Formylacetal

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). 

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... 

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... 

Chemical/Physical. Hydrolysis in distilled water at 25 °C produced 3-chloro-2-propen-l-ol and HCl. The reported half-life for this reaction is only 2 d (Kollig, 1993 Milano et al., 1988). trans-1,3-Dichloropropylene was reported to hydrolyze to 3-chloro-2-propen-l-ol and can be biologically oxidized to 3-chloropropenoic acid which is oxidized to formylacetic acid. Decarboxylation of this compound yields carbon dioxide (Connors et al., 1990). Kim et al. (2003) reported that the disappearance of tra 35-l,3-dichloropropylene in water followed a first-order decay model. At 25 and 35 °C, the first-order rate constants were 0.083 and 0.321/d, respectively. The corresponding hydrolysis half-lives were 8.3 and 2.2 d, respectively. 

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. 

The formation of 2-oxopyran-5 -carboxylic acid (coumalic acid) from 2-hydroxybutanedioic acid (malic acid) is described in detail (63OSC(4)20l) and involves the decarbonylation and dehydration of the hydroxy acid. The formylacetic acid so formed then undergoes selfcondensation. This synthesis is an example of the Pechmann reaction usually associated with the synthesis of coumarins (benzopyran-2-ones). It will be observed that this route leads to pyran-2-ones which carry identical substituents at the 4- and 6-positions. 

Coumarins unsubstituted in the heterocyclic ring may be obtained by using 2-hydroxy-butanedioic acid (malic acid). Concentrated sulfuric acid decomposes this acid with loss of carbon monoxide and water to formylacetic acid, which is of course a 1,3-dicarbonyl compound and reacts as such with the phenol (Scheme 111). It is sometimes advantageous to use a mixture of sulfuric and acetic acids, which reduces the extent of formation of tarry material. 

In the synthesis (Expt 8.34), formylacetic acid is formed in situ by the action of a concentrated sulphuric acid-fuming sulphuric acid mixture on malic acid (H02OCH0H CH2 C02H). This a-hydroxydicarboxylic acid undergoes decarbonylation and dehydration under these conditions before the acid-catalysed self-condensation of formylacetic acid. The cyclisation step is generally applicable to / -keto esters. 

The a-diazo-/ -hydroxy ester 1 rearranges under the same conditions to the formylacetic ester 2. 

The precipitated yellow solid during the reaction is 6-phenyl-3-nitro-2-pyridone 28g whose C2 - C3 - C4 unit is derived from the C4 - C5 - C6 unit of pyrimidinone 3. Another TCRT proceeds at the 4- and the 6-positions of pyrimidinone 3, which behaves as the synthetic equivalent of a-nitro-formylacetic acid 29. 

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

The hydrazone of a 5-formylpyrimidine (114) when treated with sodium hydride and then heated to 150°C also results in formation of a pyrrolopyrimidine (115) (Equation (36)) <89H(29)1993>. In a related reaction, treatment of 2,4-diamino-6(l//)-oxopyrimidine (116) with methyl chloro-formylacetate gives both the pyrrolopyrimidine (117), and the furopyrimidine (118) (Equation (37)) <89JCS(Pl)2375>. The latter can be converted into pyrrolopyrimidine products. Pyrrolopyrimidines with 5-amino substituents can be prepared from 5-cyanopyrimidines utilizing similar chemistry <88LA633>. 

Application of the principles of disconnection in heterocyclic rings to coumalic acid (92) reveals two molecules of formylacetic acid. 

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

Aminopyruvic acid (267) and 2-amino-2-formylacetic acid (268) gave 2, 6-pyrazinedicarboxylic acid (269) (no details).1586... 

The particular reaction described in Scheme 2 using dimethyl diazomalonate produces oxazoles 5 that bear a methoxy group at C-5. If desired, this substituent may be removed in some cases by reductive cleavage using LiB(Et)3H to give the 5-unsubstituted oxazoles 6.3.15 Alternatively, the 5-unsubstituted derivatives 6 may be obtained directly through the use of diazo formylacetate (2) in place of dimethyl diazomalonate (1).3 15 Some additional, representative examples of the use of 1 and 2 are shown below in the Table. 

ADDITIONAL EXAMPLES OF OXAZOLE FORMATION USING DIMETHYL DIAZOMALONATE 1 AND DIAZO FORMYLACETATE 2a... 

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