Double imine

The metal-free imination, as well as the Rh and Ag catalyses, can be applied to the conversion of sulfides into sulfilimines such as 22 and 23 [24]. Unfortunately, however, double iminations leading to sulfondiimides (N-protected forms of 24) did not occur, and compounds such as 25 [27] still require the intermediacy of sulfondiimide 24. Thus, its preparation was achieved by treatment of the corresponding sulfide with a mixture of ammonia and t-butyl hypochlorite [28]. 

Fig. 9.27. Condensation of diamines with dicarbonyl compounds (and/or their hydrates) to give N heterocycles. Double imine formation yields quinoxalines (B), double enamine formation leads to dimethylpyrrole (D).

The product is a highly unstable double imine. Aromaticity is immediately restored and a series of proton shifts and C-N bond formation and cleavage give the aromatic indole. In the last diagram the ten-7t-electron indole is outlined in black. 

The use of TiCl4 did not facilitate the cyclisation and led to the formation of a double imine consuming 2 eq. of fi. Accordingly, primary amines form in the presence of TiCl4 the corresponding imines 8 and the same result is obtained when iminophosphoranes are applied (Scheme 31). 

Figure 4.3 Supported metal complexes based on silicas chemically modified with a double imine...

Dicarbonyl compounds and 1,2-diaminoethanes cyclocondense (with double imine formation) to afford 2,3-dihydropyrazines 20 which are conveniently oxidized to pyrazines 21 by CuO or Mn02 in KOH/ethanol ... 

A double imine formation. Such a process may be carried out without catalysis, but mild acid is usually helpful. The mechanism for the first condensation is shown in detail, the second in abbreviated form. 

Formation of pyrazines and quinoxalines has been a focal point of many years of study. The most common method to make these rings relies on the condensation of 1,2-diamines with 1,2-dicarbonyls in ethanol or acetic acid in 35-85% yields. The mechanism proceeds through a double imine formation. Recently improved methods have been reported, employing transition-metal catalysis and microwaves. ... 

One specialized and readily available carbodiimide, called dicyclohexyl-carbodiimide (usually abbreviated DCC), will be used to illustrate this transformation it has structure 78. Use of this reagent to form esters led to the discovery that adding a catalytic amount of an amine base gives higher yields. This observation will be used, but will not be explained further in this discussion. When 3-methylbutanoic acid (77 isobutyric acid) is stirred with tert-butanol in the presence of a catalytic amount of 4-pyrrolidinopyridine (79), for example, er -butyl 3-methylbutanoate (80) is isolated in 65% yield. In addition to the ester, one molar equivalent of dicyclohexyl urea (see 87) is also isolated. The mechanism that explains these results begins by noting that the diimide carbon in 78 is like a double imine and bond polarization makes the central carbon atom very electrophilic. 

The mechanism proposed for this complex transformation is summarized in Scheme 1.44. It involves the initial reaction between 2,3-diaminomaleonitrile and two molecules of the carbonyl compound, yielding a double imine. The monoamine tautomer of this intermediate imdergoes an intramolecular cyclization that affords iminium derivative 80, which reacts with the isonitrile to give 81. A hydrolysis step affords the final product 79 [65],... 

Primary and secondary amines also react with epoxides (or in situ produced episulfides )r aziridines)to /J-hydroxyamines (or /J-mercaptoamines or 1,2-diamines). The Michael type iddition of amines to activated C—C double bonds is also a useful synthetic reaction. Rnally unines react readily with. carbonyl compounds to form imines and enamines and with carbo-tylic acid chlorides or esters to give amides which can be reduced to amines with LiAlH (p. Ilf.). All these reactions are often applied in synthesis to produce polycyclic alkaloids with itrogen bridgeheads (J.W. Huffman, 1967) G. Stork, 1963 S.S. Klioze, 1975). 

Allylic phosphates are used for carbonylation in the presence of amines under pressure. Carbonylation of diethyl neryl phosphate (389) affords ethyl homonerate (390), maintaining the geometric integrity of the double bond[244]. The carbonylation of allyl phosphate in the presence of the imine 392 affords the /3-lactam 393. The reaction may be explained by the formation of the ketene 391 from the acyl phosphate, and its stereoselective (2 + 2] cycloaddition to the imine 392 to give the /3-lactam 393(247],... 

Carbon—nitrogen double bonds in imines, hydrazones, oximes, nitrones, azines, and substituted diazomethanes can be cleaved, yielding mainly ketones, aldehydes and/or carboxyHc acids. Ozonation of acetylene gives primarily glyoxal. With substituted compounds, carboxyHc acids and dicarbonyl compounds are obtained for instance, stearoHc acid yields mainly azelaic acid, and a smaH amount of 9,10-diketostearic acid. 

Azomethines add with great ease and stereospecificity to carbon-carbon double bonds affording pyrazolidines. They also add to carbon-carbon triple bonds with the formation of pyrazolines. Benzimidazolium iV-imines, e.g. (622), are a special case of azomethines. Its reaction with DMAD yields l-(2-methylaminophenyl)pyrazole (624), which is formed by cleavage of the initial adduct (623) (75JHC225). 

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. 

A later variation of the general method, which extends the scope to 20-ketones, involves reaction of the ketone with benzylamine to give the imine, followed by conversion to the A-acetyl derivative with acetic anhydride. Although the resulting compound also has a A -double bond, it does not react sufficiently fast with peracid, and a A -double bond can not be preserved. 

The azomethine imines exhibit the typical cycloaddition behavior expected of 1,3-dipolar species [fSJ] Numerous [3+2] cycloaddition reactions have been performed [201 204] Tetracyanoethylene adds to azomethine imines across the nitnle function instead of the C=C double bond This reaction is a rare example of this type of periselectivity [208] (equation 47)... 

In both cases, the hydride ion approaches the double bond from the sterically more accessible side of the molecule. Reduction of imines by metals and acids, electrolytically or by formic acid gives saturated secondary amines (38,255). 

It is likely that initially the open-chain adducts 353 and 354 are formed by the addition of an amino group either to the carbonyl function or to the triple bond, whereupon these intermediates close up to the azepines 355 and their bis-imine tautomers 356. In the H NMR spectra, the methylene protons of 356 are at 2.85-2.97 ppm, whereas the methyl protons are fixed at 2.20-2.27 ppm. The IR spectra show absorption bands corresponding to the aromatic ring (1600 cm ) and to the diazepine cycle C=N double bonds (1580 cm ). However, there are no bands of... 

The acetate (1) and its mosylate analog (79) have been shown to undergo cydoad-dition with the CN double bond of alkyl imines to generate substituted pyrrolidines in the presence of nickel or palladium catalyst [35]. For example, both the phenyl imine (80) and the diazene (81) gave reasonable yields of adducts (82) and (83) respectively (Scheme 2.23). 

A somewhat more complex application of this notion is represented by the CNS stimulant fencamfine (83). Diels-Alder addition of cyclopentadiene and nitrostyrene affords the norbomene derivative, 80. Catalytic hydrogenation reduces both the remaining double bond and the nitro group (81). ° Condensation with acetaldehyde gives the corresponding imine (82) a second reduction step completes the synthesis of fencamfine (83). ... 

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