Amidines, cyclic, basicities

A -Imidazolines (294 Z = NH) are cyclic amidines and exhibit the characteristic resonance stabilization and high basicity. A -Oxazolines (294 Z = 0) are cyclic imino ethers, and A"-thiazolines (294 Z = S) are imino thioethers both are consequently easily hydrolyzed by dilute acid. 

A few scattered examples of hexahydro- and octahydro-l,3-diazocines have been reported, mainly in the context of studies on the effect of chain length on the cyclization of diamines. Reaction of the N- aryl-iV - aroyldiamines (194) with polyphosphoric ester gives the cyclic amidines (195) (77JCS(P2)2068). Yields of the diazocines (195 n =5) were about 40%, compared to 90% for the 1,3-diazepine (195 n =4). The basicities of the products decrease in the order of ring size 6 7>8 5, lower basicity reflecting non-planarity of the amidine system. 

Imidazoline is a simple cyclic amidine and its pKaH value is just what we expect, around 11. Imidazole, on the other hand, is less basic (p.fQtH 7.1) because both nitrogens are attached to an electron-withdrawing sp2 carbon. However, imidazole, with its two nitrogen atoms, is more basic than pyridine (pKaH 3.2) because pyridine only has one nitrogen on which to stabilize the positive... 

Imidazolines can exist as three possible structures 2-imidazolines (171), 3-imidazolines (172) or 4-imidazolines (173) (Scheme 83). The first-named can exist as a pair of tautomers, but any proton shift in (172) will give (173) by rearrangement. In fact the hydrolysis of Af-unsubstituted 3-imidazolines to a-aminoketones occurs presumably via the 4-imidazoline. 2-Imidazolines are cyclic amidines, and as such exhibit the characteristic resonance stabilization and strongly basic natures of these compounds. Protonation occurs on the unsubstituted nitrogen to give a resonance-stabilized imidazolinium ion. Examples of p/fa... 

The influence of the aryl substitution for derivatives bearing the aryl group at the functional carbon depends on the electronic nature of the aryl substituent. Smaller basicity is measured than for acetamidines. Bicychc amidines show larger basicity, compared to the most of simple alkyl derivatives, with the gas phase basicities in the following order DBU > DBD > PMDBD > DBN > 74. DBU has the largest gas phase basicity value of 243.4kcalmol . Five-membered ring amidines display smaller basicity than six- and seven-membered cyclic amidines. 

Cyclic amidines are prepared by alkylation of acylic amidines [16]. Bromoamination of olefins by A-bromosuccinimide (NBS) and cyanamide (NH2CN) affords p-bromoalkyl-cyanamides. Chemoselective hydrogenation of the nitrile function leads to acyclic amidines followed by spontaneous cyclization to yield cyclic amidines, which are hydrolyzed under basic condition to give 1,2-diamines (Scheme 3.5). 

A sequence of hydrobenzamide-amarine-isoamarine (8) is one of the useful synthetic routes for C2-symmetric 1,2-diamines through cyclic amidines (Scheme 3.8). The reaction course is proposed as follows (i) formation of hydrobenzamide from benzaldehyde and ammonia, (ii) trimeric condensation to amarine, and (iii) isomerization to isoamarine (8) under basic condition [20] (path A). Corey and Kuhnle [21] proposed an alternative path for the reaction course (path B) based on characterization of each intermediate. This amidine is found to be rather stable to acid-catalysed hydrolysis. Thus, reduction of isoamarine (8) to imidazolidine with aluminum amalgam in wet tetrahydrofuran (THE) followed by acid hydrolysis yields the corresponding 1,2-diamine. 

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