Propargylamine derivatives

A unique method to generate the pyridine ring employed a transition metal-mediated 6-endo-dig cyclization of A-propargylamine derivative 120. The reaction proceeds in 5-12 h with yields of 22-74%. Gold (HI) salts are required to catalyze the reaction, but copper salts are sufficient with reactive ketones. A proposed reaction mechanism involves activation of the alkyne by transition metal complexation. This lowers the activation energy for the enamine addition to the alkyne that generates 121. The transition metal also behaves as a Lewis acid and facilitates formation of 120 from 118 and 119. Subsequent aromatization of 121 affords pyridine 122. 

Using propargyl alcohols and propargylamine derivatives as acetylenic compounds, the silylformylation reaction affords, in the presence of a base, a-silylmethylene-P-lactones, I, and P-lactams, II, respectively (Scheme 3) [13]. 

Reaction with Propargyl Halides. The indium-mediated coupling of propargyl bromide with a variety of imines and imine oxides afforded homo-propargylamine derivatives in aqueous media under mild conditions.78 Propargylation of glyoxylic oxime ether in the presence of a catalytic amount of palladium(O) complex and indium(I) iodide in aqueous media was also studied (Eq.11.47).79... 

Pyrroles and fiirans were prepared by the intramolecular carbon-carbon bond formation between pendant acetylene and nitrile or carbonyl functions. The process, running in acetic acid, starts by the fraw-acetoxypalladation of the acetylene moiety, which initiates a series of further transformations. The nature of the ring formed is determined by heteroatom bridging the two reactive units. The propargylamine derivative in 3.88., for example gave a pyrrole ring.112... 

Cserhati, T. Forgacs, E. Influence of the physicochemical parameters of propargylamine derivatives on their retention on a-cyclodextrin polymer-coated support. J. Liq. Chromatogr. Relat Technol 1995,18 (14), 2783. 

Konno T, Moriyasu K, Ishihara T. A remarkable access to y-fluoroalkylated propargylamine derivatives or fluoroalky-lated dihydroisoxazoles via the reaction of fluoroalkylated acetylides with various nitrones. Synthesis 2009 1087 1094. 

Etintidine (84), an imidazole-containing histamine H-2 receptor antagonist, is an antiiilcer agent conceptually related to cimetidine and ranitidine. It can be synthesized by various routes one of which terminates by an addition-elimination reaction of propargylamine with substituted N-cyano-S-methylisothiourea derivative 83 to give etintidine (84) [28]. 

A versatile synthesis of triazolopyrazines has been elaborated by Akritopoulou-Zanze et al. <2004TL8439>. The method involves two steps a multicomponent Ugi reaction and a subsequent ring closure. Thus, arylaldehydes, propargylamine, cyclohexylisocyanide, and azidoacetic acid yielded the intermediate 406 which easily underwent cyclization to give the partially saturated derivative 407 in excellent yields. 

As far as propargyl thioethers are concerned, the substrates in this section follow all the principles discussed for propargyl ethers and propargylamines in the two preceding sections. For alkyl propargyl thioethers typical bases used are sodium amide in liquid ammonia, alcoholate or alkali metal hydroxide [178, 186-189, 191, 287-291], and again some derivatives of carbohydrates have been used successfully [292, 293], If an ester group is also present in the molecule, the reaction can be accompanied by a hydrolysis to the carboxylate [294]. 

The protected propargylamines 224 (R = H, CH2C02Me or CH2CH2C02Me) react with aqueous formaldehyde under copper bromide catalysis to yield the allene derivatives 225. Deprotection with ethereal hydrogen chloride affords the free amines218. 

Additionally, dimedone derivative 241 and propargylamine 234 could be combined to give the alkynyl vinyl amine 242. The rearrangement/cyclization cascade could be induced upon heating until reflux in chlorobenzene. The an-... 

In the absence of basic catalysts, propargylamines react with isocyanates to give ureas. However, in the presence of basic catalysts, 4-methylene-2-oxazoli-dinones and 4-methylene-2-imidazolidinones are obtained directly or through the urea derivative [27] (Eq. 18). 

The benzothiazepine ring 41 could be substituted at C-2 with propargylamine nucleophile, apparently without desulfurization, leading to an imidazole derivative 42 fused with a benzothiazepine (Equation 2) <1995EJM429, 1993FA665>. 

The most commonly used MAO inhibitors include hydrazines, such as iproniazid, Marsilid, Marplan, Niamid, Nardil, Catron also nonhydrazines such as propargylamines, cyclopropylamines, aminopyrazine derivatives, indolealkylamines, and carbolines. MAO-inhibiting materials discussed in this book include yohimbine various tryptamines, especially 5-MeO-DMT and the alpha-methyltryptamines and the various harmala alkaloids. The latter are especially potent inhibitors, but, like yohimibine and the tryptamines, are short-lasting in action (30 minutes to several hours). Some of the commercial MAO inhibitors listed above are effective for several days to several weeks. 

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