Synthesis of a new class of homochiral amines and novel bio-active tropanes

This thesis describes two main programmes: the synthesis of a new class of homochiral amines and the synthesis of ketone analogues of 3a-esterified tropane alkaloids. In chapter one, a scaled-up synthesis of (5)-a-(diphenylmethyl)pyrrolidine 1 is described. The key hydrogenation step of the oxazolidinone intermediate 2 was extended to the synthesis of the other chiral amines 70, 73, 76, 79 and 82. Hydrogenation of the oxazolidinones proceeded in good yields (71 - 87 %) and was not susceptible to racemisation. Thus, a convenient route from amino acid ester hydrochlorides (S)-valine 65, (S)-phenylalanine 66, (S)-alanine 67, (S)-isoleucine 68 and (S)-leucine 69 allowed a range of novel chiral amines to be prepared. In chapters two and three, a new route to ketone analogues of tropane esters is described. In chapter two, results of an attempt to prepare ketone 110 are outlined. Ketone 110 is an analogue of the tropane alkaloid littorine 101, where the bridging ester O atom is replaced by a CH2 group. The first approach to ketone 110 involved the Wittig reaction of acetylmethylenephosphorane 118 and the Homer-Wadsworth- Emmons reaction of diethylbenzoylmethanephosphonate 122 with tropinone 116. Tropinone 116 was found to be particularly unreactive in both cases. The second approach to ketone 110 involved the coupling reactions of both N-troc-3a- tosyloxymethyltropane 170 and N-troc-3 a-iodomethyltropane 185 with 2-phenylacetyl- 1,3-dithiane 147 and 1,3-ditihiane 142. These were also unreactive and as a result the synthesis of ketone 110 remains unresolved. In chapter three, the synthesis of other ketone analogues of naturally occurring 3 a- esterified tropane alkaloids is described. A six-step route to the ketones was devised and in this route the Grignard reactions of tropan-3 -ylacetaldehyde 227 emerged as the key to the success of the strategy. Three ketone analogues 218, 219 and 220 of tropate esters were successfully prepared. Ketone 220, the analogue of apoatropine 201, was found to be a muscarinic acetylcholine receptor antagonist (EC(_50) 1.9x10(^-7) M) in guinea-pigileum, showing a 500-fold less activity than atropine 202. However the activity is still within the clinical range

Some applications and chemistry of (S)-2-(diphenylmethyl)-pyrrolidine

The synthetic utility of (S)-2-(diphenylmethyl)-pyrrolidine (1) and its amide derivative, (S)-2-(diphenylmethyl)-5-oxo-pyrrolidine (2) were examined in two contexts; as chiral auxiliary compounds in asymmetric alkylation reactions and Diels- Alder reactions; as chiral solvating agents (CSAs) for (^1)NMR evaluation of chiral acids and alcohols. In the former case, it was shown that monoalkylation of N-acyl derivatives of (1) and (2) using lithiated bases led to poor diastereoselectivities (1:1 to 1.12:1) and poor yields (28 to 33 %), while alkylation reactions using HMPA proceeded with modest diastereoselectivities (1.49:1 to 4.25:1). The results of the Diels-Alder study remain premature at present. In the latter case, (1) was an excellent chiral solvating agent (CSA) for chiral carboxylic acids, however it was less effective for chiral alcohols. The amide derivative (2) was substantially less effective as a CSA for chiral carboxylic acids and failed completely to resolve chiral alcohols

Synthesis of novel multifunctional carbazole-based molecules and their thermal, electrochemical and optical properties

Two novel carbazole-based compounds 7a and 7b were synthesised as potential candidates for application in organic electronics. The materials were fully characterised by NMR spectroscopy, mass spectrometry, FTIR, thermogravimetric analysis, differential scanning calorimetry, cyclic voltammetry, and absorption and emission spectroscopy. Compounds 7a and 7b, both of which were amorphous solids, were stable up to 291 °C and 307 °C, respectively. Compounds 7a and 7b show three distinctive absorption bands: high and mid energy bands due to locally excited (LE) transitions and low energy bands due to intramolecular charge transfer (ICT) transitions. In dichloromethane solutions compounds 7a and 7b gave emission maxima at 561 nm and 482 nm with quantum efficiencies of 5.4% and 97.4% ± 10%, respectively. At positive potential, compounds 7a and 7b gave two different oxidation peaks, respectively: quasi-reversible at 0.55 V and 0.71 V, and reversible at 0.84 V and 0.99 V. At negative potentials, compounds 7a and 7b only exhibited an irreversible reduction peak at −1.86 V and −1.93 V, respectively

Carbazole-based D-π-A molecules: determining the photophysical properties and comparing ICT effects of π-spacer and acceptor groups

4-(9′-Hexylcarbazol-3′-yl)benzaldehyde (Cz-Ph-CHO: 4) and 4-(9′-hexylcarbazol-3′-yl)benzylidenemalononitrile (Cz-Ph-CN: 5) were synthesised with the structure of D-π-A, where carbazole, phenylene and formyl/dicyanovinyl groups act as electron donor (D), pi-spacer (π) and electron acceptor (A) units, respectively. The thermal, electrochemical, optical and intramolecular charge transfer (ICT) properties of compounds 4 and 5 were investigated. Compounds 4 and 5, in particular their ICT behaviour, were also compared with the closely related structure, 2-(9′-hexylcarbazol-3′-yl)-5-pyridinecarbaldehyde (Cz-Py-CHO: 7). For the purpose of tuning chemical structure to obtain targeted properties, electrochemical data and absorption and emission measurements suggest that the dicyanovinyl unit in compound 5 is a better acceptor than formyl in compound 4, and that pyridine in compound 7 is a better π-spacer than benzene in compound 4, in exerting ICT characteristics such as fluorosolvatochromism and Stokes shifts

Yellowish-orange and red emitting quinoline-based iridium(III) complexes: synthesis, thermal, optical and electrochemical properties and OLED application

Two novel heteroleptic iridium(III) acetylacetonate (acac) complexes K3a and K3b were synthesised from cyclometallating ligands of 2-(4′-formylphenyl)quinoline 11a and 2-(5′-formylphenyl)quinoline 11b. Complexes K3a and K3b were fully characterised by NMR spectroscopy, mass spectrometry and FT-IR. Differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA) indicate that both complexes were amorphous solids, stable up to 303 °C and 313 °C, respectively. Complexes K3a and K3b showed strong, high-energy absorption bands (<400 nm) due to ligand-centred (1LC) transitions and weaker, low-energy absorption bands (400−600 nm) arising from a mixture of metal-to-ligand charge transfer (1MLCT/3MLCT) and ligand-centred (3LC) transitions. In degassed dichloromethane solutions, complexes K3a and K3b gave yellowish-orange and red phosphorescent emissions at 579 nm and 630 nm, with quantum efficiencies of 99.3 % and 79.3 %, respectively. At positive potential, complexes K3a and K3b exhibited a one-electron reversible oxidation (Eox1/2) peak at 0.69 V and a quasi-reversible oxidation (Eox1/2) peak at 0.60 V, respectively, which were assigned to the Ir(III)/Ir(IV) couple. At negative potentials, complexes K3a and K3b exhibited a one-electron irreversible reduction peak at -1.79 V and -1.94 V, respectively. Phosphorescent organic light-emitting diodes (PhOLEDs) were fabricated with a device configuration of ITO/PEDOT:PSS/EML/TPBi/LiF/Al, in which K3a and K3b gave yellowish-orange and red electroluminescence (EL) at 572 nm and 628 nm, respectively. Complex K3a gave the highest luminance of 2773 cd/m2, current efficiency of 3.3 cd/A, external quantum efficiency of 1.2 % and maximum power efficiency of 1.05 lm/W with a turn-on voltage of 5.0 V (Device A)

Carbazole-based D-π-A molecules: Determining the photophysical properties and comparing ICT effects of π-spacer and acceptor groups

4-(9′-Hexylcarbazol-3′-yl)benzaldehyde (Cz-Ph-CHO: 4) and 4-(9′-hexylcarbazol-3′-yl)benzylidenemalononitrile (Cz-Ph-CN: 5) were synthesised with the structure of D-π-A, where carbazole, phenylene and formyl/dicyanovinyl groups act as electron donor (D), pi-spacer (π) and electron acceptor (A) units, respectively. The thermal, electrochemical, optical and intramolecular charge transfer (ICT) properties of compounds 4 and 5 were investigated. Compounds 4 and 5, in particular their ICT behaviour, were also compared with the closely related structure, 2-(9′-hexylcarbazol-3′-yl)-5-pyridinecarbaldehyde (Cz-Py-CHO: 7). For the purpose of tuning chemical structure to obtain targeted properties, electrochemical data and absorption and emission measurements suggest that the dicyanovinyl unit in compound 5 is a better acceptor than formyl in compound 4, and that pyridine in compound 7 is a better π-spacer than benzene in compound 4, in exerting ICT characteristics such as fluorosolvatochromism and Stokes shifts. © 2021 Elsevier B.V

A red-orange carbazole-based iridium(III) complex: Synthesis, thermal, optical and electrochemical properties and OLED application

A novel heteroleptic iridium(III) acetylacetonate (acac) complex, (L-5-CHO)2Ir(acac) (3b), was synthesised from 2-(9’-hexylcarbazole-3’-yl)-5-formylpyridine (L-5-CHO) (1b). The complex 3b was determined to be thermally and electrochemically stable. The photoluminescence properties of the compound were studied, with a dichloromethane solution of 3b giving structureless emission at 662 nm, showing that the formyl group red-shifted the emission by 151 nm compared to the parent complex. Complex 3b was also shown to possess a moderate photoluminescence quantum yield (67%) and a short emission lifetime (τ = 280 ns). Organic light-emitting diodes (OLEDs) were fabricated with a solution-processed emissive layer (EML) consisting of poly(N-vinylcarbazole) (PVK), 2-(4-tert-butylphenyl)-5-(4-biphenylyl)-1,3,4-oxadiazole (PBD) and iridium complex (3b). The OLEDs containing complex 3b showed red-orange electroluminescence (EL) at 624 nm. The influence of the host materials was studied and the best performance was achieved with both PVK and PBD in the emissive layer, with the resulting OLEDs exhibiting a current efficiency of 0.84 cd/A, a power efficiency of 0.20 lm/W, and an external quantum efficiency (EQE) of 0.66% at a brightness of 2548 cd/m2

Colour tuning from green to red by substituent effects in phosphorescent tris-cyclometalated iridium(III) complexes of carbazole-based ligands: synthetic, photophysical, computational and high efficiency OLED studies

Two series of fac-tris-cyclometalated iridium(III) complexes, series 1 from the 2-(carbazol-3'-yl)-pyridine ligands, and series 2 from the isomeric 2-(carbazol-2'-yl)-pyridine ligands, have been characterised. The photoluminescence and electroluminescence from series 2 complexes are red shifted compared to series 1 complexes, due to the increased electron donating ability of the carbazole unit in series 2. The attachment of trifluoromethyl and methoxy substituents to the pyridyl ring in these complexes results in colour tuning of phosphorescence energy maxima over the range 494-637 nm (green to red). These complexes possess predominantly (MLCT)-M-3 (metal-to-ligand-charge transfer) excited states. DFT/TD-DFT computations correctly predict the phosphorescence emission maxima and show that the HOMOs in these complexes contain mixed iridium and carbazolyl character. The carbazolyl ligand contributions to the excited states increase in series 2 compared to series 1. Complexes of series 1 exhibit high phosphorescence quantum yields whereas complexes of series 2 show lower quantum yields. Solution processed organic light emitting devices (OLEDs) with series 1 complexes using the high triplet poly(9-vinylcarbazole) (PVK) as the host polymer exhibit very high performances of up to 40 cd A(-1) and external quantum efficiency of 12%. For series 2 the highest current efficiency is 10.3 cd A(-1) and external quantum efficiency of 5.6%.UK Research & Innovation (UKRI)Engineering & Physical Sciences Research Council (EPSRC) - EP/I013695/

Molecular Bridging of Silicon Nanogaps

The highly doped electrodes of a vertical silicon nanogap device have been bridged by a 5.85 nm long molecular wire, which was synthesized in situ by grafting 4-ethynylbenzaldehyde via C-Si links to the top and bottom electrodes and thereafter by coupling an amino-terminated fluorene unit to the aldehyde groups of the activated electrode surfaces. The number of bridging molecules is constrained by relying on surface roughness to match the 5.85 nm length with an electrode gap that is nominally 1 nm wider and may be controlled by varying the reaction time: the device current increases from <= 1 pA at 1 V following the initial grafting step to 10-100 nA at 1 V when reacted for 5-15 min with the amino-terminated linker and 10 mu A when reacted for 16-53 h. It is the first time that both ends of a molecular wire have been directly grafted to silicon electrodes, and these molecule-Induced changes are reversible. The bridges detach when the device Is rinsed with dilute add solution, which breaks the imine links of the in situ formed wire and causes the current to revert to the subpicoampere leakage value of the 4-ethynylbenzaldehyde-grafted nanogap structure