A Direct Method for the Efﬁcient Synthesis of Hydroxyalkyl-Containing Azoxybenzenes A Direct Method for the Efficient Synthesis of Hydroxyalkyl-Containing Azoxybenzenes

: Reaction of nitrobenzyl alcohol with glucose (200 mol%) in the presence of NaOH in water-ethanol medium gave 1,2-bis(4-(hydroxymethyl)phenyl)diazene oxide, 1,2-bis(2-(hydroxymethyl) phenyl)diazene oxide and 1,2-bis(4-(1-hydroxyethyl)phenyl)diazene oxide in 76%, 76% and 72% yields, respectively. Abstract: Reaction of nitrobenzyl alcohol with glucose (200 mol%) in the presence of NaOH in water-ethanol medium gave 1,2-bis(4-(hydroxymethyl)phenyl)diazene oxide, 1,2-bis(2-(hydroxymethyl)phenyl)diazene oxide and 1,2-bis(4-(1-hydroxyethyl)phenyl)diazene oxide in 76%, 76% and 72% yields, respectively.


Results and Discussion
Various nitroaryl-containing benzyl alcohols 2 (commercially available or easy synthesizable by known methods in high yields [31][32][33]) can serve as convenient starting compounds for the synthesis of hydroxyalkyl-containing azoxybenzenes. Similar to 2-(4-nitrophenyl)-1,3-dioxolane [24], the reduction of nitrobenzyl alcohols 2 readily proceeds on exposure to glucose (200 mol%) in the presence of sodium hydroxide in the water-ethanol medium. The TLC or GC/MS control of the reaction course shows that complete conversion of the substrate occurs within 30 min of keeping the reaction mixture at 50 • C and vigorous stirring (Scheme 2). 2022, 2022, x FOR PEER REVIEW 2 of 5

Results and Discussion
Various nitroaryl-containing benzyl alcohols 2 (commercially available or easy synthesizable by known methods in high yields [31][32][33]) can serve as convenient starting compounds for the synthesis of hydroxyalkyl-containing azoxybenzenes.
Similar to 2-(4-nitrophenyl)-1,3-dioxolane [24], the reduction of nitrobenzyl alcohols 2 readily proceeds on exposure to glucose (200 mol%) in the presence of sodium hydroxide in the water-ethanol medium. The TLC or GC/MS control of the reaction course shows that complete conversion of the substrate occurs within 30 min of keeping the reaction mixture at 50 °C and vigorous stirring (Scheme 2). The target products 3 precipitate as a crystalline solid after dilution of the reaction mass with water. Products were filtered off, washed with water, and further purified by recrystallization or flash chromatography.
The structure of 3 was confirmed by 1 H and 13 C NMR spectroscopy, IR spectroscopy, and high-resolution mass spectrometry.
In this case, successful reduction to azoxy derivatives was due to a combination of experimental conditions, namely the reaction time, reaction medium and lack of aeration. It is also known that the reduction of nitroarenes by glucose can be carried out to obtain azo compounds [34][35][36] and aromatic amines [37].

Materials and Methods
The reactions were monitored by thin-layer chromatography (Sorbfil, Imid Ltd., Krasnodar, Russia). The 1 H-NMR, 13 C-NMR spectra were acquired on ECA400 (JEOL) (400 and 100 MHz, respectively) spectrometers in (CD3)2SO at room temperature. The chemical shifts δ were measured in ppm with reference to the residual solvent resonances

General Procedure for the Preparation of Hydroxyalkyl-Containing Azoxybenzenes (3)
Nitrobenzyl alcohol 2 (3.26 mmol) in ethanol (6 mL) was added to 30% aq. NaOH (7.5 mL). At 50 °C, a solution of glucose monohydrate (1.29 g, 6.5 mmol) in water (1 mL) was added. The mixture was stirred for 30 min at 50 °C. The reaction was cooled, diluted The target products 3 precipitate as a crystalline solid after dilution of the reaction mass with water. Products were filtered off, washed with water, and further purified by recrystallization or flash chromatography.
The structure of 3 was confirmed by 1 H and 13 C-NMR spectroscopy, IR spectroscopy, and high-resolution mass spectrometry.
In this case, successful reduction to azoxy derivatives was due to a combination of experimental conditions, namely the reaction time, reaction medium and lack of aeration. It is also known that the reduction of nitroarenes by glucose can be carried out to obtain azo compounds [34][35][36] and aromatic amines [37].

Materials and Methods
The reactions were monitored by thin-layer chromatography (Sorbfil, Imid Ltd., Krasnodar, Russia). The 1 H-NMR, 13 C-NMR spectra were acquired on ECA400 (JEOL) (400 and 100 MHz, respectively) spectrometers in (CD 3 ) 2 SO at room temperature. The chemical shifts δ were measured in ppm with reference to the residual solvent resonances

General Procedure for the Preparation of Hydroxyalkyl-Containing Azoxybenzenes (3)
Nitrobenzyl alcohol 2 (3.26 mmol) in ethanol (6 mL) was added to 30% aq. NaOH (7.5 mL). At 50 • C, a solution of glucose monohydrate (1.29 g, 6.5 mmol) in water (1 mL) was added. The mixture was stirred for 30 min at 50 • C. The reaction was cooled, diluted with water, and the formed precipitate was filtered and washed with distilled water. The resulting residue was purified via recrystallization from EtOH.  Figure S2). 13 Figure S12).

Supplementary Materials:
The following can be downloaded online. Figure S1: IR-spectrum of 3a; Figure S2: 1 H-NMR of 3a; Figure S3: 13 C-NMR of 3a; Figure S4: HRMS of 3a; Figure S5: IR-spectrum of 3b; Figure S6  Acknowledgments: The HRMS study was accomplished with the use of scientific equipment of the Collective Employment Centre "Ecoanalytical Centre", Kuban State University (A. Z. Temerdashev).

Conflicts of Interest:
The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.