Butyl cyanoacetate

The preparation of malonic acid monoesters has been demonstrated using the microbial nitrilase activity of Corynebacterium nitrilophilus ATCC 21 419, Gordona terrae MA-1, or Rhodococcus rhodochrous ATCC 33 025 to hydrolyze methyl cyanoacetate, ethyl cyanoace-tate, M-propyl cyanoacetate, isopropyl cyanoacetate, M-butyl cyanoacetate, tertbutyl cyanoacetate, 2-ethylhexyl cyanoacetate, allyl cyanoacetate, and benzyl cyanoacetate [96]. By maintaining the concentration of nitrile in a reaction mixture at <5 wt%, significant inactivation of the nitrilase activity was avoided for example, a total of 25 g of M-propyl cyanoacetate was added in sequential 5g portions to a lOOmL suspension of Rhodococcus rhodochrous ATCC 33 025 cells (OD630 = 5.6) in 50 mM phosphate buffer (pH 7.0) over 30h at 25 °C to produce mono-M-propyl malonate in 100% yield (Figure 8.17). 

The present preparation employs a method of considerable scope which gives much better yields and is considerably less laborious than other methods for the preparation of tert-butyl cyanoacetate. The compound is of specific interest since, for example, it may be used in any reaction where ethyl cyanoacetate is used (condensation reactions, etc.), but it has the added advantage that the carbo-feri-butoxy group, which may serve in conjunction with the a-cyano group to activate the a-hydrogens (for cyanoethylations, etc.), may be later removed simply by pyrolysis of the compound. 

ZerZ-Butyl cyanoacetate [1116-98-9] M 141.2, b 40-42 /0.1mm, 54-56 /0.3mm, 90 /10mm, 107-108 /23mm, d 0.989, 0 1.4198. The IR spectrum of a film should have bands at 1742 (ester CO) and 2273 (C=N) but not OH band (ca 3500 broad) cm . If it does not have the last named band then fractionally dist, otherwise dissolve in Et2O, wash with satd aq NaHCO3, dry over K2CO3, evap Et2O, and dist residue under a vacuum (see tert-butyl ethyl malonate for precautions to avoid decomposition during distn). [JCS 423 7955 HCA 42 1214 7959]. 

Chloro-l,10-phenanthroline (69) reacts with the sodium salt of tert-butyl cyanoacetate to give the intermediate 105, which with cold hydrochloric acid affords 2-cyanomethyl-1,10-phenanthroline (106).345 2-Chloro-1,10-phenanthroline also participates in the Ullmann reaction to afford 2,2 -bi-(l,10-phenanthroline) (I07).346 5,5 -Bi-(l,10-phenanthroline) was also prepared, but by a different route starting from 8,8 -diamino-6,6 -biquinoline. 

If acid was added there was a marked decrease in absorbance around 250 inn. The difference spectrum, a plot of fall in absorbance versus wavelength, was found to be identical to the spectrum of sodium butyl cyanoacetate (Na CH(CN)COOBut). If the initiator was triphenylphosphine the absorption remaining after addition of acid was identical to triphenyl-methylphosphonium bromide. Repetitive isolation and purification of the polymer did not reduce the intensity of this absorption. Assuming that the absorption coefficients of the model compounds and chain ions were identical it could be shown that molarities of polymer, cation, and anion were equal to the initiating phosphine concentration. 

The oxidation of acetate by peroxodisulphate is much slower than that of formate. Glasstone and Hickling showed that the products, which include carbon dioxide, methane, ethane, and ethylene, are similar to those produced by the anodic oxidation of acetate ions (Kolbe electrolysis), and they inferred that the same organic radicals are formed as intermediates. Similar results are reported by Eberson et al. for the oxidations of ethyl terf.-butyl-malonate, tert.-butyl-cyanoacetate, and ferl.-butyl-malonamate ions. The oxidations of these ions and of acetate by peroxodisulphate are first order with respect to peroxodisulphate and zero order with respect to the substrate. Mechanisms involving hydroxyl radicals are excluded because the replacement of peroxodisulphate by Fenton s reagent leads to different products, so Eberson et al. infer that the initial attack on the substrate is by sulphate radical-ions. Sengar and Pandey report that the rate of the silver ion-catalysed oxidation of acetate is independent of the peroxodisulphate concentration. 

Kato and his coworkers constructed the aryl-Cs unit by DEPC [(Et0)2P(0)CN)] mediated C-acylation of /-butyl cyanoacetate with phenylpropanoic acid leading, as the key intermediate, to the acetalized beta-ketoaldehyde 148 (114). Addition of 2-phenylethyI magnesium bromide followed by deprotection of die carbonyl group completed the synthesis of the racemic P-ketol 6. Acid catalyzed elimination of water from 6 finally provided the enone 28. 

Common synthetic methods for the preparation of cyclic 8-enamino esters are the condensation between a lactim ether and benzyl cyanoacetate followed by hydrogenolytic decarboxylation, or the imino ester carbon-carbon condensation with tert-butyl cyanoacetate followed by a trifluoroacetic acid treatment. The use of a thiolactam condensed with ethyl bromoacetate gives, after sulfur extrusion by triphenylphosphine, cyclic 8-enamino esters. Compared with these methods, the Meldrum s acid condensation followed by the monodecarboxylating transesterification described here is more convenient and practical. An extension of this procedure permits preparation of smaller... 

Compound (248), a relative of [14] annulene containing a hydrazine bridge, has been synthesized by a Knoevenagel condensation of the [l,r-bipyrrole]-2,2 -dicarbaldehyde (247) and r-butyl cyanoacetate, followed by reduction of the exo double bond with diisobutylhaluminum hydride, acid-catalyzed cycliza-tion, and decarboxylation.283... 

Michael reaction of a-substituted t-butyl cyanoacetates to t-butyl prop3moate establishes a quaternary carbon center in the adducts. Excellent asymmetric induction is achieved by much more bulky ammonium salt. ... 

A double Michael addition has been observed in the intermolecular reaction of the a, p-unsaturatedacylanthraquinone, 1 -hydroxy-2-(1 -oxopent-2-enyl)anthra-quinone illustrated with tert-butyl cyanoacetate followed by an intramolecular cyclisation of the product. The whole sequence was conducted at ambient temperature during 6 hours in dimethylformamide to give a substituted benzohydroxyanthraquinone in 75% yield (ref.84). 

Methyl-thIoethyl-(1 -methyl)-n-butyl-cyanoacetic acid ethyl ester... 

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