Formamide-formic acid complex

This overview analyzes the electron redistribution that takes place in two interacting monomers upon H-bond formation. The systems selected (shown in Fig. 1) focus on the two most important classical H-bonds, O-H- O and N H- O, and cover both donor and acceptor roles of every monomer. They are the following (a) water dimer (WD), (b) methanol water complex (MW), (c) water methanol complex (WM), (d) formic acid dimer (FAD), (e) forma-mide dimer (FD), and (f) formamide-formic acid complex (FFAC). Systems (a)-(c) are bound by one single O-H- 0 bond whereas cyclic dimers (d)-(l) are linked by two H-bonds. In FAD and FD homodimers, both monomers behave simultaneously as donor and acceptor while in the FFAC heterodimer, for-mamide and formic acid play competing roles. 

These reactions are typified by Bredereck s formamide synthesis . This has been applied to the synthesis of 4,5-dimethylimidazole (as its formic acid complex) from acetoin and formamide <91JHC1819>. A similar reaction leads to 5-methylhistamine (243) <8lJHC83l>. 1-Hydroxyimidazoles are accessible in high yield from reaction of nitrosonium fluoroborate with acetonitrile and appropriate alkenes (Scheme 177) <84TL1319>. 

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. 

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. 

Acyl anions (RC(=0)M) are unstable, and quickly dimerize at temperatures >-100 °C (Section 5.4.7). These intermediates are best generated by reaction of organolithium compounds or cuprates with carbon monoxide at -110 °C and should be trapped immediately by an electrophile [344—347]. Metalated formic acid esters (R0C(=0)M) have been generated as intermediates by treatment of alcoholates with carbon monoxide, and can either be protonated to yield formic acid esters, or left to rearrange to carboxylates (R0C(=0)M —> RC02M) (Scheme 5.38) [348]. Related intermediates are presumably also formed by treatment of alcohols with formamide acetals (Scheme 5.38) [349]. More stable than acyl lithium compounds are acyl silanes or transition metal acyl complexes, which can also be used to perform nucleophilic acylations [350],... 

The energetics, too, illustrate the cooperative nature of the two H-bonds. As reported in Table 2.48, the formamide and formic acid molecules are bound together in the cyclic complex by some 12.6 kcal/mol at the MP2/DZP level. The (OH--0) H-bond of structure (b) contributes 7.0 kcal/mol while 3.8 kcal/mol more arises from the (NH"0) interaction. Together, these two separate H-bonds add up to less than the full interaction in the cyclic structure. (Structures (b) and (c) do not represent true minima on the potential energy surface.) It is interesting to note that correlation plays little apparent role in the computed binding energies of this particular complex. 

Substituted quinazolines 49 are conveniently prepared by the action of formamide on 2-aminophenyl alkyl, aryl, and arylalkyl ketones 48 in the presence of boron trifluoride diethyl ether complex as catalyst.This variation gives good yields and cleaner products than the method- in which formic acid is used as catalyst. 

Some of the 4,5-dialkylimidazoIes made by Bredereck [48] are thought to be complexes with formic acid, i.e. the reaction of acetoin with formamide gives a 1 1 hydrogen-bonded adduct of formic acid and 4,5-dimethylimidazole rather than the formate salt, and so an alternative synthesis of 4,5-dimethylimidazole has been proposed using the sequence 4-hydroxymethyI-5-methylimidazole 4-chloromethyl-5-methylimidazole 4,5-dimethylimidazole (80-90%) as the free base [56],... 

The nitrogen atom in a-ferrocenylalkylamines generally shows the same reaction pattern as that in other amines alkylation and acylation do not provide synthetic problems. Due to the high stability of the a-ferrocenylalkyl carbocations, ammonium salts readily lose amine and are, therefore, important synthetic intermediates. Acylation of primary amines with esters of formic acid gives the formamides, which can be dehydrated to isocyanides by the standard POClj/diisopropylamine technique (Fig. 4-16) [92]. Chiral isocyanides are obtained from chiral amines without any racemization during the reaction sequence. The isocyanides undergo normal a-addition at the isocyanide carbon, but could not be deprotonated at the a-carbon by even strong bases. This deviation from the normal reactivity of isocyanides prompted us to study the electrochemistry of these compounds, but no abnormal redox behaviour, compared with that of other ferrocene derivatives, was detected [93]. The isocyanides form chromium pentacarbonyl complexes on treatment with Cr(CO)s(THF) (Fig. 4-16) and electrochemistry demonstrated that there is no electronic interaction between the two metal centres. 

Remko M. Structure and gas phase stability of complexes L-M, where M = Li+ Na, Mg2 and L is formaldehyde, formic acid, formate anion, formamide and their sila derivatives. Mol Phys. 1997 91 929-36. 

Scheme 14 Catalytic hydrogenation of CO2 to formamide and formic acid by iron complex 29 (in situ generated)...

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