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Document Type : Original Research Article

Authors

Department of Chemistry, Faculty of Science, University of Benghazi, Benghazi, Libya

10.22034/ajgc.2022.3.5

Abstract

A crossover Cannizaro reaction by using traditional and grinding techniques was used to convert aryl aldehydes into aryl alcohols. The condensation of several substituted aryl aldehydes with formaldehydes in the presence of potassium hydroxide permitted the aryl alcohols to be produced in a high yield without the use of any solvent. Elemental analysis, FT-IR, and 1H-NMR spectra were used to characterize the final products.

Graphical Abstract

Transformation of aryl aldehydes to alcohols by solvent-less ‎crossed cannizaro reaction

Keywords

Main Subjects

Introduction

Aryl alcohols were prepared by the Crossed Cannizaro reaction, a chemical reaction that involves the redox disproportionation of non-enolizable aldehydes in concentrated base to alcohols and carboxylic acids [13].

The Cannizzaro reaction was elevated in importance in organic synthesis due to its ability to produce high yield alcohol [4] when carried out in solvent reactions on various mineral oxide surfaces [5]. With a good product yield, the crossed Cannizaro reaction 6 with Yb(OTf)3 and in the presence of (CH3CH2)4N+OH- in intermolecular crossed Cannizaro [6, 7] reaction were used. State organic reactions have recently attracted great interest, in which many organic techniques are carried out in solvent-free conditions with higher yields, shorter times, and mild conditions [8]. At 100 °C, ruthenium-catalyzed transfer hydrogenation [9, 10], and microwave irradiation [11, 12] in the presence of KOH and NaOH. In this study, a solvent-free crossed Cannizzaro reaction was used that was carried out by using two comparable grinding techniques in a pestle mortar and a glass test tube heated in an oil bath. Aryl alcohols were prepared by the cross Cannizzaro reaction, in which substituted aryl aldehydes reacted with formaldehyde in the presence of KOH, where they underwent various chemical reactions to produce an aryl alcohol in higher yields. Aryl alcohols have been used as intermediates for the preparation of many organic compounds with therapeutic value [7, 8]. Numerous reviews reveal that aryl alcohol derivatives exhibit importance in pharmacological activities, such as potential cytotoxic agents, antimicrobial agents, antiviral, anti-inflammatory, anesthetic, etc. [9, 10].

The growing awareness of environmental effect of the chemical activities necessitates the development of novel technologies for the synthesis of chemical substances that are both environmentally benign and commercially feasible. Unlike traditional solution-based processes, mechanochemical green synthesis is an ecologically friendly approach that produces better yields of synthesized products while avoiding the use of harmful organic solvents. Because of these benefits, this novel technique for organic synthesis should be given further consideration because there is no organic solvent and no external heating, the solvent-free grinding approach offers numerous benefits over the traditional reflux method. Due to the heat generated during the grinding process, the side product water evaporates, preventing the backward reaction, and resulting in a greater yield.

Experimental

Materials and methods

Melting points were determined on Stuart apparatus and were uncorrected. IR spectra were recorded on an FT-IR Perkin-Elmer spectrophotometer by using KBr pellets for solids and neat for liquids on the Perkin Elmar 883 spectrometer. 1H-NMR spectra were recorded on a Bruker AC-300 MHz spectrometer with TMS as an internal reference and in CDCl3 solvent. Chemical shifts relative to TMS were reported in units as parts per million (ppm). Elemental analysis was carried out by Parkin-Elmer 240. Chemicals and solvents were of commercial reagent grade. Aryl alcohols were prepared from various aryl aldehydes by the cross-Cannizzaro reaction, as displayed in Scheme 1.

General procedure for synthesis of aryl alcohols (IIIa-f) by using the crossed cannizzaro reaction

A mixture of aryl benzaldehyde (Ia-f), formaldehyde (0.1 mmol), and KOH (2 mmol) was ground in a pestle mortar for 30 minutes, or the mixture was added to a glass test tube fitted with a condenser and heated in an oil bath at 100 °C for 30 minutes. The reaction progress was checked out through the thin layer chromatography until no aldehyde was presented in the reaction mixture. The whole reaction mixture was filtered by using water, and the precipitate (aryl alcohol) was collected on the filter paper, washed with water, and dried. The filtrate was acidified, and the obtained aryl acid precipitate was filtered and dried. Isolated alcohols were characterized by melting points, FT-IR, 1H-NMR, and mass spectrometry.

Scheme 1. Crossed cannizaro reaction of aryl aldehydes by using solid KOH

Compound IIIa

Yield: 96%, IR (KBr) (νmax/ cm-1): 3169 (OH, alcohol), 3032 (CH, sp2), 2874 (CH, sp3), 1602, 1496, and 1454 (Ar-C=C). 1H-NMR (300 MHz, CDCl3): δ 2.65 (s, 1H, OH), 4.70 (s, 2H, CH2), and 7.28-7.46 (m, 5H, Ar-H). Anal. Calc. for C7H8O (108.14): C, 77.75; H, 7.46; O, 14.80; found: C, 77.90; H, 7.85; O, 14.95%.

Compound IIIb

Yield: 86%, mp 34.5 °C, IR (KBr) (νmax/ cm-1): 3100-3700 (OH alcohol), 3023-3057 (CH sp2), 2883-2960(CH sp3), 1604, 1491 (Ar-C=C), 1380, and 1460 (CH2, CH3, bend). 1H-NMR (300 MHz, CDCl3): δ 1.95 (s, 1H, OH), 2.32 (s, 3H, Me), 4.63 (s, 2H, CH2), and 7.0-7.46 (m, 4H, Ar-H). Anal. Calc. for C8H10O (122.16): C, 78.65; H, 8.25; O, 13.10; found: C, 78.76; H, 8.04; O, 13.05%.

Compound IIIc

Yield: 85%, IR (KBr) (νmax/ cm-1): 3326 (OH alcohol), 3027 (CH, sp2), 2870-2921 (CH, sp3), 1666, 1489 (Ar-C=C), 1363, and 1457 (CH2, CH3, bend). 1H-NMR (300 MHz, CDCl3): δ 1.90 (s, 1H, OH), 2.34 (s, 3H, Me), 4.63 (s, 2H, CH2), 7.16 (d, 1H, Ar-H), 7.23 (s, 1H, Ar-H), 7.28 (m, 2H, Ar-H), and 7.48 (m, 1H, Ar-H). Anal. Calc. for C8H10O (122.16): C, 78.65; H, 8.25; O, 13.10; found: C, 78.77; H, 8.06; O, 13.03%.

Compound IIId

Yield: 83%, mp 58-60 °C, IR (KBr) (νmax/ cm-1): 3049-3371 (OH alcohol), 3006-3022 (CH, sp2), 2733-2922 (CH sp3), 1616, 1470 (Ar-C=C), 1381, and 1448 (CH2, CH3, bend). 1H-NMR (300 MHz, CDCl3): δ 1.88 (s, 1H, OH), 2.33 (s, 3H, Me), 4.57 (s, 2H, CH2), 7.14 (d, 2H, Ar-H), and 7.21 (d, 2H, Ar-H). Anal. Calc. for C8H10O (122.16): C, 78.65; H, 8.25; O, 13.10; found: C, 78.86; H, 8.06; O, 12.99%.

Compound IIIe

Yield: 87%, mp 74 °C, IR (KBr) (νmax/ cm-1): 3313 (Ar-OH), 3112 (CH, sp2), 2849-2940 (CH, sp3), 1580, 1613 (C=C, Ar), 1367 (NO2), 1482 (CH2, bend), and 1059 (C-OH). 1H-NMR (300 MHz, CDCl3): δ 2.53 (t, 1H, OH), 4.97 (d, 2H, CH2), 7.50 (t, 1H, Ar-H), 7.65 (td, 1H, Ar-H), 7.70 (d, 1H, Ar-H), and 8.12 (dd, 1H, Ar-H). Anal. Calc. for C7H7NO3 (153.14): C, 54.90; H, 4.61; O, 31.34; N, 9.16; found: C, 54.45; H, 4.90; O, 31.09; N, 9.04%. 

Compound IIIf

Yield: 90%, mp 30-31 °C, IR (KBr) (νmax/cm-1): 3352-3360 (Ar-OH), 3092 (CH, sp2), 2872-2931 (CH, sp3), 1628, 1684 (C=C, Ar), 1342, 1628 (NO2), 1442 (CH2, bend), and 1059 (C-OH). 1H-NMR (300 MHz, CDCl3): δ 1.90 (br, 1H, OH), 4.84 (d, 2H, CH2), 7.54 (t, 1H, Ar-H), 7.71 (dd, 1H, Ar-H), 8.16 (dd, 1H, Ar-H), and 8.26 (s, 1H, Ar-H). Anal. Calc. for C7H7NO3 (153.14): C, 54.90; H, 4.61; O, 31.34; N, 9.15; found: C, 54.34; H, 4.96; O, 31.09; N, 9.04%.    

Compound IIIg

Yield: 80%, mp 93 °C, IR (KBr) (νmax/cm-1): 3522 (Ar-OH), 3072, 3082 (CH, sp2), 2868-2922 (CH, sp3), 1512, 1603 (C=C, Ar), 1344, 1512 (NO2), 1460 (CH2, bend), and 1059 (C-OH). 1H-NMR (300 MHz, CDCl3): δ 2.41 (br, 1H, OH), 4.82 (d, 2H, CH2), 7.52 (t, 1H, Ar-H), and 8.18 (d, 2H, Ar-H). Anal. Calc. for C7H7NO3 (153.14): C, 54.90; H, 4.61; O, 31.34; N, 9.15; found: C, 54.98; H, 4.82; O, 31.05; N, 9.02%.

Compound IIIh

Yield: 60%, mp 82 °C, IR (KBr) (νmax/cm-1): 3420 (Ar-N), 3222 (Ar-OH), 3011-3040 (CH, sp2), 2868-2922 (CH sp3), 1585 (NH2 bend), and 1300 (C-O). 1H-NMR (300 MHz, CDCl3): δ 3.60 (s, 1H, OH), 4.54 (s, 2H, CH2), 3.55 (s, 2H, NH2), 6.62 (d, 1H, Ar-H), 6.64 (m, 1H, Ar-H), and 7.04-7.10 (m, 2H, Ar-H). Anal. Calc. for C7H9NO (123.15): C, 68.27; H, 7.37; O, 12.99; N, 11.37; found: C, 68.34; H, 7.48; O, 12.84; N, 11.22%.

Compound IIIi

Yield: 45%, mp 93-94 °C, IR (KBr) (νmax/cm-1): 3500 (Ar-N), 3200 (Ar-OH), 3011 (CH, sp2), 2922 (CH, sp3), 1590 (NH2 bend), and 1300 (C-O). 1H-NMR (300 MHz, CDCl3): δ 5.00 (s, 1H, OH), 4.35 (s, 2H, CH2), 4.90 (s, 2H, NH2), 6.40 (d, 1H, Ar-H), 6.52 (s, 1H, Ar-H), 6.44 (d, 2H, Ar-H), and 6.92 (m, 1H, Ar-H). Anal. Calc. for C7H9NO (123.15): C, 68.27; H, 7.37; O, 12.99; N, 11.37; found: C, 68.39; H, 7.42; O, 12.75; N, 11.27%.

Compound IIIj

Yield: 35%, mp 60-65 °C, IR (KBr) (νmax/ cm-1): 3365 (Ar-N), 3225 (Ar-OH), 3011-3040 (CH, sp2), 2930 (CH, sp3), 1585 (NH2, bend), and 1300 (C-O). 1H-NMR (300 MHz, CDCl3): δ 3.62 (s, 1H, OH), 4.65 (s, 2H, CH2), 6.24 (s, 2H, NH2), 6.55 (d, 2H, Ar-H), and 7.16 (d, 2H, Ar-H). Anal. Calc. for C7H9NO (123.15): C, 68.27; H, 7.37; O, 12.99; N, 11.37; found: C, 68.32; H, 7.34; O, 12.78; N, 11.29%.

Compound IIIk

Yield: 85%, mp 58-61 °C, IR (KBr) (νmax/cm-1): 3360 (OH alcohol), 3036-3064 (CH, sp2), 2836-2955 (CH, sp3), 1612, 1456 (Ar-C=C), 1393, 1464 (CH2, CH3, bend), and 1290 (C-O). 1H-NMR (300 MHz, CDCl3): δ 1.90 (s, 1H, OH), 3.75 (s, 3H, OMe), 4.60 (s, 2H, CH2), 6.82 (d, 1H, Ar-H), 6.90 (m, 2H, Ar-H), 7.23 (m, 1H, Ar-H), and 7.26 (d, 1H, Ar-H). Anal. Calc. for C8H10O2 (123.15): C, 69.54; H, 7.30; O, 23.16; found: C, 69.38; H, 7.32; O, 23.11%.

Compound IIIl

Yield: 88%, (KBr) (νmax/cm-1): 3365 (OH alcohol), 3036-3064 (CH, sp2), 2935-2836 (CH, sp3), 1603, 1490 (Ar-C=C), 1380, 1464 (CH2, CH3, bend), and 1260 (C-O). 1H-NMR (300 MHz, CDCl3): δ 1.87 (s, 1H, OH), 3.80 (s, 3H, OMe), 4.65 (s, 2H, CH2), 6.87 (d, 1H, Ar-H), 6.91 (d, 2H, Ar-H), and 7.26 (t, 1H, Ar-H). Anal. Calc. for C8H10O2 (123.15): C, 69.54; H, 7.30; O, 23.16; found: C, 69.34; H, 7.37; O, 23.21%.

Compound IIIm

Yield: 79%, mp 58-61 °C, IR (KBr) (νmax/ cm-1): 3420 (OH alcohol), 3006 (CH, sp2), 2852-2955 (CH, sp3), 1613, 1440 (Ar-C=C), 1380,1448 (CH2, CH3, bend), and 1249 (C-O). 1H-NMR (300 MHz, CDCl3): δ 1.85 (s, 1H, OH), 3.82 (s, 3H, OMe), 4.62 (s, 2H, CH2), 6.91 (d, 1H, Ar-H), and 7.30 (d, 2H, Ar-H). Anal. Calc. for C8H10O2 (138.16): C, 69.54; H, 7.30; O, 23.16; found: C, 69.31; H, 7.40; O, 23.26%.

Compound IIIn

Yield: 75%, mp 38-41 °C, IR (KBr) (νmax/cm-1): 3180 (OH alcohol), 3083 (CH, sp2), 2870 (CH, sp3), 2252 (CN), 1602, 1496, and 1454 (Ar-C=C). 1H-NMR (300 MHz, CDCl3): δ 2.60 (s, 1H, OH), 4.72 (s, 2H, CH2), 7.39-7.44 (m, 2H, Ar-H), and 7.55-7.60 (m, 2H, Ar-H). Anal. Calc. for C8H7NO (133.15): C, 72.15; H, 5.30; O, 12.02; N, 10.52; found: C, 72.31; H, 5.41; O, 12.21; N, 10.41%.

Results and Discussion

The effect of reaction conditions was studied by using 3-nitrobenzaldehyde (1 mmol) as a starting material, where a different molar ratio and reaction time were included in this experiment. When the molar ratio of the reaction ingredients (3-nitrobenzaldehyde/HCHO/KOH) was adjusted to a (1: 2: 0.5) ratio, the alcohol yield was 79%. On changing the molar ratio to (1: 2: 1), the yield increased to 85%. Further changing to (1: 2: 1.5) and to (1: 2: 2), increased the yield to 88% and 90%, respectively. Increasing the amount of formaldehyde to (1: 3: 2) and (1: 4: 2) ratios has no discernible effect. These results made it easier to know the best reaction conditions (Table 1).

The experiments were performed for the conversion of many aryl aldehydes into alcohols by the crossed cannizaro reaction adapting grinding technique and oil bath heating of the grinding reaction batches. In fact, the initial step in this reaction is equilibrium between the formaldehyde and hydroxide ion to form a tetrahedral intermediate, as depicted in Scheme 2. The formaldehyde carbonyl is extremely reactive and the equilibrium will go strongly to the side of the tetrahedral intermediate, leading to the achievement of a much higher yield of the desired alcohol.

Table 1. Effect of grinding reaction conditions on crossed cannizaro condensation of IIIe

Compound entry

Molar ratio

Reaction grinding time

Yield (%)

1

1: 2:0.5

19

79

2

1:2:1

18

85

3

1:2:1.5

20

94

4

1:2:2

20

96

5

1:3:2

21

94

6

1:4:2

21

94

7

1:5:2

19

95

8

1:5:1.5

20

93

We reported a facile free solvent conversation of various aryl aldehydes (Ia-n) into aryl alcohols (IIa-n) by using formaldehyde and KOH by using a grinding technique and heating the reaction batch in an oil bath between 100 °C and 110 °C, as presented in Scheme 1. After the reaction completion, as indicated by TLC, the reaction mixture was filtered and the precipitate of aryl alcohol was obtained, washed with water, and acidified. All synthesized compounds and the reactions were characterized and monitored by TLC, melting points, elemental analysis, FT-IR, and 1H-NMR. They all gave the satisfactory results. This solvent-free potassium hydrated crossed cannizzaro reaction demonstrated an efficient and simple eco-friendly method with high aryl alcohol yields.

Scheme 2. Crossed cannizaro reaction of aryl aldehydes by using solid KOH

Conclusion

When we consider that all reactions generated the needed materials with high products that may exceed 96 percent, the results of this research owing to the application of environmentally friendly technology and solvent free technology are considered as extremely satisfying results. These reactions can take place in the presence of solvents that are toxic to humans and the environment, and the result is often the same proportion of products. The collected materials were thoroughly evaluated by employing IR, 1H-NMR, and the elemental analysis indicating that the needed good had been obtained.

Acknowledgment

All thanks are extended to the Department of Chemistry at the University of Benghazi for the support and for providing the laboratory, equipment, tools, and chemicals required for this research.

Disclosure Statement

No potential conflict of interest was reported by the authors.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Authors' contributions

All authors contributed to data analysis, drafting, and revising of the paper and agreed to be responsible for all the aspects of this work.

How to cite this manuscript: Othman O. Dakhil*, Mohamed Gebriel Elarfi, Hussniyia A. Al-Difar. Transformation of aryl aldehydes to alcohols by solvent-less ‎‎crossed cannizaro reaction. Asian Journal of Green Chemistry, x(x) 2022, xx-xx.  DOI: 10.22034/ajgc.2022.3.5

[1]. Cannizzaro S. Ann. Chem., 1853, 88:129
[2]. Geissman T.A. Org. React., 1944‎‎,2:94 [Google Scholar], [Publisher]
[3]. List K., Limpricht H. Ann., 1854, 90:190
[Crossref], [Google Scholar], [Publisher]
[4]. C. Gardner S, Arnet L., William A., Charles
R.M. J. Am. Chem. Soc., 1979, 101:3576 [Crossref], [Publisher]
[5]. Varma R.S., Kabalka G.W., Evans L.T., Pagni R.M., Synth. Commun., 1985, 15:279 [Crossref], [Google Scholar], [Publisher]
[6]. Curini M., Epifano F., Genovese S., Marcotullio M.C., Rosati O. Org. Lett., 2005, 7:1331 [Crossref], [Google Scholar], [Publisher]
[7]. Akhigbe F., Ryppa C., Zeller M., Bruckner C. J. Org. Chem., 2009, 74:4927 [Crossref], [Google Scholar], [Publisher]
[8]. Yoshizawa K., Toyota S., Toda F., Tetrahedron Lett., 2001, 42:7983 [Crossref], [Google Scholar], [Publisher]
[9]. Vida Y., Perez-Inestrosa E., Suau R. Tetrahedron Lett., 2005, 46:1575
[10]. Motiur Rahman A.F.M., Kadi A.A., Arabian
Journal of Chemistry, 2016, 6:S1373 [Crossref], [Google Scholar], [Publisher]
[11]. Sharifi A., Mojtahedi M.M., Saidi M.R. Tetrahedron Lett., 1999, 40:1179 [Crossref], [Google Scholar], [Publisher]
[12]. Varma R.S., Naicker K.P., Liesen P.J. Tetrahedron. Lett., 1998, 39:8437