https://www.thevespiary.org/rhodium/Rhodium/chemistry/ketamine2.html (https://www.thevespiary.org/rhodium/Rhodium/chemistry/ketamine2.html)
), as well as the standard route (they are much the same)(https://www.thevespiary.org/rhodium/Rhodium/chemistry/pcp/ketamine.html (https://www.thevespiary.org/rhodium/Rhodium/chemistry/pcp/ketamine.html)
,https://www.thevespiary.org/rhodium/Rhodium/chemistry/ketamine.html (https://www.thevespiary.org/rhodium/Rhodium/chemistry/ketamine.html)
)Molecule: (https://www.the-hive.ws/forum/faq.pl?Cat=#applet)
very tasty ("Clc1ccccc1C(=O)C2(O)CCCC2")Molecule: (https://www.the-hive.ws/forum/faq.pl?Cat=#applet)
grignard ("Clc1ccccc1CCl.O=C2CCCC2>>Clc1ccccc1CC2(O)CCCC2")Molecule: (https://www.the-hive.ws/forum/faq.pl?Cat=#applet)
oxidize,KMnO4 ("Clc1ccccc1CC2(O)CCCC2>>Clc1ccccc1C(=O)C2(O)CCCC2")
KMnO4/CuSO4.5H2O
Equal weights of potassium permanganate and copper sulfate pentahydrate were ground together in a mortar. The resulting fine, highly colored product was then used as a heterogeneous oxidant in methylene chloride solutions.
time(h) yield
ethyl benzene --> acetophenone 70 95%
propyl benzene --> ethyl phenyl ketone 70 90%
butyl benzene --> propyl phenyl ketone 72 88%
indane --> indanone 72 78%
...
cumene --> 2-phenyl 2-propanol (70?) 78%
sec-butylbenzene--> 2-phenyl 2-butanol (140?) 79%
...
Oxidation of Isochroman:
0.188 g / 1.4 mmol dissolved in 20 mL DCM with 3.2 g oxidant were placed in 50 mL RBF and refluxed gently. After 72 h, the product was filtered through a Celite pad and the residue washed successively with DCM (3 x 20 mL) and ether (ditto). Evaporation gave the lactone, 2-chromanone (0.198 g, 1.35 mmol, 96%).
A good proof of concept, BUT, too big excess of permanganate and TOO SLOW! This is solved by PTC, as we shall see in the next few papers.
Note the oxidation of cumene to a tertiary alcohol. This is what I'm talking about!
Synthetic Communications 2003, 1057 : Ion exchange catalysis in oxidation of organic compounds with KMnO4
Oxidation of Indan with KMnO4/IER:
Indan (0.118 g, 1 mmol) was dissolved in 30 mL DCM and placed in a RBF with mag stirring. Finely ground KMnO4 (1 g) and Ion Exchange Resin (1 g) were added and the mixture stirred at reflux, monitored by TLC. After 7 h, reaction was complete. Product was filtered through sintered glass and the residue washed with 20 mL DCM and evaporated to give 0.93 mmol, 93% of indanone.
time(h) yield
ethyl benzene --> acetophenone 5.5 91%
propyl benzene --> ethyl phenyl ketone 5.8 93%
butyl benzene --> propyl phenyl ketone 5.8 92%
tetralin --> tetralone 7 95%
indane --> indanone 7 93%
...
toluene --> benzoic acid 3 90%
They also oxidize a lot of other stuff, i.e. alcohols, sulfides, thiols, etc. Note the improved reaction time. Still not on a good scale yet, though.
J. Chem. Research (Synopses) 2000, 38 : Cation exchange resin supported oxidation of alkylbenzenes and olefins using potassium permanganate
Typical procedure for oxidation of alkylbenzenes:
KMnO4 (0.948 g, 6 mmol) is added to a suspension of Tulsion T-40 resin (2 g), t-butyl alcohol (4 ml) <<note--it's oxidation proof. Try acetone or MEK as well>>, water (1 ml), tetralin (246 mg, 2 mmol) in DCM (20 ml) in lots during 10 min time. The reaction mixture was stirred at room temp for 4 h, filtered and dried over anhydrous Na2SO4. After removing the solvent, the product obtained is purified by column chromatography to get a-tetralone (263 mg, 90%)
time(h) yield
ethyl benzene --> acetophenone 4.5 86%
tetralin --> tetralone 4 90%
isobutylbenzene --> Isopropyl phenyl ketone 5 88%
cumene --> 2-phenyl 2-propanol 4 82%
...
Note that in this paper, they are only using a 3-times excess of KMnO4. Still, the scale isn't BIG enough!! ::)
Synthesis 1989, 293 : A convenient oxidation of benzylic methyl, methylene, and methine groups with potassium permanganate/triethylamine reagent
KMnO4 (1.58 g, 5 mmol) and Et3N (506 mg, 5 mmol) are first mixed in a RBF, followed by addition of water (1 ml) and CHCl3 (20 ml) or 1,2-dichloropropane under magnetic stirring. The permanganate color fades and the mixture turns into a brick color with a gentle evolution of heat within 3 minutes. After addition of the substrate (5 mmol), 3 mL of 6 M H2SO4 is added dropwise. Oxidation proceeds immediately at 20 C as acid is introduced, and is completed after an additional stirring for 30 to 90 minutes at RT, as indicated by TLC. The mixture remains homogeneous during the reaction. 30 ml CHCl3 is then added to the mixture and the coloidal MnO2 is filtered with the aid of silica gel (5 g) and CaCl2 (1 g, also acts as drying agent). This operation also provides considerable purification, and concentration of the filtrate on a rotary evaporator usually leads to pure product.
For tertiary benzylic alcohols like triphenylmethane and 2-phenylpropane, a 2:1 ratio of KMnO4 to substrate is used because they are less reactive.
time(h) yield
ethyl benzene --> acetophenone 58%
tetralin --> tetralone 4 84%
triphenylmethane--> triphenylmethanol 5 46%
cumene --> 2-phenyl 2-propanol 4 61%
...
Yield not so good, but it shows that alternate methods are possible.
Their method works better for diaryl methylene groups.
Now, for some real fun--complex functionalized compounds!
Tetrahedron 2003, 1309 : Page 1314
Preparation of 8-acetylamino-4-(2,2-dimethyl-1,1-diphenyl-silapropoxy)-6-fluoro-5-methyl-1-one-2,3,4-tetrahydronaphthalene: <<where do I get the idea they used autonom to name this?>>Molecule: (https://www.the-hive.ws/forum/faq.pl?Cat=#applet)
damn man, I can't read that! ("c1ccccc1[Si](c2ccccc2)(C(C)(C)C)OC3CCCc4c3c(C)c(F)cc4NC(=O)C>>c1ccccc1[Si](c2ccccc2)(C(C)(C)C)OC3CCC(=O)c4c3c(C)c(F)cc4NC(=O)C")
To a solution of (the former) (0.13 g, 0.27 mmol) in 6.4 mL acetone and 0.64 mL 15% aq. MgSO4 was added 210 mg (1.4 mmol) KMnO4 in portions at 0 C. After stirring for 2 h at RT, the reaction mixture was diluted with water and extracted with chloroform. The organic phase was washed with saturated NaHCO3 and sat. NaCl, dried with Na2SO4 and evaporated. Yield 93 mg, 0.2 mmol, 74%.
Tetrahedron Asymmetry 2001, 2283 : page 2285
KMnO4 oxidation of 1-tetralin acetate:
To a cooled soln. of 1-acetoxytetralin (0.67 g, 3.54 mmol) in 15 ml acetone was added 2.08 g (8.43 mmol) MgSO4.7H2O and 5 ml water. To this mixture, 2.88 g (18.3 mmol) KMnO4 was added in small portions over 1 hour and stirred further for 4 h at RT. The solid was filtered off and the filtrate treated with satd. soln. of potassium metabisulfate. The resulting mixture was again filtered and extracted thrice with 25 ml DCM. The pooled extracts were washed with water, brine, and dried over Na2SO4. Solvent was removed and product chromatographed. Yield 0.46 g, 64%.
KMnO4 oxidation of 1-acetoxyindane:
Procedure was the same as above. Compound was prepared from acetoxyindane in 80% yield.
Finally, an oldie but goodie, for those who like the traditional methods. They use nitric acid on bentonite clay.
Synthetic communications 2002, 3565 : Natural bentonite clay / Dilute HNO3 (40%) -- A mild, efficient, and reuseable catalyst/reagent system for selective mono nitration and benzylic oxidations
General procedure for oxidation:
A dry 100 ml 2-necked RBF is fitted with a dean-stark trap and charged with 5.3 g (0.05 mol) ethylbenzene and 5 g bentonite clay. To this, 50 mL of hexane and 20 mL 40% HNO3 are added and refluxed for 5 h. At this time, water level in dean-stark trap remains constant and TLC shows completion. After filtering, solvent removal, and chromatography, there is collected acetophenone 5.3 g, 89%.
time(h) yield
ethyl benzene --> acetophenone 5 89%
diphenylmethane --> diphenylmethanol 5 81%
isobutylbenzene --> Isopropyl phenyl ketone 5 41% (??)
Unfortunately, the reaction is annoying and as the paper title indicates, it is probably that aromatic nitration is a competitive reaction. Nonetheless, for those who absolutely, positively can't get permanganate, it's nice to know that there may be alternatives.
http://journal.kcsnet.or.kr/publi/bul/bu01n2/141.pdf (http://journal.kcsnet.or.kr/publi/bul/bu01n2/141.pdf)
http://journal.kcsnet.or.kr/publi/bul/bu02n7/937.pdf (http://journal.kcsnet.or.kr/publi/bul/bu02n7/937.pdf)