Formamides compounds

Diterpene isothiocyanates fall into three distinct structural categories regarding their carbon skeletons the acyclic tetraenes (220 and 221), the biflorane framework (including the kalihinol family) (222-238), and the amphilectane framework (including the cyclo- and isocycloamphilectanes) (239-241). Like the sesquiterpene isothiocyanates, most of these compounds were isolated along with the corresponding isocyanate and formamide compounds. 

The desired pyridylamine was obtained in 69 % overall yield by monomethylation of 2-(aminomethyl)pyridine following a literature procedure (Scheme 4.14). First amine 4.48 was converted into formamide 4.49, through reaction with the in situ prepared mixed anhydride of acetic acid and formic acid. Reduction of 4.49 with borane dimethyl sulfide complex produced diamine 4.50. This compound could be used successfully in the Mannich reaction with 4.39, affording crude 4.51 in 92 % yield (Scheme 4.15). Analogous to 4.44, 4.51 also coordinates to copper(II) in water, as indicated by a shift of the UV-absorption maximum from 296 nm to 308 nm. 

Ai,A/-bis(hydroxymethyl) formamide [6921-98-8] (21), which in solution is in equiUbrium with the monomethylol derivative [13052-19-2] and formaldehyde. With ben2aldehyde in the presence of pyridine, formamide condenses to yield ben2yhdene bisformamide [14328-12-2]. Similar reactions occur with ketones, which, however, requite more drastic reaction conditions. Formamide is a valuable reagent in the synthesis of heterocycHc compounds. Synthetic routes to various types of compounds like imida2oles, oxa2oles, pyrimidines, tria2ines, xanthines, and even complex purine alkaloids, eg, theophylline [58-55-9] theobromine [83-67-0], and caffeine [58-08-2], have been devised (22). 

In addition to the processes mentioned above, there are also ongoing efforts to synthesize formamide direcdy from carbon dioxide [124-38-9J, hydrogen [1333-74-0] and ammonia [7664-41-7] (29—32). Catalysts that have been proposed are Group VIII transition-metal coordination compounds. Under moderate reaction conditions, ie, 100—180°C, 1—10 MPa (10—100 bar), turnovers of up to 1000 mole formamide per mole catalyst have been achieved. However, since expensive noble metal catalysts are needed, further work is required prior to the technical realization of an industrial process for formamide synthesis based on carbon dioxide. 

Methanol can be converted to a dye after oxidation to formaldehyde and subsequent reaction with chromatropic acid [148-25-4]. The dye formed can be deterruined photometrically. However, gc methods are more convenient. Ammonium formate [540-69-2] is converted thermally to formic acid and ammonia. The latter is trapped by formaldehyde, which makes it possible to titrate the residual acid by conventional methods. The water content can be determined by standard Kad Eischer titration. In order to determine iron, it has to be reduced to the iron(II) form and converted to its bipyridyl complex. This compound is red and can be determined photometrically. Contamination with iron and impurities with polymeric hydrocyanic acid are mainly responsible for the color number of the merchandized formamide (<20 APHA). Hydrocyanic acid is detected by converting it to a blue dye that is analyzed and deterruined photometrically. 

Aromatic and heterocycHc compounds are formylated by reaction with dialkyl- or alkylarylformamides in the presence of phosphoms oxychloride or phosgene (Vilsmeier aldehyde synthesis) (125). The Vilsmeier reaction is a Friedel-Crafts type formylation (126), since the intermediate cation formed by the interaction of phosphoms oxychloride with formamide is a typical electrophilic reagent. Ionic addition compounds of formamide with phosgene or phosphoms oxychloride are also known (127). 

In the examples, a nitro group is substituted for a hydrogen atom, and water is a by-product. Nitro groups may, however, be substituted for other atoms or groups of atoms. In Victor Meyer reactions which use silver nitrite, the nitro group replaces a hahde atom, eg, I or Br. In a modification of this method, sodium nitrite dissolved in dimethyl formamide or other suitable solvent is used instead of silver nitrite (1). Nitro compounds can also be produced by addition reactions, eg, the reaction of nitric acid or nitrogen dioxide with unsaturated compounds such as olefins or acetylenes. 

Silicate Grouts. Sodium silicate [1344-09-8] h.3.s been most commonly used in the United States. Its properties include specific gravity, 1.40 viscosity, 206 mPa-s(=cP) at 20°C Si02 Na20 = 3.22. Reaction of sodium silicate solutions with acids, polyvalent cations, such organic compounds as formamide, or their mixtures, can lead to gel formation at rates, which depend on the quantity of acid or other reagent(s) used. 

Amino-pyridazines and -pyridazinones react with monomethyl- or iV,A-dimethyl-formamide and other aliphatic amides in the presence of phosphorus trichloride, thionyl chloride, phosgene or benzenesuUonyl chloride to give mono- or di-alkylaminomethyl-eneamino derivatives. The same compounds can be prepared conveniently with A,iV-dimethylformamide dimethyl acetal in high yield (Scheme 50). 

Once again, frequency shifts provide a good way of examining the solvent effect. The highly polar solvent produces about the same shift for each compound with the exception of fortnamide, where it is quite a bit greater, the result of combining the polar solvent with formamide s rather large dipole moment. ... 

Examine the geometry of formamide. Is the CN bond shorter than expected for a normal single bond (in methylamine), and closer to that expected for a full double bond (in methyleneimine) Is the CO bond longer than that expected in a carbonyl compound (in formaldehyde), perhaps closer to that appropriate for a single bond (in methanol) Also, compare the electrostatic potential map for formamide with those of formaldehyde and methylamine. Is the CO bond in formamide more or less polar than that in formaldehyde Is the CN bond in formamide more or less polar than that in methylamine Draw whatever Lewis structures are needed to properly describe the geometry and charge distribution of formamide. 

Good yields of pyrido[2,3-d]pyrimidiries (37) were also oblaiiied by the action of formamide on o-amino nitriles (36). Reduction of 2-amino-4,6-dimethylnicotinitrilc yields the 3-aminomcthyl compound (38). Acylation to the 3-aoylaminomethyl derivative (39), followed by cyolization, by means of heat or phosphoryl chloride, yielded the dihydropyrido[2,3-d]pyrimidines (40). ... 

The utility of 2,2 -biindolyl derivatives as indolocarbazole precursors has also been exploited extensively by Somei and co-workers, who reported the first syntheses of the naturally occurring indolo[2,3-a]carbazoles 16 and 17 (Scheme 9). A chloroacetylation of 2,2 -biindolyl (46) followed by treatment of the resulting product 58 with sodium cyanide in formamide-methanol provided 59. Transformation of 59 into the acetoxy derivative 60, followed by hydrolysis to 61, finally led to the target compounds after subsequent sequential melhylations [97H(45)1647]. 

In the authors opinion (81UK1252), the evidence for such a scheme is the isolation of formamide transamination products, dialkylformamides (in case of l-dialkylaminoalk-l-en-3-ynes). Examples of formamide transamination, e.g., by /3-amino-substituted carbonyl compounds, are known [58CB2832 60CB1402 60HC( 14)272],... 

A derivative of an isomeric azapurine ring system interestingly exhibits bronchodilator activity, possibly indicating interaction with a target for theophylline. The starting pyridazine 97 is available from dichloro compound 96 by sequential replacement of the halogens. Treatment of 97 with formic acid supplies the missing carbon and cyclizes the intermediate formamide with consequent formation of zindotrine (98) [16]. 

Compound 1567 CB and chloracetone are caused to react as in (B), the mineral salts subsequently filtered, 12 ml of concentrated hydrochloric acid are added to the solution in dimethyl formamide without dilution with water, and the mixture heated for 40 minutes on a water bath. The product crystallizes in the warm mixture, the mixture is cooled to room temperature, filtered, the residue washed with water and crystallized from acetic acid. MPc = 222°C. Yield 60% based on compound 1567 CB. 

Whilst some organic compounds can be investigated in aqueous solution, it is frequently necessary to add an organic solvent to improve the solubility suitable water-miscible solvents include ethanol, methanol, ethane-1,2-diol, dioxan, acetonitrile and acetic (ethanoic) acid. In some cases a purely organic solvent must be used and anhydrous materials such as acetic acid, formamide and diethylamine have been employed suitable supporting electrolytes in these solvents include lithium perchlorate and tetra-alkylammonium salts R4NX (R = ethyl or butyl X = iodide or perchlorate). 

Arenediazoisocyanides (Ar —N2NC) were synthesized by Ignasiak et al. (1975) by reaction of arenediazonium ions with formamide and dehydration of the resulting l-aryl-3-formyltriazene with thionyl chloride (Scheme 6-19). These compounds are interesting in the context of the (Z)/( )-isomerism of diazocyanides (see Sec. 6.6). 

Non-aqueous microemulsions have been prepared by replacing water with formamide, a highly structured polar solvent [71]. Formamide enhances the solubility of organic compounds and is also used as a reactant. 

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