Two new mild oxidizing agents 1,1,3,3-tetramethylguanidinium fluorochromate (TMGFC) and 1,1,3,3-tetramethylguanidinium chlorochromate (TMGCC) were prepared in high yields by reacting tetramethylguanidine with CrO3 and related acid. These reagents are suitable to oxidize various primary and secondary alcohols and oximes to the corresponding carbonyl compounds under solvent-free conditions and microwave irradiation.
Oxidation of various organic compounds under mild conditions is of great importance in synthetic organic chemistry [
Recently considerable attention has been paid to solvent-free reactions [
In continuation of our ongoing research program for developing newer chromium reagents [
All reagents and solvents were obtained from Aldrich and used without further purification. The 1H NMR spectrum was recorded on a Bruker Avance 300-MHz spectrometer (Germany). Elemental analysis was performed using an Elemental Micro Vario CHNS. Electrothermal melting points were determined by a 9200 digital melting point apparatus (United Kingdom) and are uncorrected. IR spectra were recorded on a Mathson 1000 FT-IR spectrometer. All microwave irradiation reactions were carried out on a Milestone Micro-Synth apparatus.
Chromium(IV)oxide (CrO3) (20 mmol, 2 g) was taken in a polyethylene beaker and 48% hydrofluoric acid (HF) (23 mmol, 1.1 mL) was added dropwise with continuous stirring for 10 min. The orange solution thus obtained was cooled in an ice-bath. To this solution 1,1,3,3-tetramethylguanidine (20 mmol, 2.5 mL) was added portion-wise in 15 min. The mixture was kept at −10°C for 1 hour. The orange amorphous solid thus formed was filtered off, washed twice with hexane, and dried under vacuum for 1 h. Yield: 85%, mp: 130-131°C; 1H NMR (300 MHz, DMSO-d6):
Chromium(IV)oxide (CrO3) (20 mmol, 2 g) was taken in a polyethylene beaker and 6 M hydrochloric acid (HCl) (20 mmol, 3.6 mL) was added dropwise with continuous stirring for 10 min. The orange solution thus obtained was cooled in an ice-bath. To this solution 1,1,3,3-tetramethylguanidine (20 mmol, 2.5 mL) was added portion-wise in 15 min. The mixture was kept at −10°C for 1 hour. The orange amorphous solid thus formed was filtered off, washed twice with hexane, and dried under vacuum for 1 h. Yield: 75%, mp: 136-137°C; 1H NMR (300 MHz, DMSO-d6):
The oxidant (1.5–2 mmol) was added to the substrate (1 mmol) in a mortar. Starting materials were instantly mixed, ground, and kept for the appropriate period at room temperature or in an oven without any further agitation. The progress of the reaction was monitored by using TLC on silica gel (benzene : ethyl acetate = 9 : 1). Upon completion of the reaction, extraction with ether (3 × 25 mL) and evaporation of the solvent gave the corresponding carbonyl compounds.
The substrate (1 mmol) and 1.5–2 mmol oxidant were mixed. To this mixture 0.5 mL CH2Cl2 was added. The mixture was subjected to microwave irradiation (1000 W). Upon completion of the reaction, extraction with ether (3 × 25 mL) and evaporation of the solvent gave the corresponding carbonyl compounds. The products formed were analyzed by their 2,4-dinitrophenylhydrazone derivatives. The precipitated 2,4-DNP was filtered off, weighed, and recrystallized from ethanol.
1,1,3,3-Tetramethylguanidinium fluorochromate (TMGFC) and 1,1,3,3-tetramethylguanidinium chlorochromate (TMGCC) can easily be prepared in good yields by reacting tetramethylguanidine with CrO3 and related acid at a molar ratio of 1 : 1 : 1 in aqueous medium.
TMGFC and TMGCC are orange colored stable amorphous solids at room temperature. They are moisture insensitive and can be stored in polyethylene containers for long periods without decomposition.
The pH values of 0.01 M aqueous solutions of PCC, PFC, TMGFC, and TMGCC were found to be 1.75, 2.45, 3.79, and 3.89. The higher pH values of TMGFC and TMGCC compared to their companion reagents attest to their far less pronounced acidic characters. So, TMGFC and TMGCC may be proper oxidizing agents for the oxidation of acid-sensitive compounds.
TMGFC and TMGCC are highly soluble in DMF and DMSO; slightly soluble in acetonitrile and dichloromethane; and insoluble in benzene, ether, chloroform, and toluene. These results are indicative of the ionic nature of the reagents.
The conductivity values of 10−3 M solutions of TMGFC and TMGCC in acetonitrile at 25°C were found as 140 Ω−1cm2mol−1 and 150 Ω−1cm2mol−1, respectively. So, they are 1 : 1 electrolytes.
The effect of substrate : oxidant molar ratios has been investigated by applying 1 : 1, 1 : 1.25, 1 : 1.5, and 1 : 2 molar ratios, respectively, for the oxidation of benzyl alcohol as a model substrate under solvent-free conditions at room temperature for 30 min. The yields thus obtained were given in Table
Oxidation of benzyl alcohol with different amounts of TMGCC and TMGFC.
Oxidants | Substrate : oxidants (molar ratio) | Yield |
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TMGCC | 1 : 1 | 72 |
1 : 1.25 | 74 | |
1 : 1.5 | 80 | |
1 : 2 | 86 | |
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TMGFC | 1 : 1 | 75 |
1 : 1.25 | 78 | |
1 : 1.5 | 85 | |
1 : 2 | 90 |
To show the influence of nature of solvent on the reactivity of the oxidants, various solvents such as CH2Cl2, acetone, and DMF have been used for the oxidation of benzyl alcohol as representative substrate (Table
Oxidation of benzyl alcohol in different solvents with TMGCC and TMGFC.
Solvents | Substrate : oxidation (molar ratio) | Reaction period/h | TMGCC Yield |
TMGFC Yield |
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CH2Cl2 | 1 : 2 | 2 | 82 | 88 |
Acetone | 1 : 2 | 2 | 63 | 70 |
DMF | 1 : 2 | 2 | 60 | 65 |
The use of more polar solvents such as DMF and acetone resulted in moderate yields.
In order to ascertain the efficiency of the reagents as oxidants, different types of primary and secondary alcohols and oximes were treated with the reagents by taking the molar ratio of substrate : oxidant as 1 : 1-2 under solvent-free conditions at room temperature and under microwave irradiation to afford the corresponding carbonyl compounds (Scheme
A probable mechanism for the oxidation with TMGCC and TMGFC is given on the basis of previously reported mechanisms [
Primary benzylic alcohols and 1-octanol were converted into their corresponding aldehydes with good to high yields (Tables
The oxidation of alcohols and oximes with TMGFC under solvent-free conditions at room temperature and under microwave irradiation.
Entry | Substrate | Product | Yield% (time) | |
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Solvent-free (hour) | Microwave (second) | |||
1 | CH3(CH2)6CH2OH | CH3(CH2)6CHO | 76 (4) | 77 (10) |
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2 |
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70 (4) | 75 (13) |
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3 |
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75 (3.5) | 76 (13) |
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4 |
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70 (4) | 75 (10) |
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5 |
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85 (0.5) | 90 (5) |
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6 |
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90 (0.5) | 92 (4) |
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7 |
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90 (1) | 93 (7) |
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8 |
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85 (1) | 89 (8) |
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9 |
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86 (1) | 92 (9) |
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10 |
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87 (1.25) | 88 (10) |
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11 |
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42 (4.5) |
60 (10) |
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12 |
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85 (1) | 85 (8) |
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13 | Benzoin oxime | Benzoin | 55 (8) | 58 (10) |
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14 | Cyclohexanone oxime | Cyclohexanone | 70 (4) | 75 (20) |
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15 | Cyclopentanone oxime | Cyclopentanone | 70 (7) | 78 (10) |
The oxidation of alcohols and oximes with TMGCC under solvent-free conditions at room temperature and under microwave irradiation.
Entry | Substrate | Product | Yield% (time) | |
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Solvent-free (hour) | Microwave (second) | |||
1 | CH3(CH2)6CH2OH | CH3(CH2)6CHO | 70 (4.5) | 74 (11) |
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2 |
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75 (4) | 75 (15) |
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3 |
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75 (3.5) | 73 (14) |
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4 |
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72 (5) | 73 (10) |
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5 |
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85 (1) | 87 (8) |
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6 |
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85 (1) | 90 (7) |
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7 |
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91 (1) | 89 (8) |
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8 |
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80 (2) | 85 (11) |
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9 |
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85 (1.5) | 84 (10) |
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10 |
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86 (1.5) | 85 (11) |
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11 |
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40 (6) |
50 (10) |
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12 |
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82 (1) | 86 (10) |
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13 | Benzoin oxime | Benzoin | 50 (9) | 54 (10) |
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14 | Cyclohexanone oxime | Cyclohexanone | 71 (4.5) | 74 (22) |
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15 | Cyclopentanone oxime | Cyclopentanone | 72 (8.5) | 72 (10) |
Aliphatic oximes such as cyclohexanone oxime and cyclopentanone oxime were deoximated more efficiently than benzoin oxime (Tables
During the reactions, the color of the oxidants changes from orange to brown, providing visual means for ascertaining the progress of the oxidation.
In order to show the oxidative ability of the reagents (TMGCC and TMGFC), we compared some of our results with those of PCC [
Comparison of oxidation of various organic substrates by TMGCC, TMGFC, PCC, PFC, BAAOC, and DmpzHFC.
Yield% (time [min]) | ||||||
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Substrate | TMGCC | TMGFCC | PCC [ |
PFC [ |
BAAOC [ |
DmpzHFC [ |
4-Methoxybenzyl alcohol | 91 (1) | 90 (1) | 94 (5) | 89 (10) | 99 (2) | 92 (2) |
4-Chlorobenzyl alcohol | 85 (1.5) | 86 (1) | 93 (10) | 78 (10) | 95 (7) | — |
Benzyl alcohol | 85 (1) | 90 (0.5) | 96 (15) | 93 (10) | 98 (1) | 85 (1) |
Cinnamyl alcohol | 85 (1) | 85 (0.5) | 95 (15) | 85 (10) | 85 (20) | 89 (2) |
In conclusion, we have developed two new reagents TMGFC and TMGCC for the oxidation of alcohols and oximes. We described a solvent-free and a highly efficient microwave induced procedure for the rapid synthesis of aldehydes and ketones. These transformations enjoy the chemical and environmental advantages of solvent-free reactions. The results obtained are satisfactory and show the new reagents to be valuable additions to the existing agent.
The authors declare that they have no competing interests.