Amines shifts

Table 8 illustrates the technique using a series of racemic amines. Shift differences are quite large (and are very similar for esters which are not shown) and comparable to the effects of the Alexakis Reagent. 

Any structural feature that stabilizes the ammonium ion (relative to the free amine) shifts the reaction toward the right, making the amine a stronger base. Any feature that stabilizes the free amine (relative to the ammonium ion) shifts the reaction toward the left, making the amine a weaker base. 

It is interesting to note that the reaction does not take place with aromatic amines, whose basicity is not strong enough. In another respect, Mn + can be replaced by Fe + in order to carry out the reaction.) Evidently, the amine shifts the equilibrium of the redox reaction toward the right. Concerning this point, we ll also mention the fact that the reaction only occurs at neutral or weakly alkaline pH values. 

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. 

An example of enhanced ion production. The chemical equilibrium exists in a solution of an amine (RNH2). With little or no acid present, the equilibrium lies well to the left, and there are few preformed protonated amine molecules (ions, RNH3+) the FAB mass spectrum (a) is typical. With more or stronger acid, the equilibrium shifts to the right, producing more protonated amine molecules. Thus, addition of acid to a solution of an amine subjected to FAB usually causes a large increase in the number of protonated amine species recorded (spectrum b). 

The tertiary amine is formed in a similar manner from the imine and a secondary amine. This side reaction can be minimized by carrying out the hydrogenation in the presence of ammonia, which tends to shift the equiHbrium back towards the imine. When a compound with two or more nitrile groups is hydrogenated, the formation of both cycHc and acycHc secondary and tertiary amines is possible, depending on whether the side reaction is intramolecular or intermolecular. For example, for the hydrogenation of adiponitfile ... 

A further strong bathochromic shift is observed as the basicity of the primary amines is increased by A/-alkylation, eg, malachite green [569-64-2] Cl Basic Green 4, =621 nm (5). 

The shade may be varied by choosing amines. For aromatic amines, the steric effect of substituents in the ortho position reduces the conjugation of the anibno group with the anthraquinone moiety, and the result is a hypsochromic shift and brighter shade. Thus Cl Acid Blue 129 (120) has a more reddish and brighter shade than Cl Acid Blue 25 (118). Cycloalkylamines have a similat effect on the shade. Cl Acid Blue 62 [5617-28-7] (125) Cl 62045) is an example. 

A nitrogen atom at X results in a variable downfield shift of the a carbons, depending in its extent on what else is attached to the nitrogen. In piperidine (45 X = NH) the a carbon signal is shifted by about 20 p.p.m., to ca. S 47.7, while in A-methylpiperidine (45 X = Me) it appears at S 56.7. Quaternization at nitrogen produces further effects similar to replacement of NH by A-alkyl, but simple protonation has only a small effect. A-Acylpiperidines show two distinct a carbon atoms, because of restricted rotation about the amide bond. The chemical shift separation is about 6 p.p.m., and the mean shift is close to that of the unsubstituted amine (45 X=NH). The nitroso compound (45 X = N—NO) is similar, but the shift separation of the two a carbons is somewhat greater (ca. 12 p.p.m.). The (3 and y carbon atoms of piperidines. A- acylpiperidines and piperidinium salts are all upfield of the cyclohexane resonance, by 0-7 p.p.m. 

Another example of a stereoelectronic effect is observed in amines. Amines in which a C—H bond is oriented antiperiplanar to the nitrogen lone pair show a shift in the C—H bond stretching frequency that corresponds to a weakening of the bond by about... 

Deamination of the corresponding amine gives the allylic alcohol resulting from iQ dride shift as the main product and an increased amount of the cyclization product. 

The reaction produces additional hydrogen for ammonia synthesis. The shift reactor effluent is cooled and tlie condensed water is separated. The gas is purified by removing carbon dioxide from the synthesis gas by absorption with hot carbonate, Selexol, or methyl ethyl amine (MEA). After purification, the remaining traces of carbon monoxide and carbon dioxide are removed in the methanation reactions. 

In the case of substances whose structures are pH-dependent (e.g. phenols, carboxylic and sulfonic acids, amines etc.) it is possible to produce fluorescences or make them disappear by the deliberate manipulation of the pH [213] (Table 20). Shifts of the positions of the absorption and emission bands have also been reported. This is particularly to be observed in the case of modified silica gels, some of which are markedly acidic or basic in reaction (Table 25). 

The present authors have found that the preparation of 7V-acetyl aziridine derivates provides the most secure method of differentiating aziridines from primary amines which are alternate reaction products in a number of cases. The infrared spectra of the former derivatives show only a peak at 1690 cm" for a tertiary amide peaks at ca. 3440 and 1530 cm" indicative of a secondary amide are absent. Acetylation also shifts the aziridine ring protons to a lower field in the NMR by ca. 1 ppm relative to the parent aziridine. The A"-acetyl aziridines are hydrolyzed with 3% methanolic potassium hydroxide. " Published NMR spectra of several 16j5,17j -aziridines reveal resonance patterns resembling those of the respective epoxides. " ... 

The enamines in which the protonation at the -carbon atom is not allowed due to the lack of coplanarity, or, in other words, the lack of electronic overlap, do not exhibit this characteristic absorption shift. For instance in the case of neostrychnine (134) where the overlap is not permitted since this would involve the formation of a double bond at the bridgehead, there is no appreciable difference in the C—C stretching region of the free amine and its perchlorate salt they absorb at 1666 cm and 1665 cm , respectively (70). 

The introduction of a double bond in conjugation with the nitrogen atom fcsults in a bathochromic shift. For instance, in contrast with the saturated amines (A ,, —215 mp, e — 3000), the enamines show a maximum at... 

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). 

Similar behavior can be observed even in the case of substituted quinuclideines 170). Neostrychnine (68) serves as an example of more complex compounds which show spectra differing from those of other enamines. The ultraviolet spectrum of this compound exhibits no batho-chromic shift and its basicity is considerably decreased 159,171,172) (pK in methylcellosolve at 20° is 3.8, whereas the analogous saturated compound has a pK under the same conditions of 7.45, and a compound with the double bond further removed, strychnine, has a pK of 7.37). As another example, the ultraviolet spectrum of trimethyl conkurchine (69) shows the same absorption maxima as a saturated tertiary amine (A in ether, about 213 m/i). 

Enamines in which the double-bond shift is sterically prevented afford only the ammonium salts. Their spectra in the C=C stretching vibration region does not differ greatly from that of the free amine spectrum (171). For example, neostrychnine (159) has vc c 1666 cm and its perchlorate at 1665 cm . Salts of quinuclideine (92) and the polycyclic alkaloid trimethylconkurchine have similar properties. 

In the UV spectrum of the protonation products there is a hypsochromic shift of the absorption maximum of enyne system compared to the bases (74DIS) this agrees with the data of the protonation of simple enamines and dienic amines (69MI1). 

Another pathway for the aromatization of the cr -adducts was found in the reactions of 3-pyrrolidino-l,2,4-triazine 4-oxide 81 with amines. Thus the treatment of 1,2,4-triazine 4-oxide 81 with ammonia leads to 5-amino-1,2,4-triazine 4-oxides 54—products of the telesubstitution reaction. In this case the cr -adduct 82 formed by the addition of ammonia at position 5 of the heterocycle undergoes a [l,5]sigmatropic shift resulting in 3,4-dihydro-1,2,4-triazine 83, which loses a molecule of pyrrolidine to yield the product 54. This mechanism was supported by the isolation of the key intermediates for the first time in such reactions—the products of the sigmatropic shift in the open-chain tautomeric form of tiiazahexa-triene 84. The structure of the latter was established by NMR spectroscopy and X-ray analysis. In spite of its open-chain character, 84 can be easily aromatized by refluxing in ethanol to form the same product 54 (99TL6099). 

A detailed study of spectra of compounds 1, 2, and 3 has been published as part of a general study of azolopyridines (84OMR209). The shifts are shown in Table III. The N shifts have been used to determine the structure of 7-amino-triazolopyridines 128 and 129 (89T7041). The shifts recorded were 56.8, 56.2 (Nl), 245.4, 246.3 (N2), 320.6, 316.8 (N7a), all from nitromethane as standard at 380 ppm the absorption for the amine was at 345.5, 350 ppm in accordance with the amino structure shown, rather than the imino forms 128a and 129a. 

Together with a shift of the proton from the a-carbon to the alkoxide oxygen, the tertiary amine is eliminated from the addition product to yield the unsaturated product 3. Early examples of the Baylis-Hillman reaction posed the problem of low conversions and slow reaction kinetics, which could not be improved with the use of simple tertiary amines. The search for catalytically active substances led to more properly adjusted, often highly specific compounds, with shorter reaction times." Suitable catalysts are, for example, the nucleophilic, sterically less hindered bases diazabicyclo[2.2.2]octane (DABCO) 6, quinuclidin-3-one 7 and quinuclidin-3-ol (3-QDL) 8. The latter compound can stabilize the zwitterionic intermediate through hydrogen bonding. ... 

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