Isocyanates, amino functionalization

It is well established that primary amino-functional groups, particularly aliphatic ones, react instantaneously with isocyanates to form ureas at ambient temperature. Indeed this was observed when 6-aminoethylferrocene (3) and freshly distilled phenylisocyanate were shaken vigorously. A yellow precipitate separated out immediately. Elemental analysis and an IR spectrum of the product indicate this compound to have the structure 6. ... 

This reaction takes place because diimides, —N=C=N—, have reactive cumulated double-bond systems like those of ketenes, C=C=0 isocyanates, —N=C=0 and isothiocyanates, —N=C=S and are susceptible to nucleophilic attack at the central carbon. In the first step of the diimide-coupling reaction, the carboxyl function adds to the imide to give an acyl intermediate, 9. This intermediate is an activated carboxyl derivative RCO—X and is much more reactive toward an amino function than is the parent acid. The second step therefore is the aminolysis of 9 to give the coupled product and yV,N -dicyclohexylurea ... 

Related methods may be used to introduce amino functions. For example, thiocyanate 237, made from the 4,6-dimesylate, rearranges to the isothiocyanate 238,225 and 3,4-unsaturated 2-cyanates, easily made in situ from the corresponding carbamates, afford the A-bonded 4-isocyanates of the 2-enes.229 From both types of rearranged products aminodeoxy sugars may be accessed, and in this way perosamine peracetate (239) can be synthesized from the cyanate of a 3,4-unsaturated 2-ol, which is thermally rearranged prior to dihydroxylation and acetylation.229... 

The isocyanate can be replaced by the corresponding activated urethane (as a milder reagent), and this activation can also involve the p-amino functions of the calix[4]arene (step e) and their subsequent reaction with a suitable amine (step f). Multigram quantities of simple tetra-urea calix[4]arenes are easily available in this way. 

Forosamine is an amino sugar component of the antibiotic Lepicidin. Since Le-picidin is sensitive to acid and catalytic hydrogenation, an Fmoc group was selected to protect the amino function. A rather unconventional method was used to introduce it [Scheme 8.94].230 A Curtius rearrangement on the acyl azide derived from carboxylic acid 94.1 proceeded with retention of configuration to give the isocyanate intermediate 94.2 that was trapped with 9-fluorenylmethanol to afford the N-Fmoc derivative 94J in 72% yield. 

Semiaminal (567) reacted with nucleophiles generally by a replacement of the hydroxy group Only few exceptions were known. For example, reaction of 567 with ketene or isocyanates caused acylation and displacement of the secondary amino moiety (equation 147) cyclopropanone (84) could be detected spectroscopically in one case. A similar removal of the amino function by tosyl isocyanate (571) was observed with 570, but here compound 574 was isolated in 47% yield (equation 148). 574 resulted from a subsequent addition of the initially formed products 572 and 573 . Steric reasons led to the sequence 570 - 574 the diastereomeric endo-morpholino semiaminal reacted with 571 by displacement of the exo-hydroxy group. 

Despite the transformation of a certain number of amino groups into urea groups, the qualitative shape of the zeta-potential plots as a function of pH is not changed significantly. That indicates that PVFA-co-PVAm can be used as a precursor polymer for the gradual functionalization of silica particles and other Bronsted-acidic surfaces with amino functionality. Chemical reactions of PVFA-co-PVAm/silica particles with isocyanates or other electrophilic reagents offer a wide field of applications, because of the simple experimental procedure this material combination seems promising for the construction of tailor-made polyelectrolyte networks on Bronsted-acidic surfaces or for other multicomponent systems. 

Primary phosphorothiosulphenamides may be acylated, and with sodium ethoxide they are converted into trialkyl phosphorothionates. Other reactions of phosphorothiosulphenamides include the loss of sulphur upon treatment with sodium, and translocation of the amino-function when treated with thiophosphoryl halides. Treatment of the acyl chloride (71) with ethyleneimine gives an amide which undergoes ready conversion into the isocyanate (72). ... 

One of the most versatile transformations with subsequent hetero-cyclization is the smooth and mostly exothermic addition of electron-poor isocyanates to the 2-amino function of almost all types of heterocyclic enamino esters (cf. 87). A mixed urea (88) is first formed it can be easily isolated but in most cases is cyclized in situ with aqueous base to afford heterocondensed uracils (89) in high yields71 (Scheme 23). This reaction... 

The alternative [2 + 2] cycloaddition route to azetidinones, using chloro-sulphonyl isocyanate and functionalized alkenes, has been further used in syntheses of /8-lactam antibiotics. Asymmetric induction in the formation of /3-amino-aa-dimethyl-/8-phenylpropionic acid has been achieved, using a Reformatsky reagent and a chiral Schifif base, the reaction proceeding through a /3-lactam intermediate. ... 

Related reactions of thiolate anions with ort/zo-chloromethyl-phenyl(diphenyl)phosphine have provided a range of ort/ o-alkyl and aryl-thiomethylphenyl(diphenyl)phosphines. " The reactions of 2-amino-alkylphosphines with isocyanates and isothiocyanates have provided routes to new chiral phosphinoalkyl-urea and -thiourea ligands. Similarly, treatment of hydroxy- or amino-functional arylphosphines with isocyanides in the presence of a cyclooctadienepalladium(II) complex results in the formation of bidentate arylphosphino-carbene palladium complexes. New chiral phosphinoarylphosphoramidite ligands, e.g.,... 

Nitrocellulose based lacquers often contain short or medium oil alkyds to improve flexibiUty and adhesion. The most commonly used are short oil non drying alkyds. Amino resins or urethane resins with residual isocyanate functional groups may be added to cross-link the coating film for improved solvent and chemical resistance. The principal appHcations are furniture coatings, top lacquer for printed paper, and automotive refinishing primers. 

Reaction with Phosgene. This reaction of amino acid esters is used for preparing the corresponding isocyanates, especially lysine diisocyanate [4460-02-0] (LDI). LDI is a valuable nonyellowing isocyanate with a functional side group for incorporation in polyurethanes. 

Urethane sealants have good inherent adhesion to most substrates, but silane adhesion promoters are often used to improve this adhesion. Epoxy-, amino-, and mercapto-functional silanes are the most common because of their dual reactive nature. The silane end can react with surface hydroxyls the epoxy, amino, or mercapto end can react with the isocyanate. 

Urethane hydrolyzes into an amine, an alcohol, and carbon dioxide. So the possible degradation products of a poly(phosphoester-urethane) are diamines, diols, phosphates, carbon dioxide, and even ureas. Urea is possible because the isocyanate is extremely sensitive to moisture, which would convert the isocyanate to an amino group. One is therefore bound to have traces of diamine in the polymerization that leads to a urea bond in the backbone. We think the cytotoxicity seen in the macrophage functional assay comes from the TDI structure. 

Finally, the Lessen rearrangement provides a practical procedure for replacing the hydroxamic group of a hydroxamic acid (12) by an amino group (14) (equation 2). The initial rearrangement product is an isocyanate (13) which readily reacts with nucleophiles, for example with OH and NH functionalities to give amines (14) and ureas (15). 

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