Thiourea functionalities

The catalysts bearing a cyclohexylamine moiety combined with a bulky sal-icylidene compound linked via one thiourea function to a terf-leucine ben-zylamide (Scheme 38, Ri = Bn, R2 = H) was the most efficient. The test was performed in solution at - 78 °C, with HCN as the cyanide source. Excellent results were obtained 78% isolated yield with 91% ee for the optimised substrate and 70-86% ee for other imine derivatives (65-92% isolated yield) [148,152-157]. 

Both the ureas and thioureas are highly suitable organocatalysts for the asymmetric Strecker synthesis. For example, the thiourea function was replaced by an urea function (note the opposite configurations). The organocatalysts thus obtained showed similar activity and slightly higher enantioselec-tivities with N-allyl benzaldimine (Scheme 39,74% yield with 95% ee for Ri = Bn and R2 = H). Once again, better enantioselectivity (up to 99% ee) was at-... 

When thioxo (or thiol) derivatives (as part of a thiourea function incorporated into the heterocyclic system) are present, effective. Y-alkylation is observed. Thus, the 3-heteroaryl-substituted [l,2,4]triazolo[3,4-/)][l,3,4]thiadiazole-6(5//)-thiones 37 dissolved in sodium hydroxide solution react with alkyl halides to afford the corresponding 6-alkylthio derivatives 38 (Equation 4) <1992IJB167>. The mesoionic compounds 39, inner salts of anhydro-7-aryl-l-methyl-3-methylthio-6-sulfonyl-[l,2,4]triazolo[4,3-A [l,2,4]triazolium hydroxides, are methylated with methyl iodide to give the corresponding quaternary salts 40 (Equation 5) <1984TL5427, 1986T2121>. 

The Chen group early in 2005 constituted the novel class of thiourea-function-ahzed cinchona alkaloids with the first reported synthesis and application of thioureas 116 (8R, 9S) and 117 (8R, 9R) prepared from cinchonidine and cinchonine in over 60% yield, respectively (Scheme 6.112) [273]. In the Michael addition of thiophenol to an a,(5-unsaturated imide, the thioureas 116 and 117 displayed only poor stereoinduction (at rt 116 7% ee 117 17% ee), but high catalytic activity (99% yield/2h) (Scheme 6.112). 

Scheme 6.146 Representative adducts obtained from the asymmetric Henry reaction between nitromethane and (hetero)aromatic aldehydes under bifunctional catalysis of C6 -thiourea-functionalized cinchona alkaloid 131.

In this study, two Deloxan Metal Scavengers were investigated. The first, THP II, is a thiourea functionalized polysiloxane while the second, MP, is mercapto functionalized. Both resins have been tested in solutions containing 20 - 100 ppm Pd(II), Pd(0) or Ru(II). In addition to different metals and oxidation states, the effects of solvent (polar vs. nonpolar), temperature (25 - 80 °C) and mode (fixed bed vs. batch) were explored. These resins were found to reduce precious metal concentrations in process solutions to levels at or below the target concentration of 5 ppm, even at room temperature in the case of Pd(II) and Pd(0). The results of this study will be discussed. 

Several methods of metal removal from process solutions exist. Some of these approaches include crystallization, distillation and extraction. However, these methods can be very time-consuming and often result in loss of some valuable product. To overcome these shortcomings, Degussa has developed Deloxan Metal Scavengers as an attractive option to solve problems associated with transition metal contamination of process solutions. [3, 4, 5] Two resins are commercially available. Deloxan THP 11 (1) is a thiourea functionalized, macroporous, organofunctional polysiloxane while Deloxan MP (2) is mercapto functionalized. 

Due to its high potency and selectivity imetit (24) proved to be a valuable tool in pharmacological trials related to H3 receptors, but in spite of that the potential toxicity of its isothiourea moiety emerges to impede further pharmacological development. A similar situation arose with the H3 antagonist thioperamide, the clinical development of which was ceased due to hepatotoxicity which is most probably related to its thiourea functionality. 

In Scheme 7 the protonation of TV-benzoylthiourea (I) is shown. Amide as well as thiourea functions may be expected to have reduced basicities. The interesting question is on which atom the protonation may take place on the oxygen or on the sulphur atom In fact, both the sulphur and the oxygen atom are protonated. The cause for this is the different acidity functions. 

Various heterocycle-fused thiadiazepines were synthesized by intramolecular cyclization of (o-aminoaryl)thio azaheterocycles. The un(substituted) benzimidazoles 109 (R2 = benzo) with thiourea-functionalized (Y = S ... 

Thiourea functions were used to attach chiral saccharide units to the molecule of calix[4]arene [72]. The complexation properties of these molecules toward chiral anions have not yet been examined. However, in the preliminary complexation studies (XH NMR titrations in DMSO-d6) the affinity toward acetate and AT-Ac-L-alaninate was observed. 

The ditopic receptors 66-68 containing crown ether and urea/thiourea functional groups have been synthesised. Compound 66 immobilised in the 1,3-al-... 

The Tang group combined the chiral pyrrolidine core with a thiourea function (Scheme 2.43) [29]. Optimal reaction conditions were obtained with 26 under solvent-free conditions and in the presence of n-butyric acid as additive (10 mol%) at 0 °C (Scheme 2.43). The high selectivity of the addition was attributed to the formation of a rigid three-dimensional H-bonded structure in the transition state, in which the enamine was positioned at the correct distance compared to the nitroolefin and allowed an addition from the Re-face of the enamine. 

Around the same time as this, Reinhoudt developed a calix[4]arene system with only two urea or thiourea functionalities attached on opposite faces 70-72 [167]. These less substituted systems display both inter- and intramolecular hydrogen bonding as a result of the calixarene adopting a pinched cone conformation (demonstrated by the use of NOESY NMR). In some spectra it is impossible for the connectivities to be made within a single molecule, so the only possibility left is that dimerisation occurs. As with the initial experiments of Rebek and Bohmer, the extent of hydrogen bonding was observed to be solvent dependent. Concentration dependant FTIR was also used, to observe the effects on the NH stretching vibrations, but no concentration dependence was observed. Of the three urea derivatives used, only 72 showed no evidence of dimerisation... 

A number patents and publications describe sedative or antidepressant properties for quinazolinethiones such as 3 related to the efavirenz lead Chemical instability of the lead structure 1, due to the masked ketone at the 4-position, was addressed by replacing the ethoxy group with a carbon linked substituent." A focus on replacing the thiourea functionality because of potential toxicity led to urea analogs, and subsequent efforts were directed toward solving the low metabolic stability of the /V-methyl group. This was attained by a switch to the benzoxazinone system... 

The thiourea functionality, inserted on the most frequently used chiral pyrrolidine scalTold, works excellently as reactivity and enantioselectivity control co-factor by chelating the nitro group of the acceptor. This solution, adopted in 25, provides a family of robust catalysts that afford high yields (up to 98%) and great stereoselectivities (up to 99 1 dr and 99% ee) in direct Michael additions of ketones to various nitroolefins in water. ... 

Polystyrene-divinylbenzene polymer matrices, with a thiourea functional group, show good selectivity towards iron and copper, and effectively bind and remove them, both in batch and column operations. The adsorption mechanism can be explained by the coordination between ligand and metal ions [12]. 

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