Oxidative N-nitration of secondary amines

Abstract

Reaction of secondary amines with the nitrite anion assisted by diacetoxyiodobenzene results in respective N nitroamines. It is the first example of oxidative nitration of the amino group. N Nitrosoamines are by products. The yields and the ratio of the nitration and nitrosa tion products depend on the nature of the starting amine, cation of the salt used, and the solvent.Reactions where the nitrite anion is a source of a cova lent nitro group are scarce. One of them is the oxidative nitration of primary and secondary C nitro compounds with the nitrite anion to gem dinitro compounds using Ag + or Fe +3 ions as oxidants. 1,2 The putative reaction mechanism involves the formation of intermediate A (Scheme 1). 2 Scheme 1The oxidant is a crucial reactant in the oxidative nitra tion. Compounds of hypervalent iodine have been widely used in organic synthesis as reactive and convenient oxi dizing agents over the last 25-30 years. 3,4 Combinations of aryliodo(III) derivatives (λ 3 iodanes) with such salts as NaN 3 5 or LiBr 6 resulting in oxidative functionalization of a CH bond were described in literature, but analogous combination λ 3 iodane/NaNO 2 has not been used as a nitrating reagent. Apparently, no example of the oxida tive nitration of the NH bond have been described so far.We demonstrated a possibility of nitration of the ami no group with nitrite salts and diacetoxyiodobenzene for the first time. The reaction occurs under neutral condi tions.It was shown that the reaction of secondary amines 1a-e with the nitrite anion in the presence of PhI(OAc) 2 (2), according to 1 H NMR data, gives the corresponding N nitroamines 3 in a yield of up to 40%, ~20-30% of N nitrosoamines 4 being also formed (Scheme 2). Scheme 2 R = Et (a), PhCH 2 (b), MeO 2 CCH 2 CH 2 (c), NCCH 2 CH 2 (d); R 2 N is morpholino (e); M = Na, K, Li, Et 4 N, Ag.The effect of the solvent, the nitrite salt cation, and the temperature regime of the reaction were studied by the example of bis(2 cyanoethyl)amine 1d. The choice of sol vents is interrelated with the choice of cations since apro tic solvents require salts with the appropriate solubility. By the example of [Et 4 N]NO 2 and LiNO 2 (Table 1) it was shown that in CH 2 Cl 2 , MeCN, or THF N nitrosoamine 4d prevailed in the reaction products, while MeOH changes this ratio in favor of N nitroamine 3d. The use of MeOH gives higher yields of N nitroamine 3d with other nitrite salts as well. Unlike the aprotic solvents, methanol no ticeably levels the influence of the cations, which later allowed using the most available NaNO 2 . The reaction in MeOH is weakly exothermic, the change in temperature from -20 °C to room temperature has little effect on the yield of products, the optimal reaction temperature is 0-5 °C.

Trimethyl Borate-Catalyzed, Solvent-Free Reductive Amination

“…The product was isolated in 84% yield (0.828 g, 4.2 mmol) as a colorless liquid after purification via column chromatography on silica gel using hexane/EtOAc (95:5) as an eluent. The spectral data matched with those reported in the literature …”

“…The spectral data matched with those reported in the literature. 36 1 H NMR (300 MHz, Chloroform-d) δ 7.42−7.25 (m, 10H), 3.85 (s, 4H), 2.09 (s, 1H). 13 C{1H} NMR (75 MHz, CDCl 3 ) δ 140.0, 128.4, 128.2, 127.0, 53.1.…”

Development of Scalable Routes to 1-Bicyclo[1.1.1]pentylpyrazoles

“…Alternatively, a de novo hydrazine synthesis was approached via N-amination of BCP amine 9 , which is accessible from 7 . N-Amination of aliphatic amines generally requires reactive and challenging-to-synthesize reagents such as oxaziridines or involves high-energy N–(NO) bond-containing intermediates . To address these challenges, N–N bond formation using O-substituted hydroxylamine reagents was attempted .…”

Formation of Complex Hydrazine Derivatives via Aza-Lossen Rearrangement

“…Indeed, functionalization of hydrazines is often challenging due to the toxicity, hazardous, and air sensitive character of many reagents. There is also an inherent chemoselectivity issue arising from the two reactive nucleophilic nitrogen atoms. , Additionally, the formation of N–N bonds often involves hazardous reactions (e.g., nitrosation or nitration) or a prefunctionalization to perform the cleavage of weak N–X bonds (where X = O, N, or Cl in the Raschig–Olin process) . Aza-Favorskii reactions of N-monosubstituted ureas was also reported to form hydrazine derivatives following ring opening of the diaziridone intermediate. , Many N–N bonds have been formed via dimerization, , but typically, the formation of heterodimers is difficult.…”