From Cyclic Thioureas

The homocyclic carbodiimides 16 were first synthesized by Behringer and Meier in 1957 by dehydrosulfurization of cyclic thioureas 15 with HgO. 

Macrocyclic bis-thioureas 17, on treatment with PhsP and CCU/EtsN, afford cyclic bis-carbodiimides 18. ° 

The cyclic thiourea 19, upon reaction with HgO affords the cyclic carbodiimide 20, but the compound has not been isolated in pure form.  

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Hyperthyroidism may be treated in several ways. One of these is interference with the synthesis of the thyroid hormones, possibly by removal of iodine. Thiourea and cyclic thioureas have this effect and of such cyclic compounds, thiouracil (1030 R = H), its 6-alkyl derivatives (1030 R = Me or Pr) and thiobarbital (1031) are effective thyroid drugs. Today only propylthiouracil (1030 R = Pr) is widely used, probably because it has fewer side effects than the others (71MI21302). The thiouracils are made by the Principal Synthesis from a /3-oxo ester (1032 R = H, Me, Pr, etc.) and thiourea (45JA2197) their fine structures are experimentally based (64AF1004). 

Cyclic thiourea derivatives having three different types of cyclophane structure (ortho-meta, meta-meta and meta-para) and a lariat-type thiourea have been synthesized, using reaction of isothiocyanate with amine.230 Cyclic thioureas have been obtained from formaldehyde aminals and sulfur (Sg) (Scheme 77).231... 

The direct reaction of [TCO4] in ethanolic solution with dppe and oxalic acid produces the red Tc" complex [Tc(ox)(dppe)2] (552). Attempts to prepare similar complexes with succinic acid, phthalic acid, or salicylic acid failed, or the complexes were stable in solution only. " Similarly, cationic complexes of Tc" are produced by reaction of the versatile precursor [TcO(OH)(dppe)2] (204) with various dithiocarbamates, which produces several complexes of general formula [Tc(dtc)(dppe)2] (553). For this reaction the reductant formamidine sulphinic acid (510) was required in an alkaline solution. The X-ray crystal structure of [Tc(S2CNMe2)(dppe)2] (554) shows a distorted octahedral geometry. Cyclic voltammetry reveals a reversible reduction wave Tc"/Tc couple at —0.53 V, and a reversible oxidation at +0.3 V for the Tc" /Tc" couple. The same compound (554) was also prepared from the thiourea precursor [TcO(tmtu)4] + (91).The reaction of this precursor in dmf in the presence of dppe produced a mixture of brown [TcO(dtc)(tmtu)2] and the Tc" complex (553). The first compound is probably an intermediate... 

An efficient, practical solid-phase synthesis of a variety of bis-hetero-cyclic compounds was developed starting from resin-bound orthogonally protected lysine (Fig. 10). Tetraamines 36 were synthesized by exhaustive reduction of resin-bound tetraamides 35. Cyclization with different commercially available bifunctional reagents such as cyanogen bromide, thio-carbonyldiimidazole, carbonyldiimidazole, and oxalyldiimidazole yielded the corresponding bis-heterocyclic compounds bis-cyclic guanidines 37,39 bis-cyclic thioureas 38, bis-cyclic ureas 39, and bis-diketopiperazines 40, respectively.40 Reduction of compounds 40 led to bis-piperazines 41. 

Fig. 11. Solid-phase synthesis of bis-cyclic thioureas and bis-cychc guanidines from resin-bound reduced tripeptides.

Antimony was also extracted as the complex with cupferron [12] or BPHA [13]. Sb(III) and As(in) can be extracted with bis(2-ethylhexyl)dithiophosphoric acid (0.1 M) in heptane from 2-4 M HCl in the presence of iodide. Only Sb(III) is re-extracted with 12 M HCl [14]. The reagent has been applied for isolation of Sb in partition chromatography [15]. Also diethyldithiophosphoric acid has been recommended for the separation of Sb(III) and As(III) [16]. In the presence of Bi and Sn, antimony was determined after extraction (CHCI3) with cyclic thiourea derivatives [17]. Sb(III) was also extracted with the use of the crown ether 18-crown-6 [18]. 

Closely related to the just-discussed transformation of sugar thiolactams into amidines is the preparation392 of the cyclic guanidinium glycomimetics 241 and 242 from the cyclic thiourea precursor 239. Replacement of the... 

The second amine group in the product from an aliphatic diamine can form salts, and the betaine that forms the primary product cyclizes when heated in hydrochloric acid, forming cyclic thiourea derivatives in good yields 91 92... 

Figure 15 Synthesis of positional scanning heterocyclic libraries (diethyltriamines 24, cyclic ureas 25, and cyclic thioureas 26) derived from dipeptides.

Many biologically active compounds contain cyclic ureas, including inhibitors of human immunodeficiency virus (HIV) protease and HIV replication [70]. Kim et al. [71] presented an illustration of the synthesis of oligomeric cyclic ureas as nonnatural biopolymers. Applying the libraries from libraries [72] concept, triamines [65] such as those described earlier were used as templates for the generation of different heterocyclic compounds such as cyclic ureas, cyclic thioureas, and bicyclic guanidines [65]. The cyclizations to obtain the five-membered ring cyclic ureas and cyclic thioureas were... 

Systems Containing Four Heteroatoms 1,3,4,6-Thiatriazepines were obtained from reaction of 1,4-dichloro-2,3-diazabutadienes with cyclic thioureas (Scheme 31). 

Alkylation of the cyclic thiourea with phenacyl chloride followed by treatment with isothiocyanate also yields the product (76) and other symmetrical A-alkyl derivatives in a convenient one-pot reaction <88BCJ2419>. Unsymmetrical tetraazapentalene derivatives can be prepared from the periodate oxidation products of their symmetrical analogues as described in the following section. 

This review tries to shed light on the early history of different methods for the generation of N-heterocyclic carbenes (NHCs), i.e., the extrusion of heterocumulenes (decarboxylations) from suitable mesomeric betaines, deprotonations of hetarenium salts, a-eliminations, tautomerizations of mesomeric betaines, and reductive desulfurizations of cyclic thioureas. Selected examples of acyclic and three- to eight-membered NHCs are presented, as well the generation of selected five- and six-membered anionic NHCs. 

Finally, a few references have appeared in which bidentate compounds have been cyclized using well understood chemistry to produce some novel heterocycles. There are numerous examples of 5- and 6-membered diazaphos-phorus heterocycles but there are far fewer with smaller or larger rings. Dichlorophosphinyl carbamates, prepared from isocyanates, have been cyclized with diamines to afford the novel benzodiazaphosphepin system (395). Oxadiazepins (396) have been prepared by reaction of the amino-oximes with formaldehyde and 1,3,4,6-thiatriazepins (397) were obtained by Moss and Taylor using cyclic thioureas. 

Treatment of cyclic carbonates of 1,2-diols with thiocyanate ion at temperatures of 100 °C or higher yields thiiranes (Scheme 145) (66CRV297, 75RCR138). Thiourea cannot replace thiocyanate satisfactorily, and yields decrease as the carbonate becomes more sterically hindered. The reaction mechanism is similar to the reaction of oxiranes with thiocyanate (Scheme 139). As Scheme 145 shows, chiral thiiranes can be derived from chiral 1,2-diols (77T999, 75MI50600). 

Experiments with cyclic thioethers (80JCS(P1)1693), thiourea, thiocyanate and ethyl xan-thate always led to destruction of oxaziridines (73AJC2159). Products of complicated consecutive reactions could be isolated but only with some difficulty, e.g. (92) from a reaction with carbon disulfide (74JOC957), and (93), obtained by trapping with butadiene a product of a reaction between an oxaziridine and a thiirane (80JOC1691). 

Symmetrical dialkyl and diaryl thioureas have been prepared in generally good yield (60-90%) from the reaction of the amine with thiophosgene, formed in situ from the catalysed reaction of carbon tetrachloride with sodium sulphide [5], Reaction with diamines yields cyclic ureas. 

The oxidation step of thioureas can be reversed, as was shown by cyclic voltammetry to regenerate thiourea from anodically produced dimeric salt (in AN/BU4NCIO4, potentials vs Ag/Ag+) (Scheme 1). 

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