Synthesis of 6-Amino- and 6-Arylazoazulenes via Nucleophilic Aromatic Substitution and Their Reactivity and Properties

Abstract

The nucleophilic aromatic substitution (SNAr) reaction of diethyl 6-bromoazulene-1,3-dicarboxylate (1) with a variety of amines afforded the corresponding 6-aminoazulene derivatives 2a–2j in good-to-excellent yields. 6-Aminoazulene derivatives 3a–3f without the 1,3-diethoxycarbonyl functions were obtained by the deesterification of 2a–2f with 100% H3PO4. The reactivity of 6-aminoazulenes toward the bromination, SNAr, and palladium-catalyzed cross-coupling reactions was also clarified. 6-Arylazoazulenes 13a–13c were also prepared via the SNAr reaction of 1 with arylhydrazines, followed by oxidation with Pb­(OAc)4 in the presence of N2H4. The structural, optical, and electrochemical properties of the 6-amino- and 6-arylazoazulenes were revealed by single-crystal X-ray structure analysis, UV/vis spectroscopy, voltammetry analysis, spectroelectrochemistry, and theoretical calculations.

Alkynylazulenes as Building Blocks for Highly Unsaturated Scaffolds

“…Although the reaction of 2‐ethynyl‐ and 2‐phenylethynylazulenes with TCNE did not afford the corresponding TCBD derivative, since the 2‐azulenyl moiety is an unfavorable activating group toward the [2+2] CA‐RE reaction. Contrary to these results, compound 106 reacted with TCNE at room temperature to afford the corresponding TCBD derivative 334 in 94% yield, despite the deactivation of the alkyne moiety by the adjacent two electron‐withdrawing groups [68] . Generation of 334 in high yield under the mild condition should be attributed to the strong electron‐donating property of the pyrrolidinyl group at the 6‐position that enhances the reactivity of the alkyne moiety of 106 (Figure 55).…”

“…Although Sonogashira‐Hagihara cross‐coupling of 105 , obtained upon treatment of diethyl 6‐(pyrrolidin‐1‐yl)azulene‐1,3‐dicarboxylate 104 , with ethynylbenzene in the presence of 3 mol% Pd‐catalyst and 10 mol % CuI produced the cross‐coupling product 106 in low yield (12%) along with the recovery of 105 (85%), the use of excess CuI (50 mol %) has shown a significant improvement of the yield of 106 (89%) (Scheme 22). These results suggest the coordination of CuI to the pyrrolidine moiety in 105 that leads to a decrease in the activity of the Cu‐catalyst because 2‐haloazulenes without the 6‐amino substituent give the products in good‐to‐excellent yields in the presence of catalytic amount of CuI [68] …”

“…These results suggest the coordination of CuI to the pyrrolidine moiety in 105 that leads to a decrease in the activity of the Cu-catalyst because 2-haloazulenes without the 6-amino substituent give the products in good-to-excellent yields in the presence of catalytic amount of CuI. [68] Scheme 44. Synthesis of (1,4-phenylenebis(buta-1,3-diyne-4,1-diyl))bis(azulene) 205.…”

Development of Heterocycle-Substituted and Fused Azulenes in the Last Decade (2010–2020)

“…Similar to the aforementioned reaction, the reaction of 6-bromoazulene 146 with two ester groups with amines yields the corresponding 6-aminoazulene derivatives 147 in good to excellent yields ( Scheme 49 ) [ 68 , 69 ]. The electrophilic substitution reaction of a derivative with a pyrrolidine substituent at the 6-position with bromine provides 2-bromo-6-pyrrolidinylazulene derivative 148 .…”

Copper-Catalyzed Electrophilic Amination of Diarylcadmium Reagents Utilizing Acetone O-(4- chlorophenylsulphonyl)oxime and Acetone O-(2-naphthylsulphonyl)oxime as Amination Agent

“…Transition-metal-catalyzed C-N bond-forming is one of the most considerable scaffold transformations in organic synthesis for the various aryl amines. For these reasons, various procedures have been evolved for aryl C-N bond formation, for example, the reduction of aromatic nitro compounds (Jayapal et al, 2018), nucleophilic aromatic substitution (Shoji et al, 2019), Ullmann Reaction (Ullmann, 1903;Wang et al, 2019), Buchwald-Hartwig method (Snieckus and Kölmel, 2019), Chan-Lam coupling (Campbell Brewer, 2019) (Figure 1). The investigated methods relating to aryl amines let obtaining amines in good yields, but these methods have significant drawbacks, which are a high temperature, long reaction condition, high pressure, expensive or specific catalysts, and ligands.…”