomethyl)-(9), N-methyl-N′-trideuteriomethyl-N″-benzyl-(13), N-methyl-N′-benzyl-N″-ethyl-(18), and N-methyl-N′-ethyl-N″-benzyl-(20) trianthranilides.The constitutionally symmetrical N,N′,N″-trimethyl-(7) and N,N′,N″-tribenzyl-(15) trianthranilides exist in solution as an equilibrium mixture of propeller and helical conformations. In the case of the N,N′,N″-trimethyl derivative (7), the predominant diastereoisomer with the helical conformation has been isolated as a pure compound. In the case of the N,N′,N″-tribenzyl derivative (15), the propeller and helical conformational diastereoisomers have both been characterised as crystalline compounds. For both these compounds, the free-energy barriers to conformational inversion and interconversion processes in solution have been obtained from (i) direct equilibration experiments and (ii) dynamic 1H n.m.r. spectroscopy. Constitutionally unsymmetrical N,N′-di- and N,N′,N″-tri-substituted trianthranilide derivatives can adopt three helical conformations in addition to a propeller conformation. Assignments have been made to conformations and conformational diastereoisomers of the N,N′-dimethyl-(5), N,N′-dimethyl-N″-benzyl-(12), N,N′-dibenzyl-(14), N,N′-dibenzyl-N″-methyl-(16), N-methyl-N′-benzyl-(17), N-methyl-N′-benzyl-N″-ethyl-(18), N-methyl-N′-ethyl-(19), and N-methyl-N′-ethyl-N″-benzyl-(20) derivatives on the basis of (i) kinetically controlled trideuteriomethylations of N,N′-dimethyl-(5) and N-methyl-N′-trideuteriomethyl-(6) trianthranilides and (ii) a kinetically controlled benzylation of N,N′-dibenzyltrianthranilide (14). These experiments permit unambiguous site assignments to be made in the 1H n.m.r. spectra to (i) the homotopic N-methyl groups in the propeller conformation and the diastereotopic N-methyl groups in the helical conformation of N,N′,N″-trimethyltrianthranilide (7) and (ii) the homotopic N-benzylic-methylene groups in the propeller conformation and the diastereotopic N-benzylic-methylene groups in the helical conformation of N,N′,N″-tribenzyltrianthranilide (15). Correlations between site assignments and chemical shifts, for these two 1H n.m.r. probes, lead to conformational assignments to other N,N′-di- and N,N′,N″-tri-substituted derivatives. In most cases, free-energy barriers for conformational inversion and interconversion processes in solution could be obtained by dynamic, 1H n.m.r. spectroscopy. A satisfying complementary experimental approach is illustrated in the case of N,N′-dimethyltrianthranilide (5) where the occurrence of spontaneous resolution on crystallisation allows the barrier to racemisation to be measured by polarimetry.The temperature dependence of the 1H n.m.r. spectrum of 5,11,17-tribenzyl-6,6,12,12,18,18-hexadeuterio-5,6,11,12,17,18-hexahydrotribenzo[b,f,j][1,5,9]triazacyclododecine (22) can be interpreted in terms of ring inversion between enantiomeric helical conformations of this cyclic triamine. The barrier to conformational change is considerably lower than those for the N,N′,N″-trisubstituted trianthranilide derivatives.Variable-temperature 1H n.m.r. spectroscopy on N,N′-dibenzyldianthranilide (4) indicates that its eight-membered ring exists in enantiomeric boat conformations where ring inversion is slow on the 1H n.m.r. time scale even at +180 °C.Inclusion compounds are formed on crystallisation between (i) ethanol and N,N′-dimethyl-N″-benzyltrianthranilide (12) as a mixture of its conformational diastereoisomers, (ii) toluene and a helical conformation of N,N′-dibenzyltrianthranilide (14), (iii) ethanol and the helical conformation of N,N′,N″-tribenzyltrianthranilide (15), and (iv) ethanol and the helical conformation of 5,11,17-tribenzyl-6,6,12,12,18,18-hexadeuterio-5,6,11,12,17,18-hexahydrotribenzo[b,f,j][1,5,9]triazacyclodecine (22).

Conformational behaviour of medium-sized rings. Part 10. Dithiosalicylides and trithiosalicylides

Abstract: The trithiosalicylide derivatives (8)–(11) have been synthesised and shown by temperature-dependent 1H n.m.r. spectroscopy to exist in solution as ring inverting (35a)⇌(35b) enantiomeric helical conformations with trans-thioester linkages. The free energies of activation for these conformational changes are ca. 10 kcal mol–1 higher than those for the similar process in the corresponding trisalicylides. In contrast with the trisalicylides, the trithiosalicylides can only ring invert between enantiomeric helical conformations via intermediates containing a cis-thioester linkage. The dithiosalicylide derivatives (3)–(7) have been synthesised; the temperature dependence of the 1H n.m.r. spectrum of di-o-thiothymotide (7) has been interpreted in terms of ring inversion (40a)⇌(40b) between enantiomeric boat conformations. Comparison of the ΔG‡ value of 24.6 kcal mol–1 for this conformational change with that of 17.7 kcal mol–1 previously obtained for di-o-thymotide (41) suggests that cis-thioester linkages are subject to more resonance stabilisation than are cis-ester linkages.

Conformational behaviour of medium-sized rings. Part 12. Tri-3-methyltrianthranilide

Abstract: The stepwise synthesis of the N,N′-di- and N,N′,N″-tri-substituted tri-3-methyltrianthranilides (13)–(19) are described. The amino-acid derivatives (34), (38), and (45), which are the key acyclic precursors in the synthesis of the tri-3-methyltrianthranilides, were all prepared from 2-amino-m-toluic acid (22) and 2-nitro-m-toluoyl chloride as starting materials.Tri-3-methyltrianthranilide derivatives with three equivalent N,N′,N″-substituents can exist in either propeller or helical conformations. The N,N′,N″-trimethyl derivative (14) adopts enantiomeric helical conformations in solution and the barrier to ring inversion is 26.8 kcal mol–1. The N,N′,N″-tribenzyl derivative (19) populates both propeller and helical conformations in solution: these two conformational diastereoisomers have been separated by chromatography and isolated as crystalline compounds.Tri-3-methyltrianthranilide derivatives with two or three non-equivalent N,N′,N″-substituents can, in principle, exist in either propeller or three different helical conformations. One of these three helical conformations is specifically populated in deuteriochloroform solution by compounds (13) and (15)–(17). The N,N′-dibenzyl derivative (18) populates the propeller and one helical conformation in solution: two conformational diastereoisomers have been isolated, one as an oil and the other as a crystalline compound.The N,N′-dimethyl-N″-benzyl derivative (15) undergoes spontaneous resolution when it crystallises as a 1 : 1 adduct from toluene. The N-methyl-N′-benzyl derivative (16) also forms a 1 : 1 inclusion compound on crystallisation from toluene. Although this derivative exists as only one conformational diastereoisomer of the helical type in deuteriochloroform solution, two different diastereoisomeric conformations undergo equilibration in hexadeuteriodimethyl sulphoxide with a barrier to interconversion of 16.1 kcal mol–1.

Conformational behaviour of medium-sized rings. Part 14. Tetra-anthranilides

Abstract: The stepwise synthesis of N,N′,N″-trimethyltetra-anthranilide (13) is reported and the temperature dependence of the 1H n.m.r. spectrum of N-benzyl-N′,N″,N‴-trimethyltetra-anthranilide (15) is interpreted in terms of equilibration between three diastereoisomeric conformations in solution. Although there is 1H n.m.r. spectral evidence for the presence in solution at room temperature of at least six conformational diastereoisomers of (13), N,N′,N″,N‴-tetramethyltetra-anthranilide (14) appears to adopt a single conformation of high symmetry in solution.

Conformational behaviour of medium-sized rings. Part 15. 1,9,17-Triaza[2.2.2]metacyclophane-2,10,1 8-trione derivatives

Abstract: The stepwise synthesis of 1,9-dimethyl-1,9,17-triaza[2.2.2]metacyclophane-2,10,18-trione (1) from methyl m-aminobenzoate and m-nitrobenzoyl chloride is reported. The temperature dependences (i) of the 1H-decoupled 13C n.m.r. spectrum of the 1, 9,17-trimethyl derivative (2) and (ii) of the 1H n.m.r. spectrum of the 1,9-dimethyl-17-benzyl derivative (3) are interpreted in terms of equilibration between diastereoisomeric crown and saddle conformations in solution. The 1,9-dimethyl derivative (1) is believed to exist predominantly in the saddle conformation in solution.

Conformational behaviour of medium-sized rings. Part 9. Disalicylides and trisalicylides

Abstract: The temperature dependences of the 1H n.m.r. spectra of di-o-thymotide (13) and di-o-carvacrotide (14) have been interpreted in terms of ring inversion (12a)⇌(12b) between enantiomeric boat conformations. Comparison of the ΔG‡ values (17.7 and 18.4 kcal mol–1, respectively) for this conformational change suggests that it takes place by a pseudorotational process involving folded boat conformations (17) in which the substituents (methyl and isopropyl, respectively) on C-3 enter into 1,5-interactions with the carbonyl oxygen atoms in the eight-membered rings at the rate-determining transition states. The temperature dependences of the 1H n.m.r. spectra of tri-o-cresotide (6) and tri-m-cresotide (7) provide further evidence that a mechanism involving pedalling of trans-ester linkages through the mean plane of the twelve-membered ring accounts for the conformational changes between enantiomeric propeller (4) and helical (5) conformations. The ΔG‡ values for interconversion and inversion processes of eight- and twelve-membered ring compounds show an informative dependence upon the steric demands of the ortho-substituents on the aromatic rings.

1,3:4,6-Di-O-benzylidene-2,5-O-3,6,9,12-tetraoxatetradecane-l,14-diyl-D-mannitol and the solution state structure of its molecular complex with the benzylammonium cation. A variable-temperature 1H n.m.r. spectroscopic investigation

Abstract: The results of variable-temperature 1H n.m.r. spectroscopic investigations, including both multiple irradiation experiments and qualitative measurements of nuclear Overhauser effects, on D-(2)-PhCH2NH3ClO4 indicate that the conformation (Ha/Hc) in which the phenyl ring in the cation is oriented over one of the 1,3-dioxan rings in D-(2) becomes increasingly preferred in CD2Cl2 solution as the temperature is lowered.

Conformational behaviour of medium-sized rings. Part 13. 5,18-Dihydro- and 5,11,12,18-tetrahydrotribenzo[b,f,j][1,4]diazacyclododecine-6,17-diones

Abstract: The unsaturated (3) and saturated (6) bislactams have been prepared from condensations of o-phenylenediamine with the bisacyl chlorides (1) and (2) derived from trans-stilbene-2,2′-dicarboxylic acid and bibenzyl-2,2′-dicarboxylic acid, respectively. Dynamic 1H n.m.r. spectroscopy demonstrates that the 5,18-dibenzyl derivative (5) of (3) and the 5,18-dimethyl-(7) and 5,18-dibenzyl-(8) derivatives of (6) adopt enantiomeric non-planar conformations with averaged C2 symmetry in solution. In the case of the two 5,18-dibenzyl derivatives (5) and (8), ring inversion is shown to be slow (ΔG‡= 20.4 and 21.1 kcal mol–1, respectively) on the 1H n.m.r. time scale at room temperature and probably involves propeller-like conformations (9a)⇌(9b) as the enantiomeric groundstate conformations. Both the 5,18-dimethyl-(7) and -dibenzyl (8) derivatives of the saturated bislactam (6) form 1 : 1 inclusion compounds, (7) with o-xylene and (8) with ethanol.

A comparison between the solid state structures and solution behaviour of molecular complexes formed between primary alkylammonium salts and chiral crown ethers incorporating 1,2:4,6-diacetals of D-mannitol

Abstract: The results of an X-ray crystallographic study of D-(1)-Me2CHNH3ClO4 and D-(2)-PhCH2NH3CIO4 reveal conformational features and a hydrogen bonding pattern in the 1:1 complexes which may be correlated with the complexaton behaviour of the 20-crown-6 derivatives D-(1), D-(2), and (3) in solution towards a range of cationic guest species.