1,2-Bis(4-(1,3-dioxolan-2-yl)phenyl)diazene Oxide Oxide

: A simple approach to synthesizing 1,2-bis(4-(1,3-dioxolan-2-yl)phenyl)diazene oxide was developed in this study, based on glucose as an eco-friendly reductant. Abstract: A simple approach to synthesizing 1,2-bis(4-(1,3-dioxolan-2-yl)phenyl)diazene developed in this study, based on glucose as an eco-friendly reductant.


Introduction
Azoxybenzenes are widely used as liquid crystals [1,2], natural and synthetic compounds with various biological activities (insecticidal activity, plant growth stimulators) [3][4][5][6] (Figure 1), ligands for preparing coordination polymers [7], and polyvinyl chloride stabilizers [8]. The reactivity of the azoxy group allows them to be used as building blocks in fine organic synthesis [9][10][11]. The main methods for synthesizing azoxybenzenes are the oxidation of aromatic amines [12,13] and azo compounds [14], and the reduction of nitroso compounds [15]. The reduction of nitro compounds is the most widely used method. The classic version uses sodium arsenite [16], sodium alkoxides [17], alkali metal borohydrides [18][19][20], Zn-BiCl3   The main methods for synthesizing azoxybenzenes are the oxidation of aromatic amines [12,13] and azo compounds [14], and the reduction of nitroso compounds [15]. The reduction of nitro compounds is the most widely used method. The classic version uses sodium arsenite [16], sodium alkoxides [17], alkali metal borohydrides [18][19][20], Zn-BiCl 3 [21], and Zn/NH 4 Cl in a mixture with 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF 4 ]) and water [22], or selective catalytic hydrogenation [23,24]. This method cannot be employed for substrates containing other functional groups that are sensitive to reduction. For instance, when reducing nitroaromatic aldehydes or ketones, the carbonyl group is simultaneously reduced [25][26][27][28]. In addition, the reaction is often accompanied by the formation of significant amounts of azo compounds, which complicates the isolation of pure azoxy compounds. In this case, azoxybenzenes with carbonyl groups can be used as starting compounds for the synthesis of analogs of natural and synthetic azoxymycins and other practically useful compounds, such as cyclic acetal prepared from 1,2-bis(4-formylphenyl)diazenoxide and ethylene glycol, which are able to stimulate the growth of grain crops [6].
Molbank 2021, 2021, x FOR PEER REVIEW 2 of 6 [21], and Zn/NH4Cl in a mixture with 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF4]) and water [22], or selective catalytic hydrogenation [23,24]. This method cannot be employed for substrates containing other functional groups that are sensitive to reduction. For instance, when reducing nitroaromatic aldehydes or ketones, the carbonyl group is simultaneously reduced [25][26][27][28]. In addition, the reaction is often accompanied by the formation of significant amounts of azo compounds, which complicates the isolation of pure azoxy compounds. In this case, azoxybenzenes with carbonyl groups can be used as starting compounds for the synthesis of analogs of natural and synthetic azoxymycins and other practically useful compounds, such as cyclic acetal prepared from 1,2-bis(4-formylphenyl)diazenoxide and ethylene glycol, which are able to stimulate the growth of grain crops [6]. We are interested in synthesizing 1,2-bis(4-(1,3-dioxolan-2-yl)phenyl)diazene oxide by reducing 2-(4-nitrophenyl)-1,3-dioxolane, using glucose as an eco-friendly reductant in alkaline medium. The reduction of nitro compounds under the action of glucose has been previously described [29]; however, despite its simplicity, the method is not widely used. In addition, in some cases, depending on the conditions of the reduction, the reaction products can be both aromatic amines [30] and azo compounds [31]. The reduction of 2-(4-nitrophenyl)-1,3-dioxolane under Li[AlH4] is accompanied by the formation of azo compounds [32].

Results and Discussion
To begin, 2-(4-nitrophenyl)-1,3-dioxolane 3 was synthesized from commercial 4-nitrobenzaldehyde 1 via acetalization with ethylene glycol 2 in a toluene medium (Scheme 1) [33]. Its physical constants and spectral data are in agreement with the literature data. [33]. The reduction of 2-(4-nitrophenyl)-1,3-dioxolane 3 was carried out by mixing it with ethanol in a 30% NaOH solution at 50 °C, along with a solution of 200 mol% glucose. Monitoring of the reaction by analytical thin-layer chromatography (TLC) showed that complete conversion is achieved after 2 h of stirring the reaction mixture at 50 °C (Scheme 2). We found that conducting experiments in a water-ethanol medium is optimal for carrying out the reduction, since it provides the highest yield of the desired product 4 and minimizes undesirable reactions and the resinification of the reaction mixture. Exchange of ethanol for iso-propanol or tetrahydrofuran leads to the partial destruction of the starting compound 3; it thus incompletely converts, and the yield of the desired product is The reduction of 2-(4-nitrophenyl)-1,3-dioxolane 3 was carried out by mixing it with ethanol in a 30% NaOH solution at 50 • C, along with a solution of 200 mol% glucose. Monitoring of the reaction by analytical thin-layer chromatography (TLC) showed that complete conversion is achieved after 2 h of stirring the reaction mixture at 50 • C (Scheme 2). [21], and Zn/NH4Cl in a mixture with 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF4]) and water [22], or selective catalytic hydrogenation [23,24]. This method cannot be employed for substrates containing other functional groups that are sensitive to reduction. For instance, when reducing nitroaromatic aldehydes or ketones, the carbonyl group is simultaneously reduced [25][26][27][28]. In addition, the reaction is often accompanied by the formation of significant amounts of azo compounds, which complicates the isolation of pure azoxy compounds. In this case, azoxybenzenes with carbonyl groups can be used as starting compounds for the synthesis of analogs of natural and synthetic azoxymycins and other practically useful compounds, such as cyclic acetal prepared from 1,2-bis(4-formylphenyl)diazenoxide and ethylene glycol, which are able to stimulate the growth of grain crops [6].

Results and Discussion
To begin, 2-(4-nitrophenyl)-1,3-dioxolane 3 was synthesized from commercial 4-nitrobenzaldehyde 1 via acetalization with ethylene glycol 2 in a toluene medium (Scheme 1) [33]. Its physical constants and spectral data are in agreement with the literature data. [33]. We found that conducting experiments in a water-ethanol medium is optimal for carrying out the reduction, since it provides the highest yield of the desired product 4 and minimizes undesirable reactions and the resinification of the reaction mixture. Exchange of ethanol for iso-propanol or tetrahydrofuran leads to the partial destruction of the starting compound 3; it thus incompletely converts, and the yield of the desired product is Scheme 2. Synthesis of azoxybenzene 4 from 2-(4-nitrophenyl)-1,3-dioxolane 3.
We found that conducting experiments in a water-ethanol medium is optimal for carrying out the reduction, since it provides the highest yield of the desired product 4 and minimizes undesirable reactions and the resinification of the reaction mixture. Exchange of ethanol for iso-propanol or tetrahydrofuran leads to the partial destruction of the starting compound 3; it thus incompletely converts, and the yield of the desired product is sharply reduced. When the reaction is carried out at the boiling point, the target compound is contaminated with resinous impurities that are difficult to separate. For complete conversion of the starting compound at room temperature, a time of more than 36 h is necessary; therefore, the reaction was carried out at 50 • C.
The target azoxybenzene 4 was purified by recrystallization from ethanol. The structure of 1,2-bis(4-(1,3-dioxolan-2-yl)phenyl)diazene oxide 4 was unambiguously confirmed by single-crystal X-ray analysis (Figure 2). sharply reduced. When the reaction is carried out at the boiling point, the target compound is contaminated with resinous impurities that are difficult to separate. For complete conversion of the starting compound at room temperature, a time of more than 36 h is necessary; therefore, the reaction was carried out at 50 °C.
plete conversion of the starting compound at room temperature, a time of more than 36 h is necessary; therefore, the reaction was carried out at 50 °C.

1,2-Bis(4-(1,3-dioxolan-2-yl)phenyl)diazene Oxide (4)
To 6 mL of ethanol, 7.5 mL of a 30% aqueous solution of sodium hydroxide and 0.5 g (2.56 mmol) of 2-(4-nitrophenyl)-1,3-dioxolane 3 were added. The reaction mixture was maintained at 50 • C, and a solution of 1 g (5.12 mmol) of glucose monohydrate in 1 mL of water was added, which was then stirred for 2 h at the specified temperature. Then, the reaction mixture was cooled and diluted with 50 mL of 2M hydrochloric acid, and the formed precipitate was filtered and washed on the filter with distilled water. The resulting residue was purified via recrystallization from EtOH, yielding azoxybenzene 4. Yield

Funding:
The research was carried out with the financial support of the Kuban Science Foundation in the framework of the scientific project maintained at 50 °C, and a solution of 1 g (5.12 mmol) of glucose monohydrate in 1 mL of water was added, which was then stirred for 2 h at the specified temperature. Then, the reaction mixture was cooled and diluted with 50 mL of 2M hydrochloric acid, and the formed precipitate was filtered and washed on the filter with distilled water. The resulting residue was purified via recrystallization from EtOH, yielding azoxybenzene 4. Yield 0.