novel synthesis of O-Acetyl-Mandelonitrile

[psyloxy]

Synthesis of 3,4,5-trimethoxybenzaldehyde cyanohydrin acetate and subsequent reduction thereof with Pd/H2 @ 1atm is described in

https://www.thevespiary.org/rhodium/Rhodium/chemistry/mescalyptus.html

Yield of acetylated mandelonitrile is only ~66% from the benzaldehyde. It involves the use of KCN.

In Ref[1] O-acetyl-mandelonitrile is prepared in 90% yield at ambient temp in 1 hour from benzaldehyde, 2-oxo-propionitrile and aq. K₂CO₃ soln. in acetonitrile.

No, I have not read the article. Yes, I want to know what it says,too.

Now, what is 2-oxo-propionitrile and how is it made ?

I hope you can guess it's structure from the following little ascii drawing:
             

H3C-C=O
     \
      CN

There must be a hundred ways to make it.

[2] Wacker oxidation of acrylonitrile @ 30°C
[3] from KCN and acetylbromide

Dehydration of 2-oxo-propionaldehyde oxime
[4] with P₂O₅ in CS₂
[5] with acetylchloride

Of these I think 2-oxo-propionaldehyde oxime holds the most promise for it can be prepared from acetone and

[6]ethylnitrite (74% - 45°C - 60min) [looks somewhat familiar,eh ?]
[7]methylnitrite / HCl
[8]AcOH / NaNO₂ at 0°C
[9]N₂CO₃ / Na₂[Fe(CN)₅NO] (sodium nitroprusside)

There are tons more ways out there but one thing sticks out especially: in

Patent US2980708

they describe the thermal rearrangement of easily made oxime-acetate
to nitrile by dry distillation. They use the corresponding epoxialdoximes_{(and produce the epoxinitriles which,in turn, can also be used to make the oxonitriles)} but it might as well work on the oxy-aldoxime, too.

comments eagerly awaited  

BTW: you may encounter the use of Ac₂O here and there if you're doing research into this topic, besides it's quite useful generally, may it be for the production of AcBr from Ac₂O and HBr, which may sound like the wrong way but have a look at

Patent US1430304

where Henry Dryefuss demonstrates how to make Ac₂O by simpy heating a mix of Na₂S₂O₇ and NaOAc. It has once been mentioned before by PolytheneSam but maybe wasn't recognized ??

[1] Okimoto, Mitsuhiro; Chiba, Toshiro; SYNTBF; Synthesis; EN; 10; 1996; 1188-1190.
[2] Smidt; Sieber; ANCEAD; Angew.Chem.; 71; 1959; 626.
[3] Mukherjee, Jogeshwar; Rogers, Janice I.; Khalifah, Raja G.; Everett, Grover W.; JACSAT; J.Amer.Chem.Soc.; EN; 109; 23; 1987; 7232-7233
[4] Scholl; MOCMB7; Monatsh.Chem.; 39; 1918; 238.
[5] Claisen; Manasse; CHBEAM; Chem.Ber.; 20; 1887; 2196
[6] Tajbakhsh, M.; Bakooie, H.; Ghassemzadeh, M.; Beheshtiha, Y. Sh.; Heravi, M. M.; IJSBDB; Indian J.Chem.Sect.B; EN; 40; 12; 2001; 1232 - 1233
[7] Slater; JCSOA9; J.Chem.Soc.; 117; 1920; 589.
[8] Kuester; HSZPAZ; Hoppe-Seyler's Z.Physiol.Chem.; 155; 1926; 180.
[9] Schmidt; ARPMAS; Arch.Pharm.(Weinheim Ger.); 250; 1912

--psyloxy--

[Rhodium]

A Convenient and Improved Method for the Preparation of Cyanohydrin Esters from Acyl Cyanides and Aldehydes
M. Okimoto & T. Chiba

Synthesis (10), 1188-1190 (1996)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/mandelonitrile-acetate.phcho-acetylcyanide.pdf)

[psyloxy]

So the autors indicate Ph-CO-CN can also be used. That made psyloxy look into preparation methods for this compound. Here's what he found.

[1]First let's prepare some acetoneoxime from, you guessed it, acetone and NH2OH.HCl. With the aid of Na₂CO₃ and hot aqu. EtOH 96% yield can be had in 24h.

In the 2nd step acetophenone is first oxidised to phenylglyoxaldehyde by DMSO/HBr then hydrated with H₂O to phenylglyoxylhydrate, refer to ex. XI in

Patent US3434064

[2]Said phenylglyoxalhydrate is then reacted with the aforementioned acetoneoxime + HCl for 2h in 50°C H₂O to give a 91% yield of oxo-phenyl-acetaldehyde oxime

[3] Finally oxo-phenyl-acetaldehyde oxime is dehydrated with Ac₂O to form oxo-phenylacetonitril

Now that reads 4 rxns at first sight. But look at them. Simple chems, simple (+mild) rxns, simple workup... pure chemical simplicity, no need to fool around with KCN, not even alkylnitrites! Well, from my theoretical point of view it all looks fine and dandy

[1]Langhals, Heinz; Range, Guenter; Wistuba, Eckehardt; Ruechardt, Christoph; CHBEAM; Chem.Ber.; GE; 114; 12; 1981; 3813-3830.
[2]Meester, Johan W. G. De; Plas, Henk C. van der; Middelhoven, Wouter J.; JHTCAD; J.Heterocycl.Chem.; EN; 24; 1987; 441-451.
[3]Hegarty, Anthony F.; Tuohey, Patrick J.; JCPKBH; J.Chem.Soc.Perkin Trans.2; EN; 1980; 1313-1317

--psyloxy--