Basicity aliphatic amines

Sulfonamides (R2NSO2R ) are prepared from an amine and sulfonyl chloride in the presence of pyridine or aqueous base. The sulfonamide is one of the most stable nitrogen protective groups. Arylsulfonamides are stable to alkaline hydrolysis, and to catalytic reduction they are cleaved by Na/NH3, Na/butanol, sodium naphthalenide, or sodium anthracenide, and by refluxing in acid (48% HBr/cat. phenol). Sulfonamides of less basic amines such as pyrroles and indoles are much easier to cleave than are those of the more basic alkyl amines. In fact, sulfonamides of the less basic amines (pyrroles, indoles, and imidazoles) can be cleaved by basic hydrolysis, which is almost impossible for the alkyl amines. Because of the inherent differences between the aromatic — NH group and simple aliphatic amines, the protection of these compounds (pyrroles, indoles, and imidazoles) will be described in a separate section. One appealing proj>erty of sulfonamides is that the derivatives are more crystalline than amides or carbamates. 

The reaction of 2-bromo-5-nitrothiazole with weakly basic secondary aliphatic amines gave the expected 2-amino products. The isomeric 5-bromo-2-nitrothiazole with such amines gave mixtures of the expected 5-amino products along with 2-aminated 5-nitrothiazole rearrangement products. A mechanism was proposed which involves the slow thermal isomerisation of the 5-bromo-2-nitrothiazole to the much more reactive 2-bromo isomer which competes, in the case of relatively weak amine nucleophiles, with direct but slow displacement of the 5-bromo group to form the normal displacement product <96JHC1191>. 

Figure 19. Multifunctional nature of quinine as a catalyst. The various parts of the molecule fill the following roles (a) hydrogen bond forming ligand forming with metals (b) basic amine (c) aliphatic hydrocarbon—bulk (d) handle to modify (e,f) epimers available few conformers (g) aromatic hydrocarbon—bulk, polarizable (h) handle to modify steric and polar influence.

All of these processes are of limited synthetic utility because of the requirement of the use of stoi chiometric amounts of palladium complexes. However, by judicious choice of reactants and condition the above-mentioned impediments to catalysis can be overcome. For example, an efficient palladium(II) catalyzed cyclization of o-allyl- and o-vinyl-anilines to indoles has been developed (equation 14).28 Be cause arylamines are -106 less basic than aliphatic amines, and because the cyclized product in thi system gave an enamine (indole) stabilized by aromatization, the problems of catalyst poisoning by sub strate or product were circumvented, and catalysis was successfully achieved. The system was quit tolerant of a variety of functional groups and was used to prepare indoloquinones in excellent yieli... 

The existence of the alkylamines was predicted by J. von Liebig,1 1837 in 1849, A. Wurtz obtained the primary alkylamines and in 1851, A. W. Hofmann prepared the primary, secondary, and tertiary alkylamines, and also the alkylammonium bases or the quarternary ammonium bases in which all four atoms of the ammonium group are replaced by the alkyl radicles. The basic character of ammonia is retained by the amines, and since the alkyl radicles are themselves basic, the aliphatic amines are even more basic than ammonia itself. W. Ostwald made an estimate of the basicity of the ethyl ammonias, and found the relative strengths of these bases ... 

Amidines and guanidines are slightly more basic than aliphatic amines, and steri-cally crowded amidines (e.g. DBU) or guanidines are often used to mediate dehydro-halogenations. Conditions can, however, sometimes be found which lead to the N-alkylation of these organic bases (Scheme 6.30). Identification of appropriate conditions for such reactions is mostly empirical, because small changes can have important but unforeseeable effects on the selectivity of a reaction (compare, e.g., the first and second reactions in Scheme 6.30). If the reactivity of a given substrate is too low, its nucleophilicity can be enhanced by deprotonation. 

Amides are less basic than amines, and aromatic amines are less basic than aliphatic amines. Therefore, the order is ... 

Since amines are organic bases, water solutions show weakly basic properties. If the basicity of aliphatic amines and aromatic amines are compared to ammonia, aliphatic amines are stronger than ammonia, while aromatic amines are weaker. Amines characteristically react with acids to form ammonium salts the nonbonded electron pair on nitrogen bonds the hydrogen ion. 

Aromatic amines are generally less basic than aliphatic amines.This is true both when the nitrogen atom is part of the aromatic system (as in j pyridine, a hybridization effect), and 1 when the nitrogen atom is bonded to the aromatic ring (as in aniline,... 

Figure 7. Reaction mechanism of a strongly basic amine like an aliphatic amine or hydroxylamine with a carbonyl group (17)...

Sorption of amines on starch was recognized760 as early as 1910 in studies of the interactions between starch and piperidine. Experiments with starch and 1 -butylamine show extraordinarily high and fast adsorption. The equilibrium concentration of that amine reaches 1982 mg/g of starch, as compared to n-hexane (6 mg/g), ethyl acetate (27 mg/g), and ethanol (208 mg/ g). Desorption is, in fact, also significant, but is much lower than in the case of the other complexes just mentioned. Because of their basic properties, amines decompose their host molecule.674 Less-basic amines, such as aromatic trypoflavin761 and aliphatic amine salts,762 can be included into starch. 

Pyridine is weakly basic. It is less basic than aliphatic amines because the lone pair is in an sp rather than an sp- orbital which, with higher s character, is held more closely to the nucleus. Nevertheless, alkyl and reactive aryl halides react with pyridines to form quaternary 7V-alkyl (or A -aryl) salts. 

Aromatic amines are less basic than aliphatic amines and the basicity is influenced by substituents on the aromatic ring. The reactivity of amines is modified by conversion to amides such as acetanilide. These still undergo electrophilic attack in the ortho and para positions. 

A hydrogen-bond basicity scale has been developed that can be used to determine the relative basicity of molecules. Table 8.2 gives the pAinn values for several common heteroatom containing molecules. This is obtained from the protonated form (conjugated acid) of the base in question. The larger the number, the more basic is that compound. The basicity of aliphatic amines has been calculated, the ion-pair... 

The bulk of this Appendix is on acidity because many more functional groups are acidic than are basic. Basically (oooh, sony), only one functional group is basic amines. There is variation among aliphatic, aromatic, and heteroaromatic amines these are covered thoroughly in text sections 19-5 and 19-6. One point in the text. Just before Table 19-3, deserves emphasis for any conjugate acid-base pair ... 

The lone pair of electrons on the nitrogen atom of aminobenzene (or aniline) can be stabilised by the delocalisation of the electrons onto the 2-, 4- and 6-positions of the benzene ring. Aromatic amines are therefore less basic than aliphatic amines. 

As the lone pair is part of the aromatic sextet it is less nucleophilic/basic than aliphatic amines... 

High trimerization rates have also been observed in the presence of basic catalysts. Aliphatic and heteroaromatic amines, alkali hydroxides and alkali alkoxides have been used.247 249,256 The base presumably adds to the carbon atom of the cyanate group, and then the adduct takes part in the trimerization reaction.257 Pyridines and derivatives are superior in catalytic activity compared to tertiary alkylamines. 

Thiadiazolophthalazine (468) treated with sufficiently basic primary aliphatic amines (e.g., methyl-amine or ethylamine) provides high yields of triazolo analogs (469) (Equation (73)) <94PHA489>. 

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