Amination reactions elimination

Enamines derived from aldehydes can usually be obtained by the reaction of 2 equivalents of a secondary amine with the carbonyl compound, in the presence of anhydrous potassium carbonate, followed by pyrolytic distillation of the aminal with elimination of one of the amine groups (10,15, 30-36). Ketones are directly converted to enamines under the conditions of aminal formation. The azeotropic removal of water with excess aldehyde has also been described (32,37). 

Together with a shift of the proton from the a-carbon to the alkoxide oxygen, the tertiary amine is eliminated from the addition product to yield the unsaturated product 3. Early examples of the Baylis-Hillman reaction posed the problem of low conversions and slow reaction kinetics, which could not be improved with the use of simple tertiary amines. The search for catalytically active substances led to more properly adjusted, often highly specific compounds, with shorter reaction times." Suitable catalysts are, for example, the nucleophilic, sterically less hindered bases diazabicyclo[2.2.2]octane (DABCO) 6, quinuclidin-3-one 7 and quinuclidin-3-ol (3-QDL) 8. The latter compound can stabilize the zwitterionic intermediate through hydrogen bonding. ... 

Azoniaspiro[4.8]tridecane 129 was formed from the substituted triazacyclononane 128 (X = OMe) on standing in methanol for ten days (Scheme 15) <2000AJC791 >. It was precipitated as the tetraphenylborate salt 130 (X = BPli, ) since attempts to isolate the methoxide derivative by evaporation of the solvent led to elimination reactions yielding a mixture of triazacyclononane 131 and allene 132 in the ratio of 1 10. Re-dissolution of these allows further hydro-amination reactions to occur. Precipitation and analysis of their tetraphenylborate salts suggested the products to be 130-132 in a ratio of 1 8 1. Owing to their chemical similarities these components were not isolated. 

In order to eliminate the requirement of using at least 2 equivalents of RM (M = Li, MgBr) in their amination with the reagents 3i-o, e.g. 1 equivalent for the deprotonation of amino hydrogen and 1 equivalent for the amination reaction, A-metallated derivatives of 3i-o have been used. The lithium derivative of 31, e.g. A-lithio Af-(f-butoxycar-bonyl) 0-p-tosylhydroxylamine (A-lithio f-butyl A-tosyloxycarbamate), is also known as LiBTOC. 

Thiochrom-4-ones have also been prepared by the amine-promoted elimination of hydrogen halide from 3-haIothiochroman-4-ones,188 by the Puinmerer reaction on thiochroman-4-one S-oxides [Eq. (20)],98 from a ring expansion of activated benz[6]thiophenes [Eq. (21)],189 by the reaction of o-mercaptoaryl alkyl ketones with ethyl esters of... 

We illustrate this by two examples. Reaction of the 6-phenyl-1,2,4-triazine (407) with the enamine (406) follows orientation A since secondary orbital interactions between the n-electrons of the amino group and the 77-electrons of the phenyl ring are possible. The dihydropyridine (408) can eliminate the amine to form the cyclopenta[c]pyridine (409) since the cis orientated proton at C-3 can shift to the nitrogen to form the 1,4-dihy-dropyridine (410) from which the amine is eliminated. 

Melt poly condensation is also the most popular method for other thermotropic condensation polymers, including the polyazomethines where the reaction between aromatic aldehydes or ketones and primary amines with elimination of water leads to azomethine (Schiffs base) formation 48). 

The 2-dRL lesion and the 3 -fragment resulting from reaction (13) were identified by mass spectrometry. The bona fide intermediate (in brackets) expected to be formed upon treatment with a base such as piperidine was not observed, but the p,6-elimination product [reaction (14)] and an adduct of the amine [reaction (15)] were identified. 

Oxidative Deamination. Oxidative deamination of amphetamine occurs in the rabbit liver but not to any extent in the liver of either the dog or the rat, which tend to hydroxylate the aromatic ring. A close examination of the reaction indicates that it is probably not an attack on the nitrogen but rather on the adjacent carbon atom, giving rise to a carbinol amine, which eliminates ammonia, producing a ketone ... 

Hydroxyls can act as nucleophiles, although they are less nucleophilic than amines or thiols. Under acidic conditions, hydroxyls can be eliminated in a dehydration reaction (Fig. 79). Elimination reactions can occur as an El reaction (elimination unimolecular) or E2 reaction (elimination bimolecu-lar). The El elimination mechanism proceeds through formation of a carbo-cation intermediate as the rate-determining step with loss of water whereas the E2 mechanism is second order with the base abstraction of a proton and loss of the leaving group occurring simultaneously (120). 

A pharmaceutical intermediate was initially produced at a scale of 500 kg (product) per batch in a 2.5 m3 reactor. The reaction was the condensation of an amino-aromatic compound with an aromatic chloride to form a di-phenyl amine by elimination of hydrochloric acid. This acid was neutralized in situ by sodium carbonate, forming water, sodium chloride, and carbon dioxide. The manufacturing procedure was very simple The reactants were mixed at 80 °C, a temperature above the melting point of the reaction mass. Then the reactor was heated with steam in the jacket to a temperature of 150 °C. At this temperature, the steam valve had to be closed and the reaction left to proceed for a further 16 hours. During this time, the temperature increased to a maximum of 165 °C. Several years later, the batch size was increased to 1000 kg per batch in a 4 m3 reactor. Two years after this a further increase to 1100 kg was decided. 

The high element effects for the reactions of amines with (11) and (12) suggest multiplicity of mechanistic routes. The second-order kinetics and the very slow exchange of cis-bromo-(ll-a-D) in isopropanol fit addition-elimination (Ghersetti et al., 1965). In methanol, exch/ nub values for reaction of cyclohexylamine with cis and iraws-chloro-(ll) and cis- and Jrans-bromo-(ll) are 13, 11, 20 and 23, respectively, and 0-9, 0-6, 1 4 and 0-8 for the corresponding reactions of di-n-butylamine. While (rans-bromo-(ll) and cis-chloro-(ll) showed normal kinetics in methanol and in ethanol, the rate constants with cis-bromo- (11) and (12) decreased with time, but steady second-order behaviour could be achieved by addition of the perchlorate of the amine used. While this fits an amine-promoted elimination-addition, where the ammonium salt formed shifts the equilibrium to the left (equation 15), the slow... 

A plausible mechanism for the one-pot synthesis ofcarbazoles is shown in Scheme 5. It consists of two interlinked catalytic cycles. In the first cycle a classical Buchwald-Hartwig amination reaction occurs to generate an intermediate 5 which then enters the second cycle by oxidative addition to Pd(0). The resulting Pd(II) complex then undergoes intramolecular C-H activation to give a six-membered palladacycle which subsequently yields the carbazole by reductive elimination. 

Metal nitrene complexes were used in a number of C-H amination reactions (recent reviews [358, 359]). Copper ketiminate complexes react with azides to nitrene complexes, which were isolated [360]. (p-Ketiminate)copper(I) complex 262 (2.5 mol%) serves therefore as an efficient catalyst for the intermolecular C-H amination of alkylarenes, cycloalkanes, or benzaldehydes 260 using adamantyl azide 261 as the nitrogen source ig. 68) [361]. The corresponding adamantyl amines or amides 263 were isolated in 80-93% yield. Copper complex 262 forms initially a dinuclear bridged complex with 261. From this a copper nitrene complex is generated by elimination of nitrogen, which mediates the hydrogen abstraction from 260. 

Other types of allylic amination reactions include a variety of indirect approaches such as reduction of a,P-unsaturated imines and oximes, rearrangement of aziridines, and elimination of water from vicinal amino alcohols. However, these reactions will not be considered in this chapter [2]. 

Either the tertiary amine or the quaternary ammonium salt can be stored as a stable equivalent of the exo-methylene compound. In our first example, the Mannich base with dimethylamine is first methylated with methyl iodide and then added to the conjugate addition reaction. Elimination of trimethylamine, which escapes from the refluxing ethanol as a gas, reveals the exo-methylene ketone in which the methylene group is exo to a chain. Fast conjugate addition of the stabilized enolate of diethyl malonate produces the product. 

Two problems had to be solved for these reactions to be made usefiil. First, reductive elimination to form C N and bonds was not a well-known reaction with classical ligands such as PPh3. Second, jS-hydride elimination is very facile for primary and secondary heteroatom substrates. As with other cross-coupling reactions, the use of hindered, basic phosphines turned out to be cmcial. Amination reactions tend to give better yields, since reductive elimination is faster for more basic groups. For example, the base used in catalytic aminations is Na-O-t-Bu, but the product is the aryl amine. 

A second issue is that catalytic aminations are plagued by several notable side reactions. Most prevalent among these is jS-hydride elimination (see -Hydride Elimination) of imine from the intermediate Pd-amido complex (equation 31). This reaction also produces a Pd H species, which can then reduce the substrate to form arene, the generation of which can be considered a second side reaction. Furthermore, aryl-aryl exchange has also been noted in amination reactions, and, for the monoarylation of primary amines, by-products caused by overarylation (equation 32) to form tertiary amines pose an additional difficulty. 

Pyrrole and N-substituted pyrroles are formed by a reaction analogous to the conversion of sugars to furan aldehydes. Ammonium and substituted ammonium salts of mucic acid, H02C(CH0H)4C0jH, are cyclized and de-carboxylated by pyrolysis. The yields of pyrrole and its N-phenyl and N-methyl derivatives are about 40%. Tetrahydropyrroles (pyrrolidines) are formed from various 4-substituted amines by elimination of water, ammonia, or hydrogen halide. ... 

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