Thiourea addition with

Other types of conjugate additions with chiral thioureas were also explored by Connon. P-Substituted nitro-olefms were used in the conjugate addition reaction with dimethyl chloromalonate 115 to generate chiral, functionalized nitrocyclopro-panes [73]. Utility of the nitrocyclopropanes was demonstrated in the one-step modification towards other functionalized chiral building blocks (Scheme 24). 

The scope of Michael additions with catalysts containing cyclohexane-diamine scaffolds was broadened by Li and co-workers [95]. When screening for a catalyst for the addition of phenylthiol to a,p-nnsatnrated imides, the anthors fonnd that thiourea catalyst 170 provided optimal enantioselectivities when compared to Cinchon alkaloids derivatives (Scheme 41). Electrophile scope inclnded both cyclic and acyclic substrates. Li attributed the enantioselectivity to activation of the diketone electrophiles via hydrogen-bonding to the thiourea, with simultaneous deprotonation of the thiol by the tertiary amine moiety of the diamine (170a and 170b). Based on the observed selectivity, the anthors hypothesized that the snbstrate-catalyst... 

B. A 25.00-mL sample containing Fe3+ and Cu2+ required 16.06 mL of 0.050 83 M EDTA for complete titration. A 50.00-mL sample of the unknown was treated with NH4F to protect the Fe3+. Then Cu2+ was reduced and masked by thiourea. Addition of 25.00 mL of 0.050 83 M EDTA liberated Fe3+ from its fluoride complex to form an EDTA complex. The excess EDTA required 19.77 mL of 0.018 83 M Pb2+ to reach a xylenol orange end point. Find [Cu2+] in the unknown. 

The reaction of N,N -disubstituted thioureas 15 with phosgene (carbonyl chloride) affords aliphatic and aromatic carbodiimides 16 in good yields. For example, addition of phosgene... 

Acrylates can also be used in Michael addition with primary amine and, after further reaction with isothiocyanate, supported thioureas are isolated. These can then undergo a cleavage under basic conditions leading to cyclisation and formation of tetrahydrothioxopyrimidinones [129], Onium salts supported isothiocyanates can also be used with this methodology and lead to the formation of various guanidines [130] (Fig. 41). 

A more simple thiourea catalyst with amino functionality catalyses the asymmetric Michael addition of 1,3-dicarbonyl compound to nitroolefin [29,30]. In the reaction of malonate to nitrostyrene (Table 9.11) the adduct is satisfactorily obtained when A-[3,5-bis(trifluor-omethyl)phenyl]-A -(2-dimethylaminocyclohexyl)thiourea is used as a catalyst (ran 1), whereas the reaction proceeds slowly when the 2-amino group is lacking (ran2). In addition, chiral amine without a thiourea moiety gives a poor yield and enantioselectivity of the product (run 3). These facts clearly show that both thiourea and amino functionalities are necessary for rate acceleration and asymmetric induction, suggesting that the catalyst simultaneously activates substrate and nucleophile as a bifunctional catalyst. 

Yoon et al. [33] found that thiourea catalyst with an amine function promotes the stereoselective addition of a range of nitroalkanes to aromatic A-butoxycarbonyl (A-Boc) imines. In the Mannich reaction of nitroethane (Table 9.12) high enantioselectivity, but low yield, is observed when urea is used (run 1), whereas thiourea affords the adduct in >95% yield with 92% ee (run 2). It should be noted that addition of powdered molecular sieves is necessary for reproducible results. 

Thiourea catalyst with a modified cinchona alkaloid unit is applied to intramolecular Michael addition of phenol chiral chromanone is produced in high yield with good... 

Thiourea catalyst with additional thoiurea functionality can act as possible bifunctional thiourea catalyst due to the hydrogen bonding ability of the thiourea function. C2-symmetric bisthiourea has been applied to the Baylis-Hillman reaction of cyclohexenone [42] (Table 9.14). Adduct is obtained in moderate to good yields (runs 1-6), but asymmetric induction is dependent upon the aldehyde electrophile (90% ee in run 6). The use of monothiourea as a catalyst results in low conversion (20%). Thus, it could be reasonably deduced that each thiourea function of bisthiourea independently and effectively interact with cyclohexenone and aldehyde in the transition state (Figure 9.10). 

The addition of nitroalkanes to chalcones is more attractive since the Michael adducts are useful intermediates for a variety of further elaborated stmctures such as chiral aminocarbonyls, pyrrolidines, y-lactams, and y-amino acids. Thus, many elegant organocatalysts such as cinchona alkaloid-derived chiral tertiary amine thiourea 69 [67] or suqaramide 70 [68] and bisquaternary ammonium salts [69] 71a or 71b have been developed for such a reaction in recent years (Scheme 5.33). In addition, a,(3-unsaturated A -acylpyrroles [70] and 4-oxo-enoates [71] were also applicable in the highly enantioselective conjugated addition with nitroalkanes (Scheme 5.34). 

Aminothiourea-prolinal dithioacetal (234), in the presence of PhC02H, can catalyse Michael addition of ketones R CH2COR and aldehydes to nitroalkenes at 3 mol% loading to afford the 3yn-configured products with <99 1 dr and <99% ee under solvent-free conditions at room temperature. The related carbohydrate-derived thiourea is believed to activate both 8-diketones and nitroalkenes via coordination (235) the Michael adducts were obtained in <89% ee " Another variant of the thiourea motif with a cinchona alkaloid scaffold exhibited higher stereocontrol in the same reaction (<98% ee), carried out in MeCN at —40°C ... 

In addition to these standard methods, a number of specialized reactions of limited scope have been used to prepare some biologically important S-labelled thiols. For instance, 2-thiouracil- S has been prepared by the condensation of thiourea- S with Na0CH=CHC02Et . a-Amino- -mercaptobutyric acid- S was prepared by the acid hydrolysis of 4-carboxy-5-methyl-2-phenylthiazoline- S 2,3-Dimercaptosuccinic acid- S2 was obtained by the hydrolysis of 2,3-bis(acetylthio)succinic acid- S. D,L-Cysteine- S was obtained by the acid hydrolysis of PhCOS-CH2CH(HNCOC0H5)CO2Me... 

In some cases hexamethoxymethylmelamine was substituted for a portion of the formaldehyde used to prepare the resins. For example, resins have been reported to be prepared by reaction of resorcinol with hexamethoxymethylmelamine and thiourea along with additional formaldehyde at pH 7.3 (adjusted with KOH) [76]. 

Reacting substances sulfides, thiophenols, thioesters, sulfilimines, thioanilides, thioureas, isothiocyanates, and xanthogenates. If the test for the sulfidic sulfur is negative, the main filtrate is mixed with three drops of 30% hydrogen peroxide, boiled, acidified with dilute hydrochloric acid (1 1), and additioned with three drops of a 10% barium chloride solution. 

Alkyl halide (10 — 25 mg) is mixed with 0.5 ml of a 2% acetonic thiourea solution and heated in a sealed glass ampoule in a water bath for various time intervals iodides, 1 hr bromides, 2 hr chlorides (if the mixture was additioned with 10 mg of sodium iodide as catalyst) 3 hr. After cooling, the ampoule is opened and the contents transferred into a small test tube, and the solvent is evaporated on a water bath. The residue is dissolved in two drops of water and mixed by dropwise addition and shaking with 1 ml 2% aqueous sodium 3,5-dinitrobenzoate solution. The separatedamo rphous product is dissolved by immersing the test tube into a hot water bath, and is then allowed to crystallize by slow cooling. The product is recrystallized from 0.5 — 1 ml of hot water. 

The asymmetric conjugate addition with thiol nucleophiles was demonstrated using 2-mercaptobenzaldehydes. The utiUty of the same chiral cyclohexane-diamine catalysts 35 mediated the domino Michael-aldolof 2-sulfanylbenzaldehydes with maleimides (Scheme 13.10) [28]. The products of the reaction consist of fused heterocycles in high yield and high enantiomeric ratios. The stereochemical outcome sheds insight into the proposed mechanism whereby the catalyst simultaneously activates the thiol group via the cyclohexyl tertiary amine while the maleimide is stabilized by the thiourea component... 

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