High-Yield Syntheses of N-Mono- And N,n-Di-Substituted Ureas and Thioureas From Silicon Pseudohalides

Abstract

This study demonstrates that N-mono-and N,W-di-substituted ureas and thioureas tnay expediently be synthesized, in essentially theoretical yield, by reacting primary or secondary aliphatic, alicyclic, aralkyl, aromatic, and heterocyclic amines with silicon tetraisocyanate or tetraisothiocyanate, or the corresponding methyl-substituted analogues. The method fails with aromatic amines possessing bulky (e.g. phenyl, bromo), or strongly electronegative (e.g. trifluoroinethyl), substituents in the 2-, or 2,6-positions of the aromatic nucleus. Data on several new substituted ureas and thioureas are reported, and improved preparative procedures for the silicon pseudohalides are described. I t has long been known that organic isocyanates and isothiocyanates react readily with primary and secondary aliphatic and aromatic anlines to produce substituted ureas and thioureas. Indeed, these reactions are conlmonly employed to characterize amines and to prepare urea derivatives (1, 2). Despite the large amount of literature available on con~pounds containing the carbon-isocqanate and carbon-isothiocyanate groups, very few studies have been published on the reactions of amines with compounds containing the silicon-isocyanate (Si-NCO) and silicon-isothiocyanate (Si-NCS) groups.In 1951, Anderson (3) reported that silicon tetraisocyanate and several alkyl-and arylsilicon mono-, di-, and tri-isocyanates and isothiocyanates react readily with aniline, but the products resulting from these reactions were not characterized. Later, O'Brien (4) showed that trimethylsilicon isocl-anate in benzene solution reacts with n-, i-, s-, and t-butylamines t o produce butylureas. In 1958, Neville (5) demonstrated that silicon tetraisocyanate and isocyanates of empirical formula R,Si(NCO),-, (R = Ale, Ph; x = 0, 1, 2, 3) reacted alone or in benzene solutioil with ally-lainine, diallylamine, aniline, benzylamine, and o-and 9-toluidines to produce essentially theoretical yields of the corresponding N-mono-or K,N-di-substituted ureas. In every case the isocyanates and amines reacted in stoichiometric proportions and intermediate silylureas were not isolated. T h a t these reactions do, in fact, i~lvolve silylurea intermediates was shown by Goubeau and Heubach (6), who reacted aniline and several secondary aliphatic amines with methylsilicon isocyanate~, ;\lezSi(NCO)4-z (x = 0, 1, 2, 3), in petroleum ether." The silylureas isolated

Iodocyclisation of N-allyl ureas; a route to imidazolin-2-ones

“…9 Reaction of the allylamines 2-5 with trimethylsilyl isocyanate gave the required ureas 6-9 in good yield (Scheme 3). 10 In order to ensure that the iodocyclisation of the N-allyl ureas proceeded via nitrogen, rather than oxygen, we followed the procedure developed by Knapp for cyclisation of related unsaturated amides.…”

“…The solution was heated under reflux for 1 h and after cooling, the product partially precipitated from the solution as a colourless solid and was filtered off. The remaining product was obtained after the solvent was evaporated to give the title compound (0.85g, 85%) as platelets, mp 85-87 °C, (lit., 10 N,N-Methylallylurea 7. N-Methylallylamine 3 (0.5 ml, 5.5 mmol) was added via a syringe to dry benzene (10 ml) under nitrogen and TMSNCO (0.8 ml, 6 mmol) was added to the stirred solution.…”

Saxitoxin

“…Die anschließende Umsetzung dieser Verbindung zu dem Thioharnstoff 6 ist besonders bemerkenswert, weil hierfür das Reagens Si(NCS) 4 eingesetzt wurde, das seit seiner Einfüh-rung durch Neville 1963 in der organischen Synthese nur selten Anwendung gefunden hat. [70] Der Ringschluss erfolgt vermutlich durch eine 6p-Elektrocyclisierung der Zwischenstufe 2 und führt zum ersten von drei bençtigten Chiralitäts-zentren. Nach Beendigung der Synthese von racemischem STX lieferte eine modifizierte Sequenz mit (R)-Glyceraldehydacetonid anstelle von Benzyloxyacetaldehyd das Thioharnstoffprodukt 10 als 9:1-Diastereomerengemisch (Abbildung 9).…”

“…[65] 3. De-novo-Synthese von Saxitoxin [70] Der Ringschluss erfolgt vermutlich durch eine 6p-Elektrocyclisierung der Zwischenstufe 2 und führt zum ersten von drei bençtigten Chiralitätszentren. Nach Beendigung der Synthese von racemischem STX lieferte eine modifizierte Sequenz mit (R)-Glyceraldehydacetonid anstelle von Benzyloxyacetaldehyd das Thioharnstoffprodukt 10 als 9:1-Diastereomerengemisch (Abbildung 9).…”

A Convenient Method for the Preparation of N,n′-Disubstituted Thioureas Using 2-Chloropyridinium Salt, Sodium Trithiocarbonate and Amines

“…A possible mechanism is shown in path A of the scheme. First, [1] reacts with [2] to afford a reactive intermediate [3]6) easily, and then an amine attacks a carbon atom on thiocarbonyl group of [3] giving N,N'-disubstituted thiourea and [4]. Existence of the other path was also suggested because the reaction of [1] with [2] in CH2C12 at reflux for 1 hr gived [4] in 28 % yields besides the quantitative formation of NaCl.…”