Amines, acetylation arylation

The thermolysis of aryl azides in alcoholic solution has been used to prepare 2-alkoxy-37f-azepines. Thermolysis of 3-azidophenyl methyl ketone in methanol in a sealed ampule furnishes a mixture of the 6-acetyl- (36a) and 4-acetyl-2-methoxy-3//-azepine (37a) in superior yields to those obtained in the corresponding photolytic reaction.78 Other 3-substituted azides behave similarly, with a preference for the 6-substituted isomers 36, as is observed for azide photolyses in amine solutions. 

BINOL phosphate (5)-3o (10 mol%, R = 2,4,6- PTj-C Hj) turned out to be the catalyst of choice and gave iV-acetylated 3-indolyl amines 128 bearing a qnatemary stere-ogenic center in excellent yields (94-99%) with high enantioselectivities (73-97% ee). Enamides derived from aryl-methyl ketones as well as indoles with varions substitnents conld be employed. 

The effect of temperature on the reduction of nitro-alkanes has been extensively exploited in the synthesis of cp-ephedrine analogues [i5,21,22] starting from 1-aryl-2-nitropropenes which are easily converted to the substrates 2. Reduction of these nitrocompounds below 20° C affords the hydroxylamine. The amine is formed above 55° C. Neutralisation of either reaction mixture causes rapid intramolecular migration of the acetyl group from oxygen to nitrogen, a reaction which implies a... 

For the isomerization, strongly basic amines are required as substrates. Allyl-amines bearing N-aryl groups retard the reaction. Allylamides are slow-reacting substrates and require a higher reaction temperature. Thus, N-acetyl-4-methyl-tet-rahydropyridine (16) can only be subjected to isomerization at 150 °C. After a reaction time of 15 h the optically active enamide was obtained in 98 % ee. 

Finally, ortho- 2,2-dibromovinyl)-aniline or -acetanilide can successfully be applied in a sequential cyclizing amination-cross coupling reaction with diethyl phosphonate to furnish the indolyl phosphonic ester 136 or the N-acetyl 2-aryl indole 137 as recently shown by Bisseret and coworkers [ 105] (Scheme 50). This sequence can be also performed with corresponding phenol derivatives furnishing benzofurans. For the N-acetyl 2-aryl indole 137 it can be shown that the Suzuki coupling occurs prior to the intramolecular animation as a consequence of the gradual difference in reactivity between trans-and czs-carbon-bromine bonds. 

Acetyl-1 -alkyl-3,3-dimethyl- E16c, 442 (Br-C-C-Br +Amin) lrans- -Anilinocarbonyl-2-aroyl-3-aryl- E16c, 577 (N-Acylio.)... 

Indol 1-Acetyl-4,6-dibrom- E6b/1, 706 [N-Acyl-N-aryl-hydroxyl-amin -I- H2C = CH —O —Ac/ Pd(II)]... 

The N-alkylation of amides followed by hydrolysis furnishes a good route for making secondary amines. The formyl, acetyl, and aryl-sulfonyl " derivatives of amines are best suited for alkylation (method 358). Hydrolysis is accomplished by refluxing concentrated hydrochloric acid alone or in acetic acid. N-Alkyl-formamides prepared by the addition of olefins to nitriles (method 355) are hydrolyzed with aqueous alkali. Similar hydrolytic procedures... 

Microwave irradiation of a mixture of an acid anhydride, an amine adsorbed on silica gel, and TaCl5/Si02 is a solvent-free method for the synthesis of A-alkyl and A-aryl-imides [47]. Ni(II) promotes the conversion of an acrylamide to ethyl acrylate via a Diels-Alder adduct with (2-pyridyl)anthracene [48], Aromatic carboxylic acids [49] and mandelic acid [50] are efficiently esterified with Fc2(S04)3 XH2O as catalyst. Co(II) perchlorate in MeOH catalyzes the methanolysis of acetyl imidazole and acetyl pyrazole [51]. Hiyama et al. used FeCb as a catalyst for the acylation of a silylated cyanohydrin. The resulting ester was then cyclized to 4-amino-2(5H)-furanones (Sch. 5) [52]. 

Polycyclic aromatic amines are readily absorbed into the body via the gastrointestinal tract, where metabolic activation takes place. Aryl amines are N-hydroxylated and subsequently glucuronidated via uridine diphosphate (UDP)-glucuronosyl transferase or sulfated by sulfotransferases, N-acetylation of the amine, and 0-acetylation of the N-hydroxy amine can occur. 

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