Exploring the Conversion of Macrocyclic 2,2′-Biaryl Bis(thioureas) into Cyclic Monothioureas: An Experimental and Computational Investigation

Abstract

Macrocyclic bis­(thioureas) derived from 2,2′-biphenyl and binaphthyl skeletons have been synthesized by reaction of 2,2′-diaminobiaryl and 2,2′-bis­(isothiocyanato)­biaryl derivatives. The splitting of these bis­(thioureas) into two units of the respective cyclic monothioureas has been monitored by NMR, shedding some light on the factors that control these processes. Additionally, a computational study revealed up to three mechanistic paths for the conversion of the 2,2′-biphenyl-derived bis­(thiourea) into the corresponding monothiourea. The proposed mechanisms account for the participation of a molecule of water as an efficient proton-switch as well as for different classes of putative intermediates. The computational study also supports the ability of the thiourea group to participate in a plethora of processes, such as prototropic equilibria, sigmatropic shifts, heteroene and retro-heteroene reactions, and cis ⇆ trans isomerizations.

2,2′‐Bis(arylamino)‐1,1′‐biaryls as Building Blocks for the Synthesis of Dibenzo[d,f][1,3]diazepines, Dibenzo[d,f][1,3]diazepinones, and Dibenzo[c,e][1,2,7]thiadiazepine 6‐Oxides

“…We then focused on the synthesis of sulfur‐containing seven‐membered ring systems. Although, 5,7‐dihydrodibenzo[ d , f ][1,3]diazepine‐6‐thiones [11,22,23] and 5,7‐dihydrodibenzo[ c , e ][1,2,7]thiadiazepine 6,6‐dioxides [36] have been described, there is no report for the synthesis of 5,7‐dihydrodibenzo[ c , e ][1,2,7]thiadiazepine 6‐oxides. In analogy to the method described above for the synthesis of the dibenzo[ d , f ][1,3]diazepinones, we used diphenyl sulfite as 1,1‐dielectrophile.…”

“…Although already described in 1929 by Le Fèvre, [11] only limited reports for the construction of 1,3‐diazepines are known. Despite considerable recent synthetic efforts in this area, [1d,3a,b,d,12–26] the synthesis of functionalized 1,3‐diazepine derivatives remains a challenging task. Therefore, better synthetic routes to the 1,3‐diazepine framework from readily available starting materials are desirable.…”

Synthesis of Dibenzo[d,f][1,3]Diazepines via Elemental Sulfur-Mediated Cyclocondensation of 2,2′-Biphenyldiamines with 2-Chloroacetic Acid Derivatives

“…Benzodiazepines are important structural units found in a variety of biologically active agents, including natural products (e.g., streptocarbazoles A and B) and major drugs (e.g., anxiolytics, such as cloxazolam, ketazolam, flumazenil, clobazam, delorazepam, alprazolam, etc., the anesthetic midazolam, the tranquillizer ethyl loflazepate) . The prevalence of the dibenzo­[ d , f ]­[1,3]­diazepine motif in medicinally relevant compounds, dyes, catalysts, , MOFs (metal–organic frameworks), , and organic electronics materials (Figure ) has inspired the development of many novel methods for their preparation. − Thus, iodine-mediated coupling of 2,2′-diaminobiphenyl with aldehydes, cyclocondensation of silylamines with CO 2 , the reaction of 2,2′-diaminobiphenyl with bis­(isothiocyanate), the titanacarborane monoamide-catalyzed reaction of diamines with carbodiimides, cyclization reactions of 3-methyleneoxindoles with 2-cyano-2-(3,4-dihydronaphthalen-1­(2 H )-ylidene)­acetate, and indolin-2-ones with 4-methylthio-2 H -pyran-2-one-3-carbonitriles , have been recently reported. However, there is a limited number of protocols for assembling 2-carboxy-substituted dibenzo­[1,3]­diazepine derivatives that hold promise for materials science and medicinal chemistry.…”