Synthesis and reactivity of succinylthioimidazolium salts: A unified strategy for the preparation of thioethers

by Marvin Jeldrik Böhm
Doctoral thesis
Date of Examination:2020-12-14
Date of issue:2020-12-21
Advisor:Prof. Dr. Manuel Alcarazo
Referee:Prof. Dr. Lutz Ackermann
Referee:Prof. Dr. Dietmar Stalke
Referee:Dr. Holm Frauendorf
Referee:Prof. Dr. Konrad Koszinowski
Referee:Prof. Dr. Johannes C. L. Walker
Persistent Address: http://dx.doi.org/10.53846/goediss-8378

 

 

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Abstract

English

Sulfur is one of the main group elements on our planet with a natural abundance of (0.46±0.15)w%. In its most common allotropic form sulfur is a yellow powder and exhibits a cyclic S8 structure. Apart of the cyclic S8 form, several smaller and larger ring allotropes of Sn with n = 6 to 20 have been isolated. Aside from its natural occurrence as the pure element, sulfur is also forming inorganic salts like sulfides, sulfates, or sulfites. Moreover, sulfur plays an important role in the field of organic chemistry and biochemistry.[2] In this regard various sulfur-containing functional groups with different oxidation states of the sulfur atom, e.g. thiols (+II), disulfides (+I), sulfoxides (+IV) and sulfones (+VI) and thioethers (+II), are known.Especially aryl thioethers are predominantly important representatives of sulfur containing functional groups in organic chemistry because of their appearance in key scaffolds of pharmaceutical important compounds, natural products, in the field of material science as well as in the field of ligand design. Additionally, aryl thioethers, also known as aryl sulfides, are a versatile synthetic platforms because they can be easily converted in a variety of other functional groups and find also applications as directing groups in chemistry of C–H functionalization. Due to the significant importance of this compound class, this work focuses on the development of a transition metal free and highly modular protocol for the synthesis of a wide range of different unsymmetrically substituted aryl thioethers. Furthermore, the developed concept is used to access further sulfur-containing compounds as (arylthio)sulfonamides. In the presented thesis, a highly modular protocol for the transition metal-free preparation of diaryl and alkyl aryl sulfides was accomplished as a significant contribution to the area of sulfide synthesis. For this purpose, imidazole-2-thione-derived sulfenylation reagents were developed. It was shown that their versatile reactivity allowed the initial activation of several unfunctionalized (hetero)arenes. Additionally, the protocol demonstrated a high functional group tolerance. Hereby, the influence of the sulfur-containing thiourea backbone as well as the effect of the electron-withdrawing N-succinimidyl moiety in the reagents was studied. In a consecutive step, metal organyls were identified as suitable nucleophiles for the synthesis of aryl sulfides from a cationic intermediate which were isolated in moderate to excellent yields. The presented reagent can be considered as a synthetic equivalent of a [S]2+ synthon which undergoes a double electrophilic attack. Noteworthy, the herein developed protocols allow the sequential twofold sulfenylation of electron-rich heterocycles like N-phenylpyrrole. In addition, several cationic intermediates were crystallized and analyzed by X-ray crystallography to verify their molecular connectivity. The general methodology was further extended toward the synthesis of unsymmetrical aryl selenides. Based on these results, an efficient single step protocol for the synthesis of imidazolyl and further heterocyclic thioethers was elaborated. With this, further diheteroaryl sulfides were synthesized in yields of up to 82% from the in situ formed reagents.
Keywords: transition metal free; arylsulfide; organic chemistry; electrophilic sulfenylation; mechanistical studies; imidazolthioether; late-stage-functionalization
 
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