Selective synthesis of multicomponent crystals using mechanochemistry and sublimation

Lombard, Jean (2020-12)

Thesis (PhD)--Stellenbosch, 2020.

Thesis

ENGLISH ABSTRACT: The aim of this thesis is to demonstrate how careful control of the crystallisation technique used can lead to selective multicomponent crystal formation. Multicomponent materials are often crystallised from solution; however, with this study we were interested in exploring less conventional solid-state and gas-phase methods, such as mechanochemistry and sublimation. In the first study investigations of two systems are reported: succinic acid with hexamethylene-tetramine, and oxalic acid with 4,4'-bipyridine. Each of these sets of molecules forms both salts and co-crystals. The majority of these multicomponent forms have previously been crystallised from solution, and in this study it was found that they can also be formed mechanochemically, and from the gas phase. The formation of molecular salts by co-sublimation of neutral components was unexpected and has not been reported before. Once formed, these multicomponent crystals could also be re-sublimed so that mixtures of different crystal forms could physically be separated. This work raises important questions about the processes occurring in the gas phase during sublimation – preliminary experiments indicate that ions (or rather clusters of ions) may be present in the gas phase during the sublimation of these salts.The second study aimed to determine the effect of solvent type and volume on the selectivity between hydrogen- and halogen-bonded co-crystals. A competition study was carried out between four analogous co-crystals containing a ditopic acceptor molecule, 1,2-bis(4-pyridyl)ethane, and either a hydrogen-bond or halogen-bond donor molecule. A number of different crystallisation methods were used, including sonic slurry crystallisation, neat grinding, liquid-assisted grinding, and co-sublimation. We observed a preference for the halogen-bonded co-crystal when polar solvents were used (which was also previously observed), but this selectivity became much less pronounced as the amount of solvent was reduced. Competition experiments carried out by vacuum sublimation exclude all solvent, and it was found that all selectivity for one form over another was eliminated in sublimation co-crystallisation. The amount of solvent used, and not just its polarity, is therefore critical when co-crystallisation is attempted.The third study describes the formation of a range of multicomponent crystals using mechanochemistry and sublimation, in order to compare these two crystallisation methods and determine the general capability and versatility of co-sublimation. Co-crystals, salts, and their polymorphs are discussed, as well as problems that can arise due to sublimation temperature differences, isomerisation, and degradation. Co-sublimation is shown to be a valuable co-crystallisation technique for the discovery and identification of new multicomponent materials. In its entirety this thesis demonstrates the important effect that crystallisation technique has on multicomponent crystal formation. In our opinion, a multi-technique approach which includes solid-state and gas-phase techniques is the best course of action when working with complex or problematic systems.

AFRIKAANSE OPSOMMING: Die doel van hierdie tesis is om te demonstreer hoe noukeurige beheer oor die kristallisasie tegniek wat gebruik word kan lei tot die selektiewe vorming van multikomponent kristalle. Multikomponent materiale word gereeld gekristaliseer vanuit oplossing, maar met hierdie studie het ons daarin belang gestel om minder konvensionele vastestoffase en gasfase metodes, soos meganochemie en sublimasie, te ondersoek. In die eerste studie word twee sisteme gerapporteer: butanoësuur met heksametieleentetramien, en oksaalsuur met 4,4'-bipiridien. Elkeen van hierdie stelle molekules vorm beide soute en ko-kristalle. Die meerderheid van hierdie multikomponent vorms is voorheen gekristalliseer vanuit oplossing, en in hierdie studie is daar gevind dat hulle ook meganochemies en vanuit die gas fase gevorm kan word. Die vorming van molekulêre soute deur die ko-sublimasie van neutrale komponente was onverwags en is nog nie voorheen gerapporteer nie. As die multikomponent kristalle eers gevorm is, kon hulle ook hersublimeer sodat mengsels van verskillende kristalvorms fisies geskei kon word. Hierdie werk stel belangrike vrae bloot omtrent die prosesse wat plaasvind in die gas fase gedurende sublimasie – voorlopige eksperimente dui aan dat ione (of eerder ioon bondels) dalk in die gas fase voorkom tydens die sublimasie van hierdie soute. Die tweede studie beoog om te bepaal wat die effek van die tipe en volume oplosmiddel is op die selektiwiteit tussen waterstof- en halogeen-gebinde ko-kristalle. ʼn Studie aangaande hierdie kompetisie is uitgevoer tussen vier analoë ko-kristalle wat elk ʼn ditopiese akseptor molekule, 1,2-bis(4-piridiel)etaan, bevat asook ʼn waterstof-bindende of halogeen-bindende donor molekule. ʼn Aantal verskillende kristallisasie metodes is gebruik, insluitende soniese kristallisasie, droë- en vloeistof-vergemaklikde meganochemie en ko-sublimasie. Ons het ʼn voorkeer vir halogeen bindings waargeneem wanneer polêre oplosmiddels gebruik word (wat reeds voorheen rapporteer is), maar gevind dat hierdie selektiwiteit veel minder opmerkend is wanneer die hoeveelheid oplosmiddel verminder word. Kompetisie eksperimente wat uitgevoer is deur vakuum sublimasie sluit alle oplosmiddel uit, en daar is gevind dat alle selektiwiteit vir een vorm bo ʼn ander dus geëlimineer word gedurende ko-sublimasie. Die hoeveelheid oplosmiddel wat gebruik word, en nie net die polariteit nie, is dus belangrik wanneer ko-kristallisasie uitgevoer word.Die derde studie beskryf die vorming van ʼn reeks multikomponent kristalle deur gebruik te maak van meganochemie en sublimasie sodat hierdie twee kristallisasiemetodes vergelyk kan word, sodat die algemene bruikbaarheid en veelsydigheid van ko-sublimasie bepaal kan word. Ko-kristalle, soute, en hul polimorfs word bespreek, sowel as probleme wat kan ontstaan na aanleiding van verskille in sublimasie temperature, isomerisasie, en degradasie. Ko-sublimasie is tentoongestel as ʼn nuttige ko-kristallisasie tegniek vir die ontdekking en identifikasie van nuwe multikomponent materiale. As ʼn geheel demonstreer hierdie tesis die belangrike effek wat kristallisasie tegniek op multikomponent kristal formasie het. In ons opinie is ʼn benadering wat ʼn verskeidenheid tegnieke insluit (beide vastestoffase en gasfase tegnieke) die beste plan van aksie wanneer daar met komplekse en problematiese sisteme gewerk word.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/109136
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