Imine compounds stabilized imines

The other C=N systems included in Scheme 8.2 are more stable to aqueous hydrolysis than are the imines. For many of these compounds, the equilibrium constants for formation are high, even in aqueous solution. The additional stability can be attributed to the participation of the atom adjacent to the nitrogen in delocalized bonding. This resonance interaction tends to increase electron density at the sp carbon and reduces its reactivity toward nucleophiles. 

There are some special cases where tetrahedral intermediates are unusually stable there are three phenomena which lead to this stability enhancement. The first is an unusually reactive carbonyl (or imine) compound which is very prone to addition. An example of such a compound is trichoroacetaldehyde or chloral, for which the covalent hydrate can be isolated. A simple way to recognize such compounds is to think of the carbonyl group as a (very) stabilized carbocation, bearing an substituent. 

Additions of stabilized carbanions to imines and hydrazones, respectively, have been used to initiate domino 1,2-addition/cyclization reactions. Thus, as described by Benetti and coworkers, 2-subshtuted 3-nitropyrrolidines are accessible via a nitro-Mannich (aza-Henry)/SN-type process [165]. Enders research group established a 1,2-addition/lactamization sequence using their well-known SAMP/ RAMP-hydrazones 2-308 and lithiated o-toluamides 2-307 as substrates to afford the lactams 2-309 in excellent diastereoselectivity (Scheme 2.72) [166]. These compounds can be further transformed into valuable, almost enantiopure, dihydro-2H-isoquinolin-l-ones, as well as dihydro- and tetrahydroisoquinolines. 

The temperature at which a cycloaddition reaction of a neopentylsilene takes place (detected by the elimination of LiCl) has turned out to be dependent on the reaction partners added as substrate. This implies that an interaction between the substrate and A or B or the substrate and C occurs somewhere along the reaction pathway depicted above. For the system Cl3SiCH=CH2/LiBut/R2C=NR it was observed that the imine initiates and supports the salt elimination from the species A/B. Based on the knowledge that silenes are stabilized by external donors [1] we conclude that with carbon unsaturated compounds x-donor interactions instead of cr-donor complexes may be possible as well for the lithiated species (D) as for the silene itself (E). 

Thermolysis of 6-substituted l,5-diazabicyclo[3.1.0]hexanes 326, easily available from 325, leads to a diaziridine ring opening and to the intermediate formation of labile azomethine imines 327. These compounds can be stabilized by a proton shift to form 1-substituted 2-pyrazolines 328. However, when the thermolysis is carried out in the presence of a 1,3-dipolarophile, the corresponding products of dipolar cycloaddition can be obtained. For example, iV-arylmaleimides provide mixtures of the major trans- and minor air-products 329 and 330, respectively (Scheme 47) C1999RJO110, 2001RJ0841, 2003RJ01338, 2004RJ067>. 

Besides the allylation reactions, imines can also undergo enol silyl ether addition as with carbonyl compounds. Carbon-carbon bond formation involving the addition of resonance-stabilized nucleophiles such as enols and enolates or enol ethers to iminium salt or imine can be referred to as a Mannich reaction, and this is one of the most important classes of reactions in organic synthesis.104... 

Tris(phenylquinoxaline) compounds containing two imine nitrogens on a phenyl ring, possess high EA (2.6-2.8 eV), high mobility (10-4 cm2/(V s) at 106 V/cm), and good thermal stability. Star-shaped TPQ (91) was investigated for application as an ETM in a PPV-based... 

Compounds of the general formula 69 are prepared by cycloaddition of N-methyl- or A(-arylmaleimides with arylidene imines of AAs and in the presence of an aromatic aldehyde. Stabilized azomethine ylides are formed as intermediates, which then afford the cycloadducts. Several isomers are formed, and the influence of various metal salts and solvents was investigated (87BCJ4067 88T557). Similar transformations have been performed with A-ailyl glycine esters (91TL1359). 

UV irradiation of the naphthalen-l,4-imines 104 and 105 promotes their isomerization to 3-benzazepine derivatives 139 and 140. Although no direct evidence was obtained to confirm the formation of azaquad-ricyclanes (138) as intermediates (see Section II,F), the extra strain associated with structure 138 and the extra benzenoid stabilization of the products 139 and 140 make it understandable that the thermal rearrangement of 138 should occur faster than that of 76 or 78. Analogous photochemical transformations are those of compound 106 to trimethyl 3-benzazepin-l,3,5-tricarboxylate, and of 1,4-epoxynaphthalenes to benzoxepin derivatives. ... 

The parent compound (i), (7), is very difficult to prepare by the standard method from malonaldehyde and ethylenediamine [68JCS(B)1536], although it is one of the most stable, but can be prepared readily from imines of malonaldehyde and ethylenediamine under nonaqueous conditions (73S791). This is apparently because, despite its thermodynamic stability, it is hydrolyzed readily in aqueous solution. (Thus chromatographic separations, successful with many dihydrodiazepines, can result in progressive loss of material.) In contrast, derivatives substituted at positions 5 and 7 are hydrolyzed only very slowly, if at all, nucleophilic attack at these positions being sterically inhibited by the substituents. 

R> = Me, R = R3 = Ph, K = H, R = N=CHAr), which with ammonia in chloroform solution give novel derivatives (224) of meso-ionic l,2,4-triazol-3-imines (216). These compounds are of interest in that they belong to a new type of meso-ionic heterocycle in which the exocyclic substituent f (see Table I) is a stabilized carbanionoid residue,... 

The preparation of thiiranes is most conveniently performed in solution. However, there are also protocols reported for reaction in the gas and solid phase. By using diazo and thiocarbonyl compounds in ether as solvent, both alkyl and aryl substituted thiiranes are accessible. As indicated earlier, aryl substituents destabilize the initially formed 2,5-dihydro-1,3,4-thiadiazole ring and, in general, thiiranes are readily obtained at low temperature (13,15,35). On the other hand, alkyl substituents, especially bulky ones, enhance the stability of the initial cycloadduct, and the formation of thiiranes requires elevated temperatures (36 1,88). Some examples of sterically crowded thiiranes prepared from thioketones and a macro-cyclic diazo compound have been published by Atzmiiller and Vbgtle (106). Diphenyldiazomethane reacts with (arylsulfonyl)isothiocyanates and this is followed by spontaneous N2 elimination to give thiirane-2-imines (60) (107,108). Under similar conditions, acyl-substituted isothiocyanates afforded 2 1-adducts 61 (109) (Scheme 5.23). It seems likely that the formation of 61 involves a thiirane intermediate analogous to 60, which subsequently reacts with a second equivalent... 

In the late 1980s, accustomed thinking about the namre of nitrile imines was upturned by the discovery that these intermediates could be stabilized by the use of appropriate C and N substituents to such a degree that they could be obtained as stable isolable compounds (15,16). Some examples are shown below 16-24. Most of them are quite thermally stable and are insensitive to air and water (e.g., 16). The first such nitrile imine (16) to be prepared has a mp of 100 °C. Even example 23 with carbon-based substituents has a mp of 60 °C. It appears that the major factor in the kinetic stabihty of these compounds is the steric bulk of the C and N substiments. 

Thus in the N-silyl substituted series, 17 and 18, which rearrange thermally to the corresponding diazo compounds, the stability increases through the series R=Me, Ph, i-Pr. As discussed below, these compound undergo the usual cycloaddition and electrocyclization reactions of nitrile imines and are not simply overstabilized curiosities. The usefulness in synthesis of those with P—C bonds is probably limited since these bonds are not easily broken, but products derived from those with C—Si and C—B bonds (e.g., 21 and 22) should be capable of further... 

Two general methods are available for the assembly of the sterically stabilized species 16-24, both starting from metallic derivatives of diazo compounds (147) (16). The latter have two nucleophilic centers and can, in principle, react with electrophiles at C giving the functionalized diazo compounds (148), or at N, which leads to the nitrile imines (149). 

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