Is there anyone who tried to prepare 4-acetyl-3-phenyl sydnone using 1,3-Dibromo-5,5-dimethylhydantoin (DBH) as a catalyst as described by Azarifar et al, 2007. I have tried it on various 3-phenyl sydnone analogues without any results. I always end up with the starting material, even TLC didn't indicate the formation of new product. Any suggestion or advice from experts!
This is the method as described in the paper: "To a stirred solution of 3-arylsydnone 1a-j (1 mmol) in acetic anhydride (2 mmol) was added DBH (0.29 g, 1 mmol), and the mixture was refluxed at 100 °C for 7 h. After complete conversion of the substrates as indicated by TLC using ethylacetate/hexane mixture (1:1), the resulting reaction mixture was poured into ice water to destroy the excess acetic anhydride and neutralized with sodium carbonate. The resulting mixture was filtered, the filtrate was extracted with CH 2 Cl 2 (2x25 mL), and then dried with anhydrous MgSO 4 . After filtration, the solvent was evaporated under reduced pressure to leave a solid brown residue, which was recrystallized from warm ethanol (95%) to yield pure crystals of the products 2a-j in 80-92% yield (Table 1)."
Greetings
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3884322/
http://rasayanjournal.co.in/vol-2/issue-1/22.pdf
http://www.hrpub.org/download/201310/ujc.2013.010306.pdf
1) silica supported DBH will be useful.
2) Try alternate bromination followed by acetylation
Alternatively try direct acylation with following condition.
Reagents
1. RCO2H, P2O5
2. Ac2O, BF3·Et2O
3. Ac2O, HClO4
4. Ac2O, Montmorillonite K-10
5. (RCO)2O, Bi(OTf)3
6. (RCO)2O, Bi(OTf)3/ LiClO4
Try first the bromination with DBH (Asraf, Synthesis 2006, 1123) in DMF..see how it goes!
We recently published a study where DBH was used to brominate N-heterocycles. We used catalytic amounts of Brønsted acids to activate the reagent. Have a look on the conditions, maybe they can be applied to your system.
Link: http://onlinelibrary.wiley.com/doi/10.1002/adsc.201200723/abstract
@Kachapur Arunkumar:
Actually, the conventional acylation using P2O5 or BF3 give very low yield (30-40%) and the yield will be even lower when the aryl moiety contains NO2 group (less than 15%). The other methods using alkyl anhydride and bismuth triflate were very successful for this type of acylation giving a yield up to 70-85% when Ar contains Me, OMe, Cl, Br, etc., while when I use it for the acylation of 3-(4/3-nitrophenyl)sydnone was not successful even after 4 days of reflux.
On the other hand, the paper using DBH reported a successful acylation of 3-(4/2-nitrophenyl)sydnone with a yield up to 80%, hence when I try it, it didn't work with either sydnone.
@Alexander H. Sandtorv:
Thanks for the link, it seems feasible and I will try it.
If you notice in the method mentioned above, they dissolve 1 mmol (# 0.2 g) of the sydnone in 2 mmol (188 ul) acetic anhydride, which is impractical as I tried it in the lab. I think they didn't mention the solvent that they used as a medium for the reaction. I have tried i-PrOH, Benzene, CH3CN, Et3N but didn't work.
If you notice in the method mentioned above, they dissolve 1 mmol (# 0.2 g) of the sydnone in 2 mmol (198 ul) acetic anhydride, which is impractical as I tried it in the lab. I think they didn't mention the solvent that they used as medium for the reaction. I have tried i-PrOH, Benzene, CH3CN, Et3N but didn't work....
but what if they use acetic anhydride as solvent..did you try with large excess?
@Marcel Mirel Popa
Yeah, sure I tried it as the first choice and it failed also .
I also think a large excess of acetic anhydride as solvent makes sense. In many acetylation reactions this is employed to drive the reaction to completion.
Ya i agree with Alexander , generally DBH is activated by LA.
The following condition can be tried
1) DBH/TMSOTf combination in polar aprotic solvents such as CH3CN and DMF.
2) DBDMH in concentrated H2SO4 or CF3SO3H
(without solvent the above combination used generally for deactivated substrates having NO2 group ) , then followed by acetylation .
Abdualkader,
You can use this reported method instead using Bismuth Triflate Catalyzed Friedel-Crafts Acylation of 3-Phenyl- analogue under MW condition
---Balaguer, Amanda M.; Rumple, Amber C.; Turnbull, Kenneth, Organic Preparations and Procedures International (2014), 46(4), 363-369.
---Balaguer, Amanda et al, Synthetic Communications, (2013) 43(12), 1626-1632.
OR
May may use N-Bromosuccinimide (NBS) as promoter for acylation of sydnones in the presence of acetic anhydride under neutral conditions. See
---Ghasemnejad-Bosra, Hassan et al, Heterocycles, (2008) 75(2), 391-395.
Good luck
Abdualkader,
may use acetyl chloride instead of anhydride acetic in reported method.
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