Benzylamine, basicity nucleophilicity

A kinetic smdy has been reported of substituent effects on the reactions of 2-phenoxy- and 2-(4-nitrophenoxy)-3-nitro-5-X-thiophenes with benzylamine and with A-methylbenzylamine in benzene as solvent. The intramolecularly hydrogen-bonded intermediate (14) is postulated. Reactions of the 5-unsubstimted thiophenes (X = H) are not base-catalysed, indicating that nucleophilic attack is rate limiting, and the more basic secondary amine shows higher reactivity than the primary... 

Whereas ammonia is an unsuitable nucleophile towards 7r-allylpalladium complexes, primary amines often participate well. Benzylamine and 4,4 -dimethoxybenzhydrylamine are especially useful, since subsequent removal of the benzylic substituents permits their use as ammonia equivalents. Such a deblocking procedure was used in a short synthesis of the enzyme inhibitor gabaculine from amino ester 1118. An allyl carbonate can be successfully employed as a substrate for palladium(0)-catalyzed animation to give 1219,20, but experimental difficulties have been experienced with a structurally similar carbonate9. As shown by the formation of 1016 and by the partial production of 13 prior to basic hydrolysis16, additional attack on an ester function may occur. Amino alcohols 13, formed with complete regioselectivity due to steric reasons, have been efficiently converted into isoquinuclidines16. 

Several reports of the reactions of /Fsultams with amines have been recorded. The sultams 122 and 123 are converted by the action of benzylamine to the corresponding sulphonamides (equation 215)242,269-27. Functionalized /Fsultams often undergo C—N bond fission under nucleophilic/basic conditions as shown in equation 216258. Whilst both 1,8-naphthosultam and its N-methyl derivative are essentially stable towards... 

When dibromide (23) was reacted with nucleophiles, the formation of (24) was problematic, particularly with strongly basic reagents. However, sodium sulfide and primary amines were found to give satisfactory yields of heterocycles (25) and (26a-c), respectively [7,33]. The benzylamine 26c was subsequently converted into various other derivatives (Scheme 6.8). 

Jones et al. (67) also prepared a wide range of water soluble ammonium dithiocarbamate salts, [NH4][S2CNR2] (Fig. 5). They result from the iifitial reaction of the amine with concentrated aqueous ammonia in ethanol, followed by later addition of carbon disulfide at low temperatures. For example, diethanolamine, HN(CH2CH20H)2, forms a yellow precipitate in 65% yield. Castro et al. (68) studied the kinetics and mechanism of the reactions of piperidine, pyrrolidine, morpholine, and benzylamine (69) with carbon disulfide in ethanol (Fig. 6). They proceed via a dithiocarbamic acid intermediate (4), which in turn yields the dithiocarbamate anion (5) upon proton loss to the amine. While for pyrrolidine, formation of the dithiocarbamic acid is rate determining and proceeds to the dithiocarbamate irreversibly, for both morpholine and benzylamine, the transformation is reversible. Further, in these cases the ethoxide anion is found to catalyze the transformations. They have also determined that pyrrolidine is 200 times more nucleophilic toward carbon disulfide than piperidine, despite the later being only slightly more basic, a feature that may relate to the irreversible nature of the formation of pyrrolidine dithiocarbamate. 

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