Amines protonation shifts

Similar trends arise for protonated amines, although 3 effects and branching corrections are smaller than for the amines. Protonation shifts of primary amines appear to decrease with branching at the cx carbon. 

The close agreement of the three methods supports the contention that protonation at low temperatures first occurs at nitrogen and is followed by a proton shift to give the iminium salt (M). The rate of this rearrangement is dependent on temperature, the nature of the amine, and the nature of the carbonyl compound from which the enamine was made. Even with this complication the availability of iminium salts is not impaired since the protonation reaction is usually carried out at higher temperatures than —70°. Structurally complicated enamines such as trichlorovinyl amine can be readily protonated (17,18). 

The chemical shift of the amine nitrogen is 55 ppm and shows a clear 3-bond correlation to the aromatic proton giving a fine doublet at 7.49 ppm. There is also a strong, and in this case, very useful, 1-bond correlation to this nitrogen from the amine proton itself. Note that whether or not you see 1-bond correlations depends largely on how broad the -NH signal is in the proton domain. The sharper the -NH, the more likely you are to see them. As with 13C HMBC, 2-bond correlations can sometimes be quite weak and that is so in this case as there is no obvious correlation to be seen from the methylene protons adjacent to the amine. 

BioH14 is a mdo-polyborane, therefore, it is expected that it forms adducts with Lewis bases. This is indeed the case but with concomitant loss of hydrogen as shown in Eq. (51). These adducts of the type BioHi2-2L (L = amines, pyridine, phosphines, nitriles, dialkylsulfides inter alia) proved to be versatile reagents. For instance, when triethylamine is used to replace acetonitrile from the adduct not only does the expected replacement occur but in preference also a proton shift (most likely prior to the base displacement reaction) with cluster closure to the decahydro-doso-decaborate(2—) (Eq. 52) ... 

Amino substituents in acyclic derivatives have been discussed by Eggert and Djerassi (396), who emphasize structural and conformational effects, whereas Batchelor has investigated SCS(NH2) and nitrogen protonation shifts in methylated cyclohexylamines (424). The, 3C NMR spectra of amino acids have been compared with those of amines and carboxylic acids (425,426). The transmission mechanisms of amino, ammonium, trimethylammonium, acetamido, and di-acetamido groups have been examined by Faure and co-workers (427), the SCSs of nitro groups by Ejchart (400), and those of azido functions in steroids by Lukacs and co-workers (428). 

In 2003, we reported a multicomponent approach toward highly substituted 2H-2-imidazolines (65) [157]. This 3CR is based on the reactivity of isocyano esters (1) toward imines as was studied in detail by Schollkopf in the 1970s [76]. In our reaction, an amine and an aldehyde were stirred for 2 h in the presence of a drying agent (preformation of imine). Subsequent addition of the a-acidic isocyanide 64 resulted in the formation of the corresponding 2//-2-imidazolines (65) after 18 h in moderate to excellent yield. The mechanism for this MCR probably involves a Mannich-type addition of a-deprotonated isocyanide to (protonated) imine (66) followed by a ring closure and a 1,2-proton shift of intermediate 68 (Fig. 21). However, a concerted cycloaddition of 66 and deprotonated 64 to produce 65 cannot be excluded. 

In our NMR studies 143,147,148,322-324) of amine and other adducts of Ni[R-dtp]2 complexes neat amines were employed in order to eliminate variations in extent of association (H-bonding) of the amines, to permit observation of NH proton shifts, and to maximize the concentration of the preferred adduct. The use of high concentration of primary amines in solutions with Ni[R-dtp]2 complexes can lead to products other than those expected, e.g., with aliphatic diamines, the R-dtp anion salts of f/zs(diamine)nickel(ll) chelates are obtained ). Furlani and co-workers ) have shown that Ni-(ethyl-dtp)2 reacts with n-butyl amine to yield complexes containing the NiS2N4 chromophore, presumably with monodentate ethyl-dtp. In all work with adducts it is necessary to assure that the complexes, adduct molecules and solvent systems are anhydrous. A number of authors 132,284,295,329) shown that Ni[ R-dtp ]2 complexes decompose when in contact with water. 

The orientation of lone electron pairs at heteroatoms can affect H and 13C chemical shifts substantially. This has been studied in conformationally rigid cyclic amines. Protons in piperidines are shielded significantly if they are antiperiplanar to the nitrogen lone pair70-72. 

Diaryl amines, ethers or sulphides, or their aryl vinyl analogues, provide another 6-electron system related to stilbene, but for these a pair of electrons is provided by the single heteroatom (ArXAr or ArXC=C). With dtaryl compounds the initial photocydized product is a zwitterion that undergoes a proton shift to give, for example, N-methyl-4a,4b-dihydrocarbazole from methyldiphenylamine, with subsequent oxidation to N-methylcarbazole (3.74). With the aryl vinyl analogues the product after the proton shift can normally be isolated (3.751. An especially useful variation of this reaction employs... 

Soloshonok and co-workers have developed a method for the synthesis of a-(perfluoro-alkyl)amines from perfluoroalkyl carbonyl compounds by a transamination involving an azomethine a/omethine (Schiffbase) isomerization. They call this method a biomimetic, base-catalyzed 1,3-proton shift reaction, and have applied it to perfluoroaldehydes,12-15 perfluoroalkyl ketones,12 18 / -(perfluoroalkyl)-/l-oxo esters,15 16 19 24 and - -( perfluoroalkyl)-a-oxo es-ters2 " -26 to synthesize the corresponding a-(perfluoroalkyl)amincs, / -(perfluoroalkyl )-/i-amino acids, and 3 -(perfluoroalkyl)- x-amino acids. 

Based on the results described above, the base-catalyzed 1,3-proton shift reaction constitutes a general approach to x-(perfluoroalkyl)amines 17 starting from perfluoroaldehydes and perfluoroalkyl ketones. 

With a primary amine, the initially formed A -nitrosamine can undergo a proton shift by a sequence analogous to interconversion of a ketone to an enol. The product is called a diazoic acid ... 

Proton shift produces a rearranged imine, 3, which can hydrolyze to the keto acid 4. The keto acid is a deamination product. Alternatively, decarboxylation can occur (see Section 18-4) and the resulting imine, 5, can either hydrolyze or rearrange by a proton shift to a new imine, 6. Hydrolysis of 5 or 6 gives an aldehyde and an amine. 

Amination of 5-bromo-l,6-naphthyridine (113) gives as tele product 2-amino-l,6-naphthyridine (51 ),24 but in addition to the intermediacy of anionic cr-adduct (114) (as proved by H-NMR spectroscopy), its formation involves anionic cr-adduct 115, which is formed by a proton shift from 114. The number of atoms between positions 2 and 5 is five, thus this reaction is referred to as an odd tele substitution. Both types of tele substitution involve Addition of the nucleophile as the initial step and Elimination of the leaving group as the last step. However, in the even tele substitution the elimination can be described to take place from a neutral dihydro species, while in the odd tele substitution the elimination must occur from an anionic intermediate. In the naphthyridines several examples of even and odd tele substitutions are found, and in the following sections the results of studies concerned with tele amination are presented. 

The predictions of the proton shifts is difficult the prediction is even more difficult in the case of heteroatoms. In the case of cr spin density like in a aliphatic amine (Table 2.2A), the 13C Fermi contact shift for the a-carbon of the aliphatic amine is upfield (A/h is negative) because of predominant spin polarization effects, whereas that for other carbon atoms is downfield, and rapidly attenuates with the number of bonds. A sizable downfield shift is experienced by the 14N nucleus when nitrogen is a donor atom. 

The search for electrophilic catalysis could in principle be aided by use of tertiary amines as nucleophiles, in which case an intramolecular or solvent assisted proton shift, formulated in [13] and [14], is eliminated. Thus Ayediran, Bamkole and Hirst (1974) studied salt effects on the reactions of 4-fluoro- and 4-chloronitro-benzene with trimethylamine in DMSO, which proceed according to equations (29) and (30). It had been noted (Suhr, 1967) that the... 

The quaternary nitrogen acts as an electron sink, which facilitates the decarboxylation. Further electron and proton shifts produce a Schiff base between the amine and pyridoxal phosphate, which is then hydrolyzed. 

In nonaqueous solvents such as DMSO-d6, complementary nucleosides will form Watson-Crick base pairs that can be monitored by NMR. The spectra of guanosine and cytidine, both separately and together, are shown in Figure 14.27. For guanosine, the observed resonances include Hg at 5 8.6, NH2 at 5 7.2, and the Hr at 5 6.4. For cytidine, the observed resonances are H6 at 5 8.5, NH2 at 5 7.8, H < at 5 6.5, and H5 at 5 6.45. In a 1 1 mixture, the resonances for the amine protons of both the guanosine and cytidine bases are shifted downfield due to hydrogen bond formation. In addition, the... 

The final series of steps are addition of the amine to a carbonyl carbon of a second ninhydrin molecule (1), a proton shift (2), and loss of water to form the purple anion. Notice that the amino nitrogen is all that remains of the original amino acid. 

The shifts of the lamellar-hexagonal transition during titration are greater and in the opposite direction relative to changes of Tm- Thus, for didodecyl PE, the lamellar-hexagonal transition decreases by 41°C during phosphate protonation (pK 1.9) and by 50°C during amine protonation (pK 9.3), whereas for Tm these shifts are 6°C and 15° C, respectively, in the opposite direction (Fig. 3f) (54). 

In contrast to 2, the above derivatives incorporate four hydrogen bond donors. As a consequence, a favourable bonding situation is present in which the four secondary amine protons of each host can interact with the two charged carboxylate groups of the guest - see 4a and 4b. The proposed structure of the complex of the bis-urea derivative was supported by the existence of large NMR downfield shifts for both the inner and outer urea NH resonances in deutero-dimethyl sulfoxide and the observation of intramolecular H NOEs between the receptor aryl and the guest CH2 resonances in this solvent. A Job s plot confirmed the 1 1 stoichiometry of the product. 

The reaction of benzofuroxan with malononitrile and amine catalysis proceeds to give 3-amino-quinoxaline-2-carbonitrile 1,4-dioxide (6). In this case, the primary adduct is stabilized by an intramolecular proton shift rather than by an elimination rcaction. " - Benzimidazoles can also be formed through this reaction (see also Houbcn-Weyl, Vol. E8a, p 303). 

In general, the hydrogen bond produces a spectral shift of the absorbance maximum the addition of proton acceptor compounds to aniline derivatives changes the A.max value and this variation may be used to calculate the extent of association, i.e. the apparent stability constant of the complex amine/proton acceptor in the ground state. The hydrogen bond also causes fluorescence enhancement of the quenching of amines146. 

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