Imine hemi aminal

The heterocyclic hemi-aminal 44 was formed as a model for the synthesis of the marine alkaloids zoanthamine and zoanthenol and is derived from the cyclic imine formed by the reduction of an appropriated substituted azide <07H(72)213>. A pyrrolidine-fused azepine has been isolated from the venom of the ant Myrmicaria melanogaster and assigned as 45 based upon GC and FT-IR comparison with synthetic material <07JNP160>. The axially chiral doubly bridged biphenyl azepine 46 has been synthesised and used with oxone as an epoxidation catalyst in a biphasic system <070BC501>. 

Analysis of DCLs by a combination of high-performance liquid chromatography (HPLC) and MS (LC-MS) has proven very powerful, provided the library members are stable enough to allow chromatographic separation. LC-MS analysis can yield both the quantity and the identity of individual library members. Care should be taken that the exchange between library members is slow on the timescale of the experiment. This is usually the case for hydrazone and disulfide libraries, without requiring special precautions. It has recently been reported that even the composition of DCLs of hydrolytically labile imines can be analyzed directly by HPLC, provided an acidic mobile phase is used. Beau et al. successfully used a common reversed-phase HPLC solvent system based on acetonitrile/water mixtures containing 0.1% trifluoroacetic acid [10]. Imine hydrolysis is slow under these conditions because at low pH the zwitterionic hemi-aminal intermediate that is believed to be important in the hydrolysis process is more difficult to attain (Scheme 2.1). 

Scheme 2.1 The mechanism for imine hydrolysis under acidic conditions is believed to involve the decomposition of the zwitterionic hemi-aminal intermediate as the rate-determining step (10). The rate of...

Pre-forming the electrophilic species in this reaction has greatly increased its utility and the diversity of substrates that have been exploited. Species that have been used include aminal 15, hemi-aminal 16, imine 17, and iminium ion 18. 

Functionalized iminium salts 24 can be readily prepared by a number of methods and allows the reaction to be conducted at lower temperatures and in non-protic solvents thus allowing other, more sensitive active hydrogen species to participate in this reaction. These methods can include alkylation of existing imine 22, cleavage of aminals 25 or hemi-aminals 23 with acetyl chloride or trimethylsilyl iodide/chloride, or in a direct fashion from carbonyl derivative 26 with amine salts or with trimethylsilyl amines. 

As illustrated in O Scheme 65, 33 reacts with an amine to give an imine 326 that isomerizes into an aminoketose 327 (Amadori product), existing as an equilibrium mixture of cyclic hemi-acetals, whereas 40 affords, by way of 328, the hexosamine derivatives 329 and 330 (Heyns products), also in cyclic form The Amadori-He)ms compounds index Amadori-Heyns com-pounds % are at the head of the complex sequences of the Maillard reaction. The crystal structure of the Amadori product 331 between 33 and glycine has been determined more than three decades after the first proposal of its structure. Alternative preparations and X-ray analyses of Heyns products 332 and 333 have been reported [273,274]. 

What determines whether 1,2- or 1,4-additions will take place With the nucleophiles shown, both processes are reversible. Usually the 1,4-products form because they are carbonyl compounds and are more stable than the species arising from 1,2-addition (hydrates, hemi-acetals, and hemiaminals. Sections 17-6,17-7, and 17-9). Exceptions include amine derivatives such as hydroxylamine, semicarbazide, or the hydrazines, for which 1,2-addition eventually leads to an imine product whose precipitation out of solution drives the equilibrium. Once more, the competition between 1,2- and 1,4-addition illustrates Le ChateUer s principle in action, a characteristic of carbonyl chentistty (Sections 18-2 and 18-7). 

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