Anilines side products from

As a side product in these reactions a novel bridged steroid alkaloid 230 is formed, presumable by an intermediate hydride shift in 227 from the benzylic position to the iminium ion to give a secondary amine, which then attacks the formed cationic benzylic position. This reaction becomes the main reaction with aniline, p-bromoaniline or nitroaniline in the presence of BF3 -OEt2 if a derivative of 224 is used containing a propyl instead of a propenyl side chain [61]. 

A series of pyrrolidines was conveniently prepared in a microwave-assisted double alkylation of aniline derivatives with alkyl dihalides in water in the presence of K2CO3 as a base (Scheme 1) [12,13]. Although the reaction mixture could be regarded as a multi-phase system, as neither reactant was soluble in the mildly basic aqueous medium, the microwave-assisted reaction proceeded readily without the use of phase-transfer reagents. The amount of side-reactions such as hydrolysis of bromides to alcohols in an alkaline reaction medium was substantially suppressed compared to the conventional thermal conditions. The reaction conditions were sufficiently mild to tolerate a variety of functional groups in anilines such as hydroxyls, ketones and esters. Alkyl bromides and tosylates were equally efficient as alkylating agents. Notably, isolation and purification comprised simply of phase separations (filtration or decantation) of the desired product from the aqueous media. 

The transition metal catalyzed synthesis of arylamines by the reaction of aryl halides or tri-flates with primary or secondary amines has become a valuable synthetic tool for many applications. This process forms monoalkyl or dialkyl anilines, mixed diarylamines or mixed triarylamines, as well as N-arylimines, carbamates, hydrazones, amides, and tosylamides. The mechanism of the process involves several new organometallic reactions. For example, the C-N bond is formed by reductive elimination of amine, and the metal amido complexes that undergo reductive elimination are formed in the catalytic cycle in some cases by N-H activation. Side products are formed by / -hydrogen elimination from amides, examples of which have recently been observed directly. An overview that covers the development of synthetic methods to form arylamines by this palladium-catalyzed chemistry is presented. In addition to the synthetic information, a description of the pertinent mechanistic data on the overall catalytic cycle, on each elementary reaction that comprises the catalytic cycle, and on competing side reactions is presented. The review covers manuscripts that appeared in press before June 1, 2001. This chapter is based on a review covering the literature up to September 1, 1999. However, roughly one-hundred papers on this topic have appeared since that time, requiring an updated review. 

Characterization of the products arising from regioisomeric dimethoxyani lines reveal unexpected byproducts such as 35 and 38. These byproducts presumably arise from competitive side-reactions of the electron-rich anilines and not from intermediates of the Martinet reaction. 

The potential of palladium-catalyzed aminochlorination reactions of alkenes dates back to their isolation as side products in aminocarbonylation reactions under copper(II)dichloride cocatalysis [47d]. These reactions were later developed further using copper(II) salts as co-oxidants or reoxidants, respectively, and concomitantly as halide sources. For example, Chemler showed that various aminohalogenation reactions proceed under palladium catalysis in the presence of potassium carbonate as base in moderate to excellent yields in the presence of an excess of the copper oxidant [80]. Both five- and six-membered rings 115 and 116 were formed under these conditions from allyl anilines 114 (Scheme 16.28). Among other examples... 

The conversion of furan acid 9 to the drug candidate 1 is straightforward (Scheme 7). The aniline side chain is installed via the mixed anhydride, and the activated fiiran is converted to the pyrrole by treatment with NH4OAC in hot N-methylpyrrolidinone (NMP). The latter reaction benefits from a particularly efficient work-up addition of water to the warm NMP solution induces crystallization of the product, which is filtered directly from the reaction mixture. HPLC purities of >98% are typical from this reaction, and the product can be recrystallized if further purification is needed. We struggled with one impurity, which was present at levels between 0.5-1.0% in the crude product recrystallization reduced the level to 0.3-0.5%. We initially did not Imow the identity of this impurity, other than by mass spectral analysis, which indicated a molecular ion of M+NH (1 has formula C17H17FN2O3, the impurity is... 

For many processes, how ever, it is necessary to employ a divided cell in which the anode and cathode compartments are separated by a barrier, allowing the diffusion of ions but hindering transfer of reactants and products between compartments. This prevents undesirable side reactions. Good examples of the need for a divided cell are seen in the reduction of nitjobenzenes to phenylhydroxylamines (p. 379) or to anilines (p. 376). In these ca.scs the reduction products are susceptible to oxidation and must be prevented from approaching the anode. The cell compartments can be divided with a porous separator constructed from sintered glass, porous porcelain or a sintered inert polymer such as polypropene or polytetra-... 

The synthesis of a triptan with a chiral side chain begins by reduction of the carboxylic acid in chiral 4-nitrophenylalanine (15-1). The two-step procedure involves conversion of the acid to its ester by the acid chloride by successive reaction with thionyl chloride and then methanol. Treatment of the ester with sodium borohy-dride then afford the alanilol (15-2). Reaction of this last intermediate with phosgene closes the ring to afford the oxazolidone (15-3) the nitro group is then reduced to the aniline (15-4). The newly obtained amine is then converted to the hydrazine (15-5). Reaction of this product with the acetal from 3-chloropropionaldehyde followed by treatment of the hydrazone with acid affords the indole (15-6). The terminal halogen on the side chain is then replaced by an amine by successive displacement by means of sodium azide followed by catalytic reduction of the azide. The newly formed amine is then methylated by reductive alkylation with formaldehyde in the presence of sodium cyanoborohydride to afford zolmitriptan (15-7) [15]. 

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