N-Amination of Pyrrole and Indole Heterocycles with Monochloramine (NH₂Cl)

Abstract

A survey of several electrophilic ammonia reagents for the N-amination of indole- and pyrrole-containing heterocycles revealed that monochloramine (NH(2)Cl) is an excellent reagent for this transformation. Pyrroles and indoles containing a variety of substitution were aminated on nitrogen with isolated yields ranging from 45% to 97%.

Cycloadditions of 1,2,3-Triazines Bearing C5-Electron Donating Substituents: Robust Pyrimidine Synthesis

“…15 Subsequent N -amination of 11 with monochloramine 16 provided a mixture of N -amino pyrazole 14 and starting 11 (74%, 98% brsm, ~3.4:1) that was inseparable by chromatography. Nevertheless, when the mixture of N -amino pyrazole 14 and pyrazole 11 was treated with NaIO 4 under biphasic oxidative ring expansion conditions 17 , 5-(methylthio)-1,2,3-triazine ( 17 ) (56–74%) was obtained in good yield and was readily separable from products derived from pyrazole 11 .…”

Five‐Membered Heterocycles: Pyrrole and Related Systems

“…A series of 1-aminopyrroles, including 406, has been prepared by Namination of the corresponding NH-pyrroles with anhydrous ethereal NH 2 Cl in the presence of NaH [638]. Recently, a more convenient N-amination protocol for pyrroles has been realized under phase transfer conditions using in situ generated chloramine as the electrophilic aminating agent [639].…”

Asymmetric Methods for Radical Addition to Imino Compounds

“…Although O-(mesitylenesulfonyl) hydroxylamine (MtsONH 2 ) was initially employed as the aminating reagent, its use is discouraged due to occasional uncontrolled exothermic decomposition during preparation and storage. Preferred reagents are O-(p-nitrobenzoyl)hydroxylamine (NbzONH 2 ), O-(diphenylphosphinyl)-hydroxylamine (Ph 2 P(¼O)ONH 2 ), and monochloramine (NH 2 Cl) [20]. Our optimized procedure for N-amination with NbzONH 2 entailed deprotonation with NaH (or KH) in hot dioxane, followed by introduction of NbzONH 2 as a solid at ambient temperature [21].…”

“…Several other halides, including methyl iodide and difunctional halides, were also effective (Table 2.6), with the exception of 2-chloroethyl addition, which gave low yield presumably due to radical fragmentation. Ethyl radical addition to nine additional hydrazones occurred in good yields (entries [12][13][14][15][16][17][18][19][20]. These adducts are epimeric to those derived from hydrazone 8a with respect to the new stereogenic center, as a result of simply changing the roles of the aldehyde and iodide precursors.…”

“…In this preparation, the oxazolidinone N-amination was accomplished using a solution of monochloramine in methyl tert-butyl ether [45], furnishing a quantitative yield of the N-amino-2-oxazolidinone, which in turn was condensed with methyl pyruvate to afford 62. Addition of ethyl iodide to (E)-62 using the Mn-mediated photolysis conditions as described above gave 66% yield of the ethyl adduct, with a modest diastereomer ratio of 70 : 30, while the corresponding isopropyl addition was very effective (85% yield, dr 92 : 8).…”