The controlled release of reactive diatomic molecules from peri- and peri-like substituted disulfides

Prior, Connor ORCID: 0000-0001-7898-8408 (2022). The controlled release of reactive diatomic molecules from peri- and peri-like substituted disulfides. University of Birmingham. Ph.D.

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Abstract

Sulfur monoxide has been known for a little over a century. SO has been known to have 3 electronic configurations in which it exists – two of which have been used in organic synthesis. In the last 70 years it has become a useful reagent in organic synthesis displaying a wide range of reactivities with many different functionalities. That being said, only 2 reports confirm singlet SO has been released and captured. These two papers display a large scope of the reactivity of singlet SO but neither display excellent yields that are reported for triplet SO release and capture. The most efficient triplet SO transfer reagent was report by Grainger et al. in 2001 and 2011. This involved the release from peri-substituted trisulfide-2-oxides and capture using a variety of dienes. Therefore, there is still scope for an efficient singlet SO transfer reagent which displays capture of singlet SO.

This thesis reports the synthesis, study and controlled release of SO from 4 novel trisulfide-2- oxides (\(\textbf{299}\), \(\textbf{300}\), \(\textbf{301}\), and \(\textbf{302}\)). All of the trisulfide-2-oxides were synthesised from the corresponding disulfides (\(\textbf{266}\), \(\textbf{264}\), \(\textbf{295}\), and \(\textbf{298}\)) via the reduction of the disulfide (or disulfide/trisulfide mixtures) to the dithiol in yields comparable to previously reported trisulfide-2-oxides (45 – 50 % yield). The dithiol is subject to either SOCl\(_2\)/pyridine or SO(im)\(_2\). SO(im)\(_2\) shows a novel method to synthesise trisulfide-2-oxides. All novel trisulfide-2-oxides were crystallised, and the crystallographic data has been compared. The crystallographic data explains how strain within a system can alter the release rate of SO from a trisulfde-2-oxide.

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\(\textbf{Figure 1}\) Top row - proposed disulfides (naphthalene \(\textbf{107}\), acenaphthene \(\textbf{266}\), acenaphthylene \(\textbf{264}\), fluorene \(\textbf{298}\), and carbazole \(\textbf{295}\)) Bottom row - proposed trisulfide-2- oxides (naphthalene \(\textbf{105}\), acenaphthene \(\textbf{299}\), acenaphthylene \(\textbf{300}\), fluorene \(\textbf{301}\), and carbazole \(\textbf{302}\)).

Finally, each of the trisulfide-2-oxides have been pyrolysed in the presence of 2,3-dimethyl-1,3-butadiene in chlorobenzene at reflux. None of the novel trisulfide-2-oxides in this study perform better than the previously developed naphthalene trisulfide-2-oxide \(\textbf{105}\). Similarly, none of the trisulfide-2-oxides in this study performed as well as naphthalene trisulfide-2- oxide under photolysis conditions. However, carbazole trisulfide-2-oxide \(\textbf{302}\) has shown potential to be a singlet SO transfer reagent, with preliminary results indicating that singlet SO has reacted with cycloheptatriene to form bridged sulfoxide \(\textbf{181 (Scheme 1)}\).

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\(\textbf{Scheme 1}\) Singlet SO release from carbazole trisulfide-2-oxide \(\textbf{302}\) to yields disulfide \(\textbf{295}\) and sulfoxide \(\textbf{181}\).

Carbon monoxide and carbon monosulfide are two reactive diatomic molecules. CO has been shown to have extensive uses in organic synthesis and is an important biological signalling molecule (and has also been shown to be a therapeutic despite its potent toxicity). Carbon monosulfide has very little literature on its uses in synthesis. This could be due to the difficulty generating CS.

Naphthalene dithiocarbonate \(\textbf{336}\) and trithiocarbonate \(\textbf{375}\) have been synthesised by modified procedures from Ogura et al. These same procedures were used to the synthesise acenaphthene dithiocarbonate \(\textbf{227}\) and trithiocarbonate \(\textbf{377}\), acenaphthylene dithiocarbonate \(\textbf{228}\), 2,7-dimethoxynaphthalene trithiocarbonate \(\textbf{376}\). All the compounds have been crystallised and their diffraction data analysed, and comparisons between each system have been made. The naphthalene, acenaphthene, and acenaphthylene dithiocarbonates (\(\textbf{226}\), \(\textbf{337}\), and \(\textbf{338}\)) were subjected to irradiation from a medium pressure Hg lamp – causing photochemical degradation to the corresponding disulfide (\(\textbf{107}\), \(\textbf{266}\), and \(\textbf{264}\)).

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\(\textbf{Figure 2}\) Top row - proposed dithiocarboantes (naphthalene \(\textbf{336}\), acenaphthene \(\textbf{337}\) and, acenaphthylene \(\textbf{338}\)). Bottom row - proposed trithiocarbonates (naphthalene \(\textbf{375}\), 2,7- dimethoxy naphthalene \(\textbf{376}\) and, acenaphthene \(\textbf{377}\)).

Naphthalene trithiocarbonate was irradiated using 365nm LED strips in the following solvents; toluene, PhF, PhCl, DMF, CH\(_2\)Cl\(_2\), CHCl\(_3\), and THF. Decomposition occurred in THF, but in no others. Morpholine (10 eq) was added and the solvent screen was re-trialled. Decomposition occurred in all solvents. The reactions were repeated but 1,3,5-trimethoxybenzene was added as an NMR standard. Percentage yields of all components in the reaction have been determined via \(^1\)H NMR integration.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):