Imines as intermediates

The photochemistry of certain A-substituted heterocycles has also been studied. As part of a continuing investigation of the photolysis of A-nitroso compounds in solution, the conversion of A-nitroso-3-azabicyclo[3.2.2]nonane (65) into the oxime (66) by photolysis in the presence of acid was reported.58 N-Nitrosopyrrolidine is similarly transformed. The mechanism of this reaction is said58 to involve elimination of NOH with the formation of an imine as intermediate, and, in fact, in the photolysis of 2-ethyl-A-nitrosopiperidine (67), the tetrahydropyridine (68) is the major product. This mechanism certainly does not operate in the photolysis of iV-nitroso-2-azacyclo-octanone, which can be rationalized on the basis of an intramolecular hydrogen transfer [Eq. (16)].59 Acyclic iV-nitrosoamides behave in a similar fashion to IV-nitrosoamines.60... 

Aldehyde (166) reacted with excess hydrazine hydrochloride to afford a pyrazoline in 63% yield a mixture of pyrazoline and pyrazolidine was obtained under an inert atmosphere.83 This reaction presumably involves the hydrazone and protonated azomethine imine as intermediates. Using (166) in excess afforded a bisintramolecular adduct in 87% yield. 

Another unusual three-component coupling reaction involving an imine as intermediate has been developed by Ishii who has shown that a C-H bond adjacent to the nitrogen atom of an imine can be activated by an iridium complex. Carbo-metallation reactions of acetylenic compounds may then be achieved, which lead to unsaturated imines 155 (Scheme 8.67) [122]. 

Now the compoimd will dissolve in water and release dapsone inside the patient. The details of this sort of chemistry will come in Chapter 14 when you will meet imines as intermediates. But at this stage we just want you to appreciate that even the relatively simple chemistry in this chapter is useful in synthesis, in commerce, and in medicine. 

Pyridoxal is the reagent in other reactions of amino acids, all involving the imine as intermediate. The simplest is the racemization of amino acids by loss of a proton and its replacement on the other face of the enamine. The enamine, in the middle of the diagram below, can be reprotonated on either face of the prochiral imine (shown in green). Protonation on the bottom face would take us back to the natural amino acid from which the enamine was made in the first place. Protonation on the top face leads to the unnatural amino acid after hydrolysis of the imine (really transfer of pyridoxal to a lysine residue of the enzyme). 

Other bis azo compounds give y-triazole JV-imines as intermediates. Thus, photolysis of sydnones (58) 94-97 and of 2,5-disubstituted tetrazoles98-99 gives w-triazoles (62). These reactions probably involve the primary formation of nitrilimines (60) which dimerize to the bis azoethylene derivatives (61) which in turn cyclize to form the v-triazole IV-imines. These, under the reaction conditions, cleave at the exocyclic N-N bond (see Section IV,F). 

Analysis of the kinetics of this catalysis points to the protonated imine as the key intermediate. 

Halogenated and halogenoalkyl substituted imines react with diazo alkanes under very mild conditions and preferentially yield aziridines [5, 146 147] Diazonium betaines have been considered as intermediates of these reactions [148,... 

Formation of C—Nu The second mode of nucleophilic addition, which often occurs with amine nucleophiles, involves elimination of oxygen and formation of a C=Nu bond. For example, aldehydes and ketones react with primary amines, RNH2, to form imines, R2C=NR. These reactions proceed through exactly the same kind of tetrahedral intermediate as that formed during hydride reduction and Grignard reaction, but the initially formed alkoxide ion is not isolated. Instead, it is protonated and then loses water to form an imine, as shown in Figure 3. 

Mechanishc studies indicated the possibihty of alkynylmercury chlorides as intermediates. They would react with amines to give 2-aminovinyhnercury chlorides which could be protonated to give enamines (or imines in the case of primary amines) (Scheme 4-13) [260]. 

Reaction of the enatiopure aldehyde 2-800, obtained from the corresponding imine by enantioselective hydrogenation, with Meldrum s acid (2-801) and the enol ether 2-802a (E/Z= 1 1) in the presence of a catalytic amount of ethylene diammonium diacetate for 4h gave 2-805 in 90 % yield with a 1,3 induction of >24 1. As intermediates, the Knoevenagel product 2-803 and the primarily produced cycloadduct 2-804 can be supposed the latter loses C02 and acetone by reaction with water formed during the condensation step (Scheme 2.178). 

On heating, dihydrooxazines (548) undergo the known [4 +2]-cycloreversion to give the previously unknown conjugated en-imines CH2=C(C02Me)CH=N—E as intermediates. The latter can be trapped in a Diels—Alder reaction at the terminal or internal electron-rich double bond. 

It is known that 1//-1,2,3-triazoles can exist in equilibrium with diazo-imines. In the conversion of 1 into 2 as intermediate the diazo-imine 3 can... 

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. ... 

These reactions have been used in the synthesis of aikaioids such as corydalic acid methyi ester 502 (Scheme i95). Isoiated from Corydalis incisa, 502 is derived from a proposed biosynthetic intermediate in the route to the tetrahydroprotoberberine aikaioids. The 1,2,3,4-tetrasubstituted ring of 502 demands control by an ortholithiation strategy, and the synthetic route proposed by Clark and Jahangir employs a lateral lithiation of 503 and addition to an imine as the key disconnection at the centre of the molecule. 

In 2003, we reported a multicomponent approach toward highly substituted 2H-2-imidazolines (65) [157]. This 3CR is based on the reactivity of isocyano esters (1) toward imines as was studied in detail by Schollkopf in the 1970s [76]. In our reaction, an amine and an aldehyde were stirred for 2 h in the presence of a drying agent (preformation of imine). Subsequent addition of the a-acidic isocyanide 64 resulted in the formation of the corresponding 2//-2-imidazolines (65) after 18 h in moderate to excellent yield. The mechanism for this MCR probably involves a Mannich-type addition of a-deprotonated isocyanide to (protonated) imine (66) followed by a ring closure and a 1,2-proton shift of intermediate 68 (Fig. 21). However, a concerted cycloaddition of 66 and deprotonated 64 to produce 65 cannot be excluded. 

---