Cyanoacetate, methyl

Physical Properties. The physical properties of cyanoacetic acid [372-09-8] NM7—CH2COOH (28) ate summarized in Table 4. The industrially most important esters ate methyl cyanoacetate [105-34-0] and ethyl cyanoacetate [105-56-6]. Both esters ate miscible with alcohol and ether and immiscible with water. 

Table 4. Physical Properties of Cyanoacetic Acid, Methyl Cyanoacetate, and Ethyl Cyanoacetate...

Property Cyanoacetic acid Methyl cyanoacetate Ethyl cyanoacetate... 

Manufacture. Cyanoacetic acid and cyanoacetates are iadustrially produced by the same route as the malonates starting from a sodium chloroacetate solution via a sodium cyanoacetate solution. Cyanoacetic acid is obtained by acidification of the sodium cyanoacetate solution followed by organic solvent extraction and evaporation. Cyanoacetates are obtained by acidification of the sodium cyanoacetate solution and subsequent esterification with the water formed being distilled off. Other processes reported ia the Hterature iavolve the oxidation of partially oxidized propionittile [107-12-0] (59). Higher esters of cyanoacetic acid are usually made through transesterification of methyl cyanoacetate ia the presence of alumiaiumisopropoxide [555-31-7] as a catalyst (60). 

Methyl cyanoacetate and ethyl cyanoacetate are produced by Lonza ia Switzerland and Hbls ia the United States, as well as Juzen and Tateyama ia Japan. The total production capacity is estimated to be ia the range of 10,000 metric tons per year. The market price for both esters ia bulk shipments was around 6/kg ia 1993. 

Methyl cyanoacetate [105-34-0] M 99.1, f -13 , b 205 , d 1.128, n 1.420. Purified by shaking with 10% Na2C03 soln, washing well with water, drying with anhydrous Na2S04, and distilling. 

Methyl chloroacetate, 7,17 Methyl cyanoacetate, 3, 56 Methylene Aminoacetonitrile, 4, 31,47... 

The molecular ion typically is not observed but can be deduced by adding 31 to the highest-mass peak observed (even in the case of methyl cyanoacetate). An intense ion in the mass spectra of methyl esters is m/z 74, formed in a McLafferty rearrangement. Also present is m/z 87, but it is of low intensity. Characteristic losses from the molecular ion are 31, 40 (small), 59, and 73 Daltons. 

Scheme 26, which recalls the classic reactions involved in the synthesis of 50 from small, common molecules, will help in following the methods used for labeling the imidazole ring of AIRs. Nitrosation with (l5N)NaN02 allowed the preparation of AIRs labeled on N-3. When methyl cyanoacetate was prepared with (i5N)KCN, AIRs labeled on the amino nitrogen were obtained. 

Methyl chloride-polystyrene, 56, 96 Methyl chloroformate, 59,195 Methyl (chlorosulfonyl)carbamate, 56,40 Methyl cyanoacetate, 56, 63 Methyl 2-(l-cyanocyclohexyl)diazene-carboxylate, 58, 102, 106... 

Cyclopropane carbonrtrile Methacrylonitrile Crotononitrile Anyl cyanide Methyl cyanoacetate Allyf isothiocyanate... 

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). 

Reaction of pyrido[ 1,2- pyrazin-4-one 304 with methyl cyanoacetate, cyanamide, and JI-oxo nitriles in AcOH at 70 °C gave imidazo[ l,2- ] pyridine 331, imidazo[l,2- ]-pyrimidine 332, and tetracyclic heterocycles 333, respectively <1996JHC639>. 

Methyl 2-butenoate 3-Methyl- 1-butyne 2-Methylbutyl acetate Methyl chloroacetate Methyl cyanoacetate Methyl cyclobutanecarboxylate Methylcyclohexane 6.75... 

Intermediates such as 224 resulting from the nudeophilic addition of C,H-acidic compounds to allenyl ketones such as 222 do not only yield simple addition products such as 225 by proton transfer (Scheme 7.34) [259]. If the C,H-acidic compound contains at least one carbonyl group, a ring dosure is also possible to give pyran derivatives such as 226. The reaction of a similar allenyl ketone with dimethyl mal-onate, methyl acetoacetate or methyl cyanoacetate leads to a-pyrones by an analogous route however, the yields are low (20-32%) [260], The formation of oxaphos-pholenes 229 from ketones 227 and trivalent phosphorus compounds 228 can similarly be explained by nucleophilic attack at the central carbon atom of the allene followed by a second attack of the oxygen atom of the ketone at the phosphorus atom [261, 262], Treatment of the allenic ester 230 with copper(I) chloride and tributyltin hydride in N-methylpyrrolidone (NMP) affords the cephalosporin derivative 232 [263], The authors postulated a Michael addition of copper(I) hydride to the electron-... 

The carbanion derived from dimethyl malonate reacts with the cyclic nitro compounds 422 of ring size 5, 6, 7, 8 and 12 to afford the corresponding esters 423. Acyclic allylic nitro compounds 424 (R = Me, CH2OAC or CC Et) are attacked by bulky nucleophiles, such as dimethyl malonate anion, mainly at the terminal primary carbon atom to give rearranged products 425, whereas smaller nucleophiles, e.g. the anion derived from methyl cyanoacetate, react at the tertiary carbon atom to yield 426409a 453 455. 

The reaction of the sulfonium salt 263 with methyl cyanoacetate in the presence of sodium methoxide was found to give exclusively the -isomer of (15,2/ )-l-cyano-2-phenylcyclopropanecarboxylie acid methyl ester 264 of 25.5% optical purity (296). 

Carrie and co-workers studied the cycloaddition of oxime esters derived from methyl cyanoacetate and malonate esters 82 (Scheme 8.20) with diazomethane and some monosubstituted derivatives. Thermally labile 1,2,3-triazolines 83 were obtained when tosyloxy- and benzoyloxyimines were used (141), while methyl acetoxyimino-cyanoacetate (82, X = CN, Y = C02Me, = Ac) gave products derived from both a 1,2,3- and a 1,2,4-triazoline, depending on the stmcture of the diazo compound (142). Not unexpectedly, diazomethane reacted with the corresponding imino-malononitrile (82, X = Y = CN) system at the nitrile function rather than at the C=N bond (143). 

The reactions of methyl 2-formyl-677 or 6-substituted furo[2,3-. ]pyrrole-5-carboxylates 31d-f or 154 <1997MOL69, 1999CCC1135> with malononitrile, methyl cyanoacetate, and 2-furylacetonitrile, respectively, afforded the corresponding methyl 2-(2,2-dicyanovinyl)-677- or 6-substituted furo[2,3-. ]pyrrole-5-carboxylates 294a-d, methyl 2-[2-cyano-2-(methoxycarbonyl)vinyl]-677- or 6-substituted furo[2,3-. ]pyrrole 5-carboxylates 295a-d, and methyl... 

Synthesis of tetrahydropyrido[2,3-,y pyrimidin-7-ones 537 in a microwave-assisted one-pot cyclocondensation of a,/3-unsaturated esters with active methylene compounds (malononitrile or methyl cyanoacetate) and amidine salts (guanidine or benzamidine) in NaOMe/MeOH for 10min has been reported <2003TL5385>. 

Methyl cyanoacetate can also be made by this method, if methyl alcohol be used instead of ethyl alcohol. 

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