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Nucleophilic aromatic substitution with ethyl cyanoacetate;  2-carboxyethyl- 2'-nitro-4'-chloro benzyl cyanide

SyntheticPage 557
DOI: 10.1039/SP557
Submitted May 03, 2012, published May 07, 2012
Ramesha Ramakrishna (ramesha63@hotmail.com)
A contribution from ramesha


			Reaction Scheme: <img src="/images/empty.gif" alt="" />Nucleophilic aromatic substitution with <span id="csm1341246363243" class="csm-chemical-name" title="ethyl cyanoacetate">ethyl cyanoacetate</span><img src="/images/empty.gif" alt="" />

Chemicals Used

2,5-Dichloronitrobenzene -commercial ,purity by GC min 98%
Ethylcyanoacetate - from S. D. Fine Chem, LR grade
Potassium carbonate powder
Tetrabutylammonium bromide - S D Fine Chem, LR grade
Dimethyl formamide
Ethyl acetate

Procedure

Dimethylformamide (30 mL), 2,5-dichlorobenzene (9.6 g, 0.05 mole), ethyl cyanoacetate (6.2 g, 0.055 mol) are charged to a 100 mL round bottomed flask. To this tetrabutylammonium bromide(0.5 g, 5% by weight to dichloronitrobenzene) was added, followed by powder potassium carbonate (7.6 g, 0.055 mol) all at once and stirred at room temperature (25-35 oC) for 16 hours. Reaction mixture turns dark red in 10-15 min. TLC shows complete disappearance of 2,5-dichloronitrobenzene after about 15 h. The reaction mixture diluted with ethylacetate (200 mL) and added into water (200 mL). The reaction mixture was acidified to about pH 6 with dilute HCl. At this time the dark red color turns to light yellow. Water layer was separated and discarded. Ethyl acetate was given water wash and dried over sodium sulphate( 25-30 g). The ethyl acetate layer thus obtained was concentrated to get the condensed product as a viscous oil - 12.8 g. This is purified by column chromatography using petroleum ether: ethyl acetate (97:3) on silica gel to get 10.7 g (79%)

Author's Comments

1. It is important to use powder potassium carbonate for the complete reaction. Granular potassium carbonate gives low yield/incomplete conversion.

2. The reaction medium turns red because of the formation of potassium salt of the product.

3. It is essential to acidify the reaction mixture during workup. This has two advantages. 1-high yield, 2- better colour for the product.

4. The active Methylene here is very reactive and can be further functionalized easily.

Data

1H NMR (300 MHz): 8.22 (S, 1H), 7.73 (s, 2H), 5.63 (s,1H), 4.30 (q, 4H), 1.32 (t, 6H)

13C NMR (75 MHz): 163.12, 147.66, 136.70, 134.41, 132.48, 126.26,123.66, 114.06, 64.09, 40.80, 24.70, 13.83.


Lead Reference

No excact reference

Other References

V.M.Vlasov, " Nucleophilic substitution of the nitro group, fluorine, chloride in aromatic compounds". Russian Chemical Review, 1990, 59, 514-530. http://dx.doi.org/10.1070/RC1990v059n06ABEH003540

Supplementary Information

1H NMR DCNB.bmp
13C NMR DCNB.bmp

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Keywords: aromatics/arenes, dichloronitrobenzene, esters, Ethylcyanoacetate, nucleophilic, substitution

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  • Guest PatrickJul 2 2012 4:27PMreference error

    I can't seem to track down the reference. Is it correct?

    • Guest Dr. Ramesha A. RJul 3 2012 4:22AMreference

      Dear Dr.Patrick The reference to this article was general article on aromatic nucleophillic substitution. This is not exactly related to this methodology. This method was developed by us in out R&D. The following reference is closely related: Grob, G.A; Weissbach, O. Helvetica Chemica Acta, 1961, Vol 207, p1748-1753

      • Registered user Peter ScottJul 3 2012 9:31AMreference

        Hi Ramesha, Patrick asked if the reference was correct. I added a DOI to what seems to correspond. The Authors seem to be incorrect however. Perhaps Ramesha can clear this up by confirming the doi link and letting me have a corrected reference if appropriate? PSc

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