Chemistry of amidines. Part 1. Determination of the site of initial protonation in N′-pyridylformamidines

Abstract

A series of substituted N,N-dimethyl-N'-pyridylformamidines has been synthesised and the pK, values of the conjugate acids have been measured in water at 25°C. Consideration of the pK, values shows that initial protonation is predominantly on the imino nitrogen of the amidine system rather than on the pyridyl nitrogen. The effect of the protonation on the 'H and 13C NMR spectra of the amidines is discussed.In general, protonation of the amidine functional group N=C-N occurs on the imino nitrogen (la) rather than the amino l a l b .N-CHa I CH, X 2 5Me 3 4-Me

Solution Chemistry of N,N’‐Disubstituted Amidines: Identification of Isomers and Evidence for Linear Dimer Formation

“…Additionally, 1 H, 19 F-HOESY (heteronuclear NOESY)e xperiments were performed at À90 8Ct o complete the information about the relative position of the CÀAr, NMes, and NHMes substituents (Figure 6a nd Figure S15 in the SupportingI nformation). Especially in 1,s trong 1 H, 19 Fheteronuclear NOE cross-peaks between the C 6 F 5 groups and one of the mesityl groups of the opposite isomer confirm as tacked arrangement of the aryl rings in 1.I n2,w here the heterodimeric state is less populated, the NOE correlations involving the CF 3 groups are weaker, but confirm the same stacked arrangementasi n1. Especially in 1,s trong 1 H, 19 Fheteronuclear NOE cross-peaks between the C 6 F 5 groups and one of the mesityl groups of the opposite isomer confirm as tacked arrangement of the aryl rings in 1.I n2,w here the heterodimeric state is less populated, the NOE correlations involving the CF 3 groups are weaker, but confirm the same stacked arrangementasi n1.…”

“…[53,54] Diphosphorus pentoxide (21.3 g, 75.0 mmol, 6.0 equiv), hexamethyldisiloxane (26.0 g, 34.2 mL, 160 mmol, 13 equiv) and dichloromethane (30 mL) were heated to reflux for 1h.All volatile compounds were removed by distillation at 165 8C. 19 The combined organic extracts were dried over Na 2 SO 4 ,c oncentrated in vacuo, and filtered over neutral aluminum oxide.…”

“…[6][7][8][9][10][11] For example, the Z isomer is favored as the steric bulk of the substituent R 1 increases. [7,15,[19][20][21][22] On the basis of variousI R measurements it was generally assumed that E/Z isomerization is very unlikely to occur at room temperature, and that rotational isomerism with respect to the CÀNs ingleb ond is the main isomerization process in N,N'-disubstituted amidines. [15] The activation energy for rotation about the C=Nd ouble bond is generally estimated to be too high to occur at room temperature, and hence no equilibrium of E and Z isomers should be operative.…”

“…Experimentally determined rotational barriers for the CÀNb ond are in the range of 50-80 kJ mol À1 . [7,15,[19][20][21][22] On the basis of variousI R measurements it was generally assumed that E/Z isomerization is very unlikely to occur at room temperature, and that rotational isomerism with respect to the CÀNs ingleb ond is the main isomerization process in N,N'-disubstituted amidines. [17,29] The E-syn and Z-anti isomers shown in Scheme 1a re linked by tautomerism, whereas the transfer of the protonf rom one nitrogen atom to the other for the E-anti and Z-syn isomers would only yield the respectivei dentical structures.…”

Reaction of Tosylmethyl Isocyanide with N-Heteroaryl Formamidines: an Alternative Approach to the Synthesis of N-Heteroaryl Tosylimidazoles

“…Accordingly, 2-amino pyridine 1a-c or 2-amino pyrimidine 1d-g were treated with an excess of dimethyl formamide dimethyl acetal (DMFDMA) 2 following the protocol described by Cunningham,14 to give N,N'-dimethyl amino formamidines 3a-g with most yields between 71 and 90% ( Most of the reaction conditions used to generate the carbanion from TosMIC employ a strong base such as sodium hydride or n-butyl lithium.…”