Amidines rearrangement

The amidine rearrangement of N-alkyl-2-iminopyridines into 2-alkyl-aminopyridines (Scheme 1.9). In this rearrangement bond breakage occurs... 

Brown, D. J. Amidine rearrangements (the Dimroth rearrangements). Mech. Mol. MIgr. 1968,1, 209-245. 

The N —> N type isomerization as a special version of the amidine rearrangement was described for the 2-arylaminotetrahydro-l,3-diazepine system 102176. The reaction occurred under neutral conditions to form the rearranged products 103 in 24-83% yields (equation 42). 

The mesylamides of the 2-arylimino-l,3-thiazolines and -thiazines 104 undergo a thermal isomerization similar to the amidine rearrangement to form the iV-mesylanilines 105 by N —> N shift of the mesyl group as a cation but not as a free radical182 (equation 43). 

The iV-acyl ureas 157, prepared by amidine rearrangement (Section II.B.3), undergo thermal elimination of phenyl isocyanate with formation of the amides 158 (Eq. (24)) (01JCS(P1)680). This approach provides access to amides of unstable 2-aminofurans that cannot be prepared by acylation of the primary amine. 

Despite this limitation, Esser and coworkers have managed to demonstrate the applicability of this 1,3-aryl migration, under neutral or basic conditions, in a synthesis of 2-arylamino-4,5,6,7-tetrahydro-l//-l,3-diazepines (51) (Scheme 18.10) [31], Mechanistic studies on this amidine rearrangement in which a 1 1 mixture of two different rearrangement precursors (i.e., 50) was reacted showed no evidence of intermolecular aryl transfer, thus providing evidence for an intramolecular transformation that, in comparison to the Chapman rearrangement, should proceed via a spirocyclic intermediate such as 52. 

A different type of rearrangement occurs when suitable side chains are a to a pyridine-like nitrogen atom. In the monocyclic series this can be generalized by Scheme 43. For a given side chain the rate of rearrangement is l,2,4-oxadiazoles>isoxazoles> 1,2,5-oxadiazoles. Typical side chains include hydrazone, oxime and amidine. Some examples are shown in Table 9 (79AHC(25)147). Similar rearrangements for benzazoles are discussed in Section 4.02.3.2.4. 

Neither the oxide nor the amidine function are in fact required for activity. Treatment of the oxime, 7, with chloro-acetyl chloride in the presence of sodium hydroxide proceeds directly to the benzodiazepine ring system (14)(the hydroxyl ion presumably fulfills a role analogous to methylamine in the above rearrangement). Reduction of the N-oxide function of 14 leads to diazepam (15). ... 

In warm acetonitrile 7-piperidino-3-trityl-3i/-azepine (22) rearranges in high yield to the isomeric 3//-azepine 23.64 The corresponding 2-(pyrrolidin-l-yl) and 2-morpholino derivatives behave similarly. Presumably, the gain of amidine resonance energy in tautomer 23 is the driving force behind this rearrangement. 

Dibenzo[l,3]diazepines 9, together with amidines and benzimidazoles, are produced by a rearrangement reaction when certain A.A -diarylamide oximes 7 are treated with tosyl chloride. The intermediate 0-tosyl derivatives 8 cannot be isolated.176... 

Mesylation of a-amino nitrones (253) in dichloromethane gave amidines (254) via a 3,3-sigmatropic rearrangement (Scheme 2.93) (351). 

Fivefold degenerate reversible [3,3]-sigmatropic shifts were first reported in 1988116,117 in the CPD-amidine system 257, where AG g = 117 to 120 kJmol-1 (equation 88) (for aza-Cope rearrangements see Section IV.E.2). In addition, a slow accumulation of a colored by-product was observed at elevated temperatures. This was identified as a product of a novel intramolecular carbon to nitrogen 1,4-shift of the methoxycarbonyl... 

The reaction depicted in equation 43 between a nitrile and a lithium amide takes place as a 1,2-addition to the cyano group. The product crystallizes as a dimer (236) in which the lithium atoms are solvated by nitrile molecules and differently bonded to the amidine moieties, as shown by XRD analysis. Low-temperature H NMR spectrum in solution points to uniform chemical environments for both the aryl groups and for the Me—Si groups, and to rapid rearrangement of the Li—N coordination structures. Acidolysis of the dimer in solution yields the corresponding amidine (237) . The crystal structure of the THF-solvated analog of 236 shows dissimilar N—Li bond lengths for the two Li atoms... 

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