Amines to imines

Aromatization of indolines is important in completing synthetic sequences in which the directive effects of the indoline ring have been used to achieve selective carbocyclic substitution[l]. Several methods for aromatization have been developed and some of these are illustrated in Table 15.2. A range of reagents is represented. One type of procedure represents use of oxidants which are known to convert amines to imines. Aromatization then provides the indole. Such reagents must not subsequently oxidize the indole. Mereuric acetate (Entry 1) is known to oxidize other types of amines and presumably reacts by an oxidative deprotonation ot- to the complexed nitrogen. 

The perruthenate procedure (Entry 2) is also based on a general amine to imine oxidation. The iodosobenzene method (Entry 3) is an application of a... 

Recently Turner and coworkers have sought to extend the deracemization method beyond a-amino acids to encompass chiral amines. Chiral amines are increasingly important building blocks for pharmaceutical compounds that are either in clinical development or currently licensed for use as drugs (Figure 5.7). At the outset of this work, it was known that type II monoamine oxidases were able to catalyze the oxidation of simple amines to imines in an analogous fashion to amino acid oxidases. However, monoamine oxidases generally possess narrow substrate specificity and moreover have been only documented to catalyze the oxidation of simple, nonchiral... 

Oxidative dehydrogenations of many macrocyclic ligand complexes have now been documented. Typically, these reactions involve conversion of coordinated secondary amines to imine groups. 

Oxidation of amines to imines.1 This Swern reagent effects oxidation of ben-zylamines to the corresponding Schiff bases in 40-60% yield. It also oxidizes in-doline to indole in 88% yield. 

The electrochemical oxidation of amines to imines and nitriles typically utilize a chemical mediator. The use of both Al-oxyl radicals [12, 13] and halogens has been reported for this process [14]. For example, the conversion of benzyl amine (14a) into nitrile (15a) and aldehyde (16a) has been accomplished using the M-oxyl radical of a decahydroquinoline ring skeleton as the mediator (Scheme 5). The use of acetonitrile as the solvent for the reaction generated the nitrile product. The addition of water to the reaction stopped this process by hydrolyzing the imine generated. A high yield of the aldehyde was obtained. In the case of a secondary amine, the aqueous... 

Laterally lithiated tertiary amides are more prone to self-condensation than the anions of secondary amides, so they are best lithiated at low temperature (—78 °C). N,N-Dimethyl, diethyl (495) and diisopropyl amides have all been laterally lithiated with aUcyllithiums or LDA, but, as discussed in Section I.B.l.a, these functional groups are resistant to manipulation other than by intramolecular attack" . Clark has used the addition of a laterally lithiated tertiary amide 496 to an imine to generate an amino-amide 497 product whose cyclization to lactams such as 498 is a useful (if rather low-yielding) way of building up isoquinoline portions of alkaloid structures (Scheme 194) ". The addition of laterally lithiated amines to imines needs careful control as it may be reversible at higher temperatures. ... 

Abstract This chapter principally concerns oxidations of organic substrates containing N, O, S, P, As and Sb. Oxidations of amines are covered first, including primary amines to nitriles or amides secondary amines to imines or other products tertiary amines to N-oxides or other prodncts (Section 5.1) and the oxidation of amides (5.2). Oxidation of ethers to esters or lactones follows (5.3), then of sulfides to sulfoxides or sulfones (5.4) and of phosphines, arsine and stibines to their oxides (5.5). A final section (5.6) concerns such miscellaneous oxidations not covered by other sections in the book. 

Hydroperoxides and peroxides oxidize primary and secondary aliphatic amines to imines. Thus f-butyl hydroperoxide oxidizes 4-methyl-2-pentyl-amine to 2-(4-methylpentylidene)-4-methyl-2-pentylamine in 66% yield [29]. Di-r-butyl peroxide reacts in a similar manner [29]. However, this reaction is... 

Primary amines at a primary carbon can be dehydrogenated to nitriles. The reaction has been carried out with a variety of reagents, among others, IF5,"9 lead tetraacetate, 20 nickel peroxide,121 NaOCl in micelles,122 S g-NiSO, 2-1 and CuCl-02-pyridine.124 Several methods have been reported for the dehydrogenation of secondary amines to imines.125 Among them126 are treatment with(l) iodosylbenzene PhIO alone or in the presence of a ruthenium complex, 27 (2) Me2SO and oxalyl chloride, 2" and (3) f-BuOOH and a rhenium catalyst. 29... 

The functions of flavoprotein enzymes are numerous and diversified.151-1533 A few of them are shown in Table 15-2 and are classified there as follows (A) oxidation of hemiacetals to lactones, (B) oxidation of alcohols to aldehydes or ketones, (C) oxidation of amines to imines, (D) oxidation of carbonyl compounds or carboxylic acids to a,(3-unsaturated compounds,... 

Oxidation of amines to imines.1 In the presence of this ruthenium complex secondary amines are oxidized to imines in >70% yield. This reaction is particularly useful for preparation of 1-azadienes. 

Oxidation of amines.1 The radical effects oxidation of primary or secondary amines to imines at 25° (4-8 hours). The products are generally isolated as the dinitrophenylhydrazones of the corresponding carbonyl compounds. 

The synthetic routes may often involve template directed condensations, a widely used reaction being the (carbonyl + amine) to imine condensation that efficiently leads to a variety of Schiff-base macrocycles [2.58-2.60, A.7, A.14], macrobicyclic cryptands [2.61-2.63] and lacunar cyclidene ligands [2.60, 2.64]. 

Aryl-A3-iodane oxidation of amines to imines also involves a combination of ligand exchange and successive reductive -elimination. Oxidation of pyrrolidine with iodosylbenzene 18 affords quantitatively an equilibrium mixture of 1-pyrroline and its trimer [72]. When oxidation of piperidine with 18 (2 equiv) was carried out in water, 2-piperidone was produced [73]. In the latter reaction, a sequence of ligand exchange and reductive -elimination was repeated two times [Eq. (38)]. 

Likewise, A-(l-propylidene)-l-propanamine is obtained in liquid phase from 1-propanamine on a Cu-containing MFI zeolite, where the zeolite acidic sites selectively converts 1-propanamine to dipropanamine and the dispersed Cu metal dehydrogenates the amine to imine.[22]... 

Fig. 21 Oxidation of amines to imines using low-valent ruthenium...

It is worthwhile to comment on the catalytic species. As opposed to oxometal species, which convert amines to imines, hydroperoxymetal complexes (MOOH) convert amines to nitrones. Thus the oxidation of amines is a convenient way of distinguishing the active species. The reactivity of oxometal versus peroxometal species is illustrated in Fig. 22. In practice, tungsten is the catalyst of choice to convert amines to nitrones [130]. 

Papaverine.—The biosynthesis of the simple benzylisoquinoline papaverine (89) is known to proceed via nor-reticuline (48) and tetrahydropapaverine (88).71 Dehydrogenation of the latter affords papaverine, and examination of the stereochemistry of the processes involved has led to the conclusion72 that loss of the proton at C-3 [in nor-reticuline (48)] is stereospecific (loss of the pro-S hydrogen atom) but removal of the C-4 proton is essentially non-stereospecific. These observations are perhaps best explained if enzyme-catalysed oxidation of (88) occurs to give (90), subsequent non-stereospecific imine-enamine isomerization occurring without enzyme participation to give (91). A further amine to imine oxidation then occurs to give papaverine (89).72... 

The oxidation of secondary amines to imines can be carried out by hydrogen transfer reaction under mild conditions using a catalytic amount of 9/2,6-dimethoxy benzo-quinone/Mn02 (Eq. 3.30) [65]. 

Secondary amines can be converted into the corresponding imines, in a highly efficient single step, upon treatment with 2 equiv. of t-BuOOH in benzene in the presence of RuCl2(PPh3)3 catalyst at room temperature [134]. This is the first catalytic oxidative transformation of secondary amines to imines, which are hardly accessible by conventional methods. A 4A molecular sieve is needed to prevent the hydrolysis of product imines in some cases. The oxidations of tetrahydroisoquinoline 61 and allylamine 63 gave the corresponding cyclic imine 62 and azadiene 64 in 98% and 80% yields, respectively (Eqs. 3.75 and 3.76). 

Mercuric acetate, HgfOCOCHjjj (mp 179-182 °C), is used for dehydrogenations, resulting in the introduction of double bonds into the a positions with respect to conjugated systems [399, 400], and for the dehydrogenation of amines to imines [401, 402]. The reagent can also demethylate tertiary amines to secondary amines [403] and introduce acetoxyl groups into the a positions with respect to double bonds [404]. 

Dehydrogenation of Primary Amines to Imines and Aldehydes or Ketones... 

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