Thiourea primary amine-functionalize

The Tsogoeva group, in 2006, reported the introduction of newly designed bifunctional secondary amine-functionalized proline-based thioureas (95 and 96) and the primary amine-functionalized thioureas (97-99) for catalysis of the asymmetric addition of ketones to trans-P-nitrostyrenes (Figure 6.30) [260, 261]. Using... 

Figure 6.30 Secondary amine- and primary amine-functionalized biflinctional thiourea derivatives (15mol% loading) screened in the model Michael addition of acetone to tram-P-nitrostyrene in toluene at rt.

The Jacobsen group independently focussed on the development of primary amine-functionalized thiourea derivatives and published, in 2006, the thioureas 100-103 incorporating the established tert-leucine (amide) motif (Figure 6.14) and the diaminocyclohexane or diphenylethylenediamine chiral backbone, respectively (Figure 6.31) [262]. The catalyst screening was carried out in the asymmetric Michael addition [149-152] of 2-phenylpropionaldehyde, an a,a-disubstituted aldehyde, to 1-nitrohex-l-ene (at 20mol% loading, DCM, rt, variable equiv. of H2O)... 

Figure 6.31 Primary amine-functionalized thioureas screened in the asymmetric Michael addition of 2-phenylpropionaldehyde to 1-nitrohex-l-ene using DCM as the solvent.

The higher activity of primary amines in the reaction involving enones as Michael acceptors has also been extended to the use of different bifunctional catalysts (Scheme 3.19), which usually contain a primary amine functionality connected to a basic site by means of a chiral scaffold, as is the case in the use of 280 and 55. These diamine catalysts have been found to be excellent promoters of the Michael reaction of enones with cyclic 1,3-dicarbonyl compounds and malonates respectively, the tertiary amine basic site present at the catalyst structure being responsible for assisting in the deprotonation of the Michael donor in order to increase the concentration of the nucleophile species. In a different approach, bifunctional thiourea-primary amine catalyst 56a has also... 

Though dental afflictions constitute a very significant disease entity, these have received relatively little attention from medicinal chemists. (The fluoride toothpastes may form an important exception.) This therapeutic target Is, however, sufficiently Important to be the focus of at least some research. A highly functionalized piperazine derivative that has come out of such work shows prophylactic activity against dental caries. Condensation of the enol ether 1 of thiourea with ji-pentylisocyanate gives the addition product 1J. Reaction of this with diamine 78, derived from piperazine, leads to substitution of the methylthio moiety by the primary amine, in all likelihood by an addition-elimination sequence. There is thus obtained ipexidine (79). ... 

Aminodebromination of 4-bromo-l//-3-benzazepin-2-amine (25) with triethylamine occurs readily and results in formation of the quaternary salt 26 (see also Section 3.2.1.5.6.), whereas attempts to effect nucleophilic substitution of bromide with primary or secondary amines gives only tarry mixtures.41 The bromo group is also resistant to displacement by azide and benz-cncthiolate but undergoes substitution with thiocyanate ion in hot dimethylformamide to give the 4-thiocyanato derivative 27 rather than the thiourea by addition at the amine function. 

Primary amines can be derivatized on the free N-H functionality and therefore can be modified to an array of products. Thus, ureas 75,54 thioureas 74,58 guanidines 62,58 and carboxamides 7654 were prepared in excellent yields (see Scheme 14). 

The utility of urca.s and thioureas as substrates for making imidazoles is limited by the fact that the imidazole 2-substituent can only be an oxygen or sulfur function. Synthetic methods involving ureas and thioureas will also be discussed in Section 4.1, but some cyclizations of suitably functionalized species fall under the present heading. Appropriately substituted ureas and thioureas can be made from isocyanates and primary amines [36-38], from isocyanates and hydrazines [39] or thiocyanates and hydrazines [40], from or-aminonitrilcs and carbon dioxide [41] and by heating l,3,4-oxadiazol-2-oncs with amino acids [42]. Some of the substrates prepared in these ways, though, lead ultimately to reduced imidazoles such as hydantoins. Cyclizations arc usually acid catalysed, but they can also be thermal [43]. 

A bifunctional ligand was attached to different generation of ethylenediamine cored polyamidoamine dendrimer (PAMAM). Then Gl, G2 or G4 PAMAM dendrimer (8, 16 or 64 terminal primary amines) were mixed in water with an equimolecular amount of DOaAP 295c per number of primary amine (Scheme 62). Gd(III) and Gd(III)/Y(lll) complexes were prepared by mixing 2 equiv. of metal cation per thiourea function and removing the excess by washing with disodium EDTA [226, 227]. The reaction was extended to the fourth... 

Isocyanates and isothiocyanates react with primary amines to give urea and thiourea derivatives respectively. However, isocyanates react quite readily with water and alcohols to give urethanes. For this reason they are generally replaced by the less reactive isothiocyanates. However, a-naphthylisocyanate was recommended for the determination of lipids with a hydroxyl function [214] and may also find application in amino acid analysis. 

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