Thiourea, protonation

DCCI reacts with hydrazone derivatives or with the thiourea 83 to give nitrogen ylides such as 84 and hence by protonation 3-aminotriazolopyridines (88CC506, 93JCS(P1)705). A solution of iodine in pyridine reacts with propional... 

The calculated 13C NMR chemical shift of the carbonyl carbon of monoproton-ated benzaldehyde131,132 for the. E-form 102 (205.5 ppm) and that for the Z-form 103 (207.4ppm) agree well with the experimental shifts of 203.5 and 205.9 ppm, respectively. Protonation of a-substituted cinnamic acids such as 104 was studied by 13C NMR spectroscopy and IGLO-HF calculations.133 Protonated deltic acid (105) and related compounds,134,135 as well as protonated urea 106 (X = O)136 and thiourea 106 (X = S)137 have been investigated by 13C NMR spectroscopy and quantum chemical calculations.138... 

In a study of acid catalysed proton exchange in aqueous urea solutions, much faster rates have been found (A j = 9 x 10 M s ) (Void et al., 1970). This was ascribed to N-protonation. A higher rate is expected for a stronger base [pATg for urea is 0-8 or 1 6, according to Arnett (1963) and 0 18, according to Parry et al. (1969)]. The exchange of NH-protons of thiourea is acid-catalysed about 60 times as efficiently as that of N-methylacetamide (Void and Correa, 1970). 

The carbon in the isothiocyanate grouping is highly susceptible to nucleophilic attack by the peptide s free amino group. Overall addition to the C=N creates a thiourea derivative. Making the conditions strongly acidic then promotes nucleophilic attack by the sulfur of the thiourea on to the carbonyl of the first peptide bond, producing a five-membered thiazoline heterocycle. Proton loss occurs from the nitrogen, and this creates an intermediate that is equivalent to the addition product in simple acid-catalysed amide... 

From the first transition state (TSl, Fig. 1), the reaction path leads to the tetrahedral intermediate 1 (INTI). In the latter, the proton transfer from methanol to the tertiary amine function is completed (from 1.183 to 1.059 A), and the negative charge at the former carbonyl oxygen atom reaches its maximum. This charge is compensated by a further shortening of the bifurcated hydrogen bonds to 2.040 A (-0.103 A) and 1.765 A (-0.096 A) (Fig. 1). The thiourea moiety thus forms an oxyanion hole similar to the amide groups of the serine protease backbone [41]. 

The enolate anion in complex 3 is stabilized by three N-H O bonds that involve the protonated amine moiety (1.68 and 2.28 A) and one of the N-H groups (1.80 A) of the thiourea. In complex 3", the enolate is tilted from its original position to maximize the number of N-H O bonds. In this arrangement, all three N-H units are involved in the hydrogen bond network. 

Fig. 5 Optimized structures (B3LYP/6-31G(d)) of the stationary points located for the proton transfer between the thiourea derived catalyst and the enol form of acetylacetone. Bond distances characteristic for hydrogen bonds are given in Angstrom, bonds broken or formed are shown in red...

Two distinct reaction pathways can be envisioned for the C—C bond formation step of this catalytic process (see Scheme 3.7). According to the mechanism proposed by Takemoto et al. [30], the nitroolefin interacts with the thiourea moiety of complex 3 (Scheme 3.7, route A), forming a ternary complex, wherein both substrates are activated, and C—C bond formation can occur to produce the nitronate form of the adduct Alternatively, the facile interconversion between 3 and 3" may allow an interaction of the nitroolefin with the cationic ammonium group of the protonated catalyst (Scheme 3.7, route B). In both cases, ternary complexes result... 

These experimental results suggested a hydrogen-bonding mediated cooperative Bronsted acid catalysis mechanism (Scheme 6.28). Thiourea cocatalyst 9 is viewed to coordinate to mandelic acid 20 through double hydrogen-bonding, stabilizes the acid in the chelate-hke cis-hydroxy conformation, and acidifies the a-OH proton via an... 

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