Ethyl formylacetate

In 1959 a new non-protein L-a-amino acid was isolated from the seeds of Acacia willardiana and later from other species of Acacia-, it proved to be l-/3-amino-/3-carboxyethyluracil (977) (59ZPC(316)164). The structure was confirmed by at least four syntheses in the next few years. The most important involves a Shaw synthesis (Section 2.13.3.1.2e) of the acetal (975) and hydrolysis to the aldyhyde (976) followed by a Strecker reaction (potassium cyanide, ammonia and ammonium chloride) to give DL-willardiine (977) after resolution, the L-isomer was identical with natural material (62JCS583). Although not unambiguous, a Principal Synthesis from the ureido acid (978) and ethyl formylacetate is the most direct route (64ZOB407). 

C3H9O2 109-94-4) see Danazol Drostanolone Fluorouracil Formeboloue, Metapramine Oxymetholone Perhexiline Stanozolol Tetroxoprim Trilostane Trimethoprim ethyl formylacetate... 

The primarily formed azetidinone derivative 427 isomerized to the octahydropyrimido[l,2-fl]azepin-4-ones 428 above 130°C (70CB1797) Compound 429 was also obtained in the reaction of 2-amino-3//-4,5,6,7-tetrahydroazepine hydrochloride (414-HCl R = H) and the sodium salt of ethyl formylacetate (83JOC2914). 

Derivation Hydrolysis of nucleic acids, precipitation from urea and ethyl formylacetate. Radioactive forms available. 

Thiouracil. 2,3-Dihydro-2-ihioxo-4(IH)-pyri-midinone 2-mercapto-4-hydroxypyrimidine 4-hydroxy -2( I ft) -pyrimidinethione 2 -mercapto -4( 1H) -py rimidinone 6 -hydroxy -2 -mercaptopyrimidine 2-mercapto-4. pyrimi -done Deracil. C4H4N,OS mol wt 128.15. C 37.49%, H 3.15%, O 12.48%, N 21.86%, S 25 02%. Occurs in seeds of Brassica, Cruciferae Purves, Brit. J. Exp. Pathol 22, 241 (1941). Prepd by condensing ethyl formylacetate with thiourea Wheeler. Liddle, 3m. Chem. J. 40, 550(1908). Antithyroid activity results from its interference with the iodina-tion of thyroxine precursors see Maloof, Soodak, Pharmacol. Rev. 15, 72-79 (1963). Inhibition of nucleic acid metabolism Cardeilhac, Proc, Soc. Exp. Biot Med. 125, 692 (1967). Toxicology K. K. Carroll, R. L, Noble, J. Pharmacol. Exp. Ther. 97, 478 (1949). 

Ethyl formylacetate and diethyl 3-oxoglutarate have afforded modest yields of... 

Only 2-alkylthiopyrimidines are made by the Principal Synthesis, using 5-alkylthiourea as one component. For example, ethoxymethylenemalononitrile (877) and 5-benzylthiourea in aqueous acetone at 20 °C give 4-amino-2-benzylthiopyrimidine-5-carbonitrile (878) (61JOC79) and ethyl 2-allyl-2-formylacetate and 5-methylthiourea in aqueous ethanolic alkali give 5-allyl-2-methylthiopyrimidin-4(3H)-one (6UOC4425). 

An intermediate a-bromo-a-formylacetate hemiacetal has been prepared by reaction of ethyl (3-ethoxyacrylate with A-bromosuccinimide (NBS). Cyclizat-ion of the in situ formed hemiacetal with thioureas affords 2-amino-1,3-thiazole-5-carboxylates (Scheme 58).141... 

Carbon tetrachloride. Chloroform, 2-Chlorophenol, Cyclohexanol, Cyclopentene, 1,1-Dichloroethylene, irans-l, 2-Dichloroethylene, IV.yV-Dimethylaniline, lV,lV-Dimethylformamide, 2,4-Dimethylphenol, 2,4-Dinitrotoluene, 1,4-Dioxane, 1,2-Diphenylhydrazine, Ethyl formate. Formaldehyde, Glycine, Methanol, Methylene chloride. Methyl formate, 2-Methvlphenol. Monuron, 4-Nitrophenol, Oxalic acid, Parathion, Pentachlorophenol, Phenol, l idine. Styrene, Trichloroethylene, Vinyl chloride Formylacetic acid, see cis-l,3-Dichloropropylene, irans-1,3-Dichloropropylene IV-Formylcarbamate of 1-naphthol, see Carbaryl Formyl chloride, see Chloroethane, Chloroform, sym-Dichloromethyl ether, ds-1,3-Dichloropropylene, irans-ES-Dichloropropylene, Methyl chloride. Methylene chloride. Trichloroethylene, Vinyl chloride lV-Formyl-4-chloro-o-toluidine, see Chlornhenamidine. 

Ethyl 2-chloro-2-formylacetate Barium hydroxide octahydrate Lithium aluminum hydride 4-Nitrophenyl chloroformate Phosphorus pentasulfide Methylamine... 

Hydroxyiminopropionaldehyde dimethyl acetal (264) and ethyl 2-formamido-2-formylacetate (265) gave ethyl 5-methyl-2-pyrazinecarboxylate 4-oxide (266) (HCl/AcMe, reflux %).1167... 

A new facile synthesis of 2-aminothiazole-5-carboxylales has been developed which does not involve the preparation and isolation of a-formyl-a-haloacetates. The reaction of ethyl (3-ethoxyacrylate 45 with N-bromosuccinimide afforded the a-bromo-a-formylacetate hemiacetal 46. In situ cyclisation of this intermediate with thioureas gives 2-aminothiazole-5-carboxylates 47 in good to excellent yields <01TL2101>. 

Some applications of the described reactions include the preparation of chloroquine, an important anti-malarial, which is made by reacting 4,7-dichloroquinoline with 4-diethylamino-l-methylbutylamine at 180 °C. 7-Chloro-4-hydroxyquinoline, a precursor of 4,7-dichloroquinoline, was routinely prepared by heating 3-chloroaniline with the ethyl ester of formylacetic acid, through the Conrad-Limpach quinoline synthesis. ... 

Condensation of [ CJthiourea with ethyl 2-formylacetates or their diethyl acetals provides 6-hydroxy-2-mercapto[2- C]pyrimidines 53 (Figure 9.14). Subsequent acid-... 

---