Substituents amino

The same 3-amino substituent is reactive in condensation reactions (Scheme 235) (701, 726-729). 2-Imino-3-amino-4-thia2oiine reacts, however, in the nicotinoylation reaction through its imino nitrogen (727). 

Pyridine and its methyl derivatives, (2), (3), and (4), undergo amination with sodium amide at the 2-position eg, 2-anTino-3-methylpyridine [1603-40-3] and 2-anTino-5-methylpyridine [1603-41 -4] from (3) (eq. 3). This Chichibabin reactionis most important for introduction of a 2-amino substituent, which may be replaced readily by many other groups (18). 

As might be expected from a consideration of electronic effects, an amino substituent activates pyrazines, quinoxalines and phenazines to electrophilic attack, usually at positions ortho and para to the amino group thus, bromination of 2-aminopyrazine with bromine in acetic acid yields 2-amino-3,5-dibromopyrazine (Scheme 29). 

Amino substituents also behave normally with electrophiles, being acylated and converted to benzylidene derivatives. A-Amino groups have also been converted to benzylidene derivatives and are removed on treatment with A-nitrosodiphenylamine (79JHC249). 

A related diazotization reaction involving the supposed peri-aminolepidine (357) to give the unknown phenalene type system (297) was later shown to be incorrect due to wrong orientation of the amino substituent (42JA2417). 

A kind of modification of the Polonovski-Boon synthesis is the reaction of 5,6-dihalopyrimidines with ethylenediamine derivatives. Depending on the bulkiness of the amino substituents a more or less regiospecific condensation may proceed (71CB780), as shown recently in the reaction of 5-bromo-6-chloro-l,3-dimethyluracil (279) with 2-methyl-amino- -propylamine to form l,3,5,6-tetramethyl-5,6,7,8-tetrahydrolumazine (280 equation 99) (80Ba3385). 

Oxadiazoles are difficult to alkylate, unless the ring contains a strong electron donor group such as an amino substituent. 

Substituted pyrazoles are formylated (Vilsmeier-Haack reaetion) and aeetylated (Friedel-Crafts reaction) at C-4 (B-76MI40402). Both hydroxy and amino substituents in positions 3 and 5 facilitate the reaetion (80ACH(105)127,80CHE1), but the heteroatoms eompete with the C-substitution. For instanee, when the amino derivative (91 R = = Ph, R = H)... 

Amino substituents on a carbon-carbon double bond enhance the nucleophilicity of the p carbon to an even greater extent flian the hydroxyl group in enols. This is because of the greater electron-donating power of nitrogen. Such compounds are called enamines. ... 

Secondary amines cannot form imines, and dehydration proceeds to give carbon-carbon double bonds bearing amino substituents (enamines). Enamines were mentioned in Chapter 7 as examples of nucleophilic carbon species, and their synthetic utility is discussed in Chapter 1 of Part B. The equilibrium for the reaction between secondary amines and carbonyl compounds ordinarily lies far to the left in aqueous solution, but the reaction can be driven forward by dehydration methods. 

The effect of the bond dipole associated with electron-withdrawing groups can also be expressed in terms of its interaction with the cationic u-complex. The atoms with the highest coefficients in the LUMO 3 are the most positive. The unfavorable interaction of the bond dipole will therefore be greatest at these positions. This effect operates with substituents such as carbonyl, cyano, and nitro groups. With ether and amino substituents, the unfavorable dipole interaction is overwhelmed by the stabilizing effect of the lone-pair electrons stabilizing 3. 

Reductive deamination of primary arylamines The amino substituent of an arylamine can be replaced by hydrogen by treatment of its derived diazonium salt with ethanol or with hypophosphorous acid. 

If the structure of the dianil is as shown (58) this is a rare example of initial attack taking place at the 4-amino substituent. 

There has been considerable interest recently in the quatemization of purine compounds, although most of those examined have contained hydroxyl or amino substituents and therefore products may be regarded as the acid salts of N-alkylated derivatives. 

Reactivity in this ring system is sufficient for facile hydrolysis (20°, 2 hr or 100°, 1 min) of the 2-, 4-, 6-, and 7-methoxypteridines in high yield and for easy substitution (75-90% yields) of the 7-methylthio group with methanolic hydrazine hydrate (65°, 15 min), dimethylamine (65°, 30 min), and ethanolic ammonia (125°, 6 hr). The 7-acyloxy intermediate in thionation of 7-oxopteridine with phosphorus pentasulfide is readily substituted (80°) to form pteridine-7-thione. The chloro group in 6-aryl-2,4-diamino-7-chloro-pteridine still reacts readily with hydrazine (100°, several minutes) in spite of the two deactivating amino substituents. 

Derivatives of nalidixic acid (69a-69d), containing an amino or acetyl-amino substituent at position 7 and an alkyl group at N-1, were successfully nitrated to give (70a-70d). However, in all cases hydrolysis of the amino and acetylamino group was observed (79YZ155 80CPB235). 

One further point inductive effects and resonance effects don t necessarily act in the same direction. Halogen, hydroxyl, alkoxyl, and amino substituents, for instance, have electron -withdrawing inductive effects because of the electronegativity of the -X, -O, or —N atom bonded to the aromatic ring but have resonance effects because of the lone-pair electrons on those same —X, -O, or —N atoms. When the two effects act in opposite directions, the stronger of the two dominates. 

Amines with more than one functional group are named by considering the -NH2 as an amino substituent on the parent molecule. 

The mechanism of decarboxylation of acids containing an amino substituent is further complicated by the possibility of protonation of the substituent and the fact that the species NH2ArCOOH is kinetically equivalent to the zwitterion NHj ArCOO. Both of these species, as well as the anion NH2 ArCOO" and even NH3 ArCOOH must be considered. Willi and Stocker644 investigated by the spectroscopic method the kinetics of the acid-catalysed decarboxylation of 4-aminosalicyclic acid in dilute hydrochloric acid, (ionic strength 0.1, addition of potassium chloride) and also in acetate buffers at 20 °C. The ionisation constants K0 = [HA][H+][H2A+] 1 (for protonation of nitrogen) and Kx = [A"][H+] [HA]-1, were determined at /i = 0.1 and 20 °C. The kinetics followed equation (262)... 

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