Amines and amide ions

The only reaction of this type mentioned in CHEC-I is the formation of 3-AT-benzoyl-anilinopyridazine from pyridazine A-oxide and A-phenylbenzonitrilium ion 84CHEC-l(3B)l . 

4-Nitro-, 3-aryl-5-nitro- and 3,6-diaryl-4-nitropyridazines react almost instantly in liquid ammonia to give the 4(or 5)-c7-adducts while 5-cyano-3-aryl- and 4-cyano-3,6-diarylpyridazines require the addition of amide ion for the initial amination reaction (Equation (7)). Both types of adduct can be oxidized to give the 4(or 5)-aminopyridazine derivatives and NMR studies with the nitro and cyano derivatives show conclusively that amination occurs at the 4- or 5-positions 88JHC831 . 

5-dihydro-4-hydrazino-3(2//)-pyridazinones have been identified as byproducts in the reactions of 

6-substituted-3(2//)-pyridazinones 84H(22)i80i, 89H(29)1077 . The direct amination has been observed before 72JCS(P1)1483 but occurred with 6-hydrazino- and 6-methoxy-3(2//)-pyridazinones formed in situ from 3,6-dimethoxypyridazine, and the site of amination was incorrectly assigned 74JCS(Pl)696 . This work has been corrected 93H(35)1313 . 

Under the alternative low-temperature procedure, animation is conducted in liquid ammonia. The use of KNH2, which is more soluble than NaNH2 in this solvent, is preferable. The reaction occurs under homogeneous conditions and does not show the previous dependence on substrate basicity. Diazines, triazines, and tetrazines, which usually undergo destruction in the high temperature process, are aminated successfully in liquid ammonia. 

In liquid ammonia, hydride ion, which is a very poor leaving group, cannot eliminate spontaneously. An oxidant (KN03 or better KMn04) is usually added to aromatize the cr-complex (B-94MI502-06). 

In the animation of quinoline in liquid ammonia, the initially formed cr-complex (242) on heating is fully isomerized to the more stable cr-complex (243). This transformation is used in preparative work. Adding potassium permanganate to the cr-complex formed under kinetic or under thermodynamic control allows either 2-amino- or 4-amino-quinoline to be obtained in good yield. 

Of all the aza-heterocycles, pyridine possesses the least electron deficiency. Because of this, pyridine itself does not form a a-complex in liquid ammonia and cannot be aminated under these conditions. By the contrast, highly ir-deficient polyaza-heterocycles (diazines, triazines, tetrazines, pteridines, etc.) undergo oxidative amination, sometimes even by liquid ammonia itself. Sodamide converts 4-methylpyrimidine successively into the 2-mono- and 2,6-di-amino derivatives, and pyrazine gives 

2- aminopyrazine. Nitro groups, the activating ability of which is even stronger than that of an aza-group, facilitate the amination. For instance, 4-nitroquinoline on treatment with liquid ammonia and KMn04 at — 33°C gives 3-amino-4-nitroquinoline in 86% yield. 

---

Hydroxide ion and other O-nucleophiles Amines and amide ions S-Nucleophiles Halide ions Carbanions... 

The commonest of these for oxirane opening are amines and azide ion [amide ions promote isomerization to allylic alcohols (Section 5.05.3.2.2)]. Reaction with azide can be used in a sequence for converting oxiranes into aziridines (Scheme 49) and this has been employed in the synthesis of the heteroannulenes (57) and (58) (80CB3127, 79AG(E)962). 

Importantly, unmodified PAMAM and PPI dendrimers have functional groups within their interior as well as on their exterior. Specifically, PAMAM dendrimer interiors contain both tertiary and secondary (amide) amines, and both of these are ligands for many metals [19,82,83,87,89]. For example, Turro et al. [87, 89] investigated the binding of Cu + ions to integer and half-integer PAMAM dendrimers. Their EPR results indicated that Cu + can bind to both exterior acid and amine groups, as well as to interior tertiary amines and amides. Similarly, PPI dendrimers have interior tertiary amines and are also able to bind metal ions, such as Cu +, Zn +, and Ni + within their interior [90,100]. 

Twelve volatile acyclic amines and amides (114-120,125-129) (Table VIII) from ponerine ants in the genus Mesoponera have been identified by gas chromatography-mass spectrometry and mass spectral comparison with authentic synthetic samples 41). The major aliphatic amine, A-isoamylnonylamine (114), shows a molecular ion at m/z 213, a-cleavage fragments at miz 156 (M — C4H9)... 

A glance at the pKa values in Table 3.1 reveals that many classes of compounds can act either as acids or as bases, depending on the reaction environment. Such materials are termed amphoteric. They must have an acidic proton (i.e., a proton attached to an electronegative element or group) and unshared pairs of electrons that can be donated to a proton. For example, water, alcohols, and other hydroxylic compounds as well as amines and amides are all amphoteric materials. Comparing the p.Ka s of these materials permits an assessment of the predominant behavior in a given environment. For example, if an amine is dissolved in water, it could function as an acid or a base. To determine which behavior will predominate, the position of the equilibrium can be determined for each process. Comparison of these values will indicate which will be the principal behavior. Thus, as an acid, the amine would donate a proton to water to give an amide anion and the hydronium ion. 

Photoelectron spectroscopy (ESCA) and thermal evolved gas analysis (EGA) have been applied to characterize sulfur- and nitrogen-containing species in atmospheric particulate matter. Particulate amines and amides previously identified only by ESCA have been detected by EGA, a bulk method, for the first time. EGA and ESCA results suggest the existence of a sulfate similar to ammonium sulfate but with some of the ammonium ions replaced by a charged organic nitrogen complex. 

Amines and amides are classified as primary, secondary, tertiary, or quaternary depending on the number of bonds from nitrogen to carbon(Following fig.). Note that a quaternary amine is positively charged and is therefore known as a quaternary ammonium ion. It is not possible to get a quaternary amide. 

Fig. Destabilising inductive effect of the ethoxide ion. Amines and Amides...

Both Siegel et al. (122) and Lawrence et al. (123) have described automated systems for the purification of small arrays of amines and amides. A 48-member array of P-amino alcohols prepared from epoxides and amines was purified using SPE by Shuker et al. (124). Blackburn et al. (125) have described the purification of a 60-member 3-aminoimidazo[l,2-fl]pyridine array obtained from a multiple-component condensation, and Bussolari et al. (126) purified a small array of phenylpropyl amines obtained from dihydrocoumarins and amines. A few applications where ion-exchange resins have been substituted with other solid phases have also recently appeared. For example, the purification of several carbohydrate arrays tagged as hydrophobic O-laurates using Ci8 silica producing up to 10-30 mg of >90% pure individuals was described by Nilsson et al. (127), and Curran et al. purified fluorous-... 

---