Elimination reactions nitrile-forming

In the presence of a biological unit that can react as a base (such as water or a nitrogen atom from a different molecule), the hydrogen atom from the C=NH unit in 69 is transferring electrons to carbon (forming a CN unit, a nitrile), and this electron transfer process leads to an elimination reaction that forms ethylene, and Fe(II),with transfer of the OH unit to a suitable acid. The products are ethylene and cyanoformate (which then decomposes to HCN + CO2). Ascorbic acid is utilized in this transformation. This sequence is one example in which an elimination process plays a key role in a biosynthetic transformation. 

Purpose. You wiU carry out the second step in the sequence of synthetic reactions leading to an aromatic nitrile, piperonylonitrile.You wiU prepare a specific oxime derivative of the aldehyde obtained in Experiment [El].This oxime derivative is derivatized on oxygen so as to allow the oxygen to function as a good leaving group, which wUl allow an elimination reaction to form a nitrile in the final step of the synthetic sequence leading to piperonylonitrile. 

The allyl cyanoacetate 731 can be converted into an a, /3-unsaturated nitrile by the decarboxylation-elimination reaction[460], but allyl malonates cannot be converted into unsaturated esters, the protonation and allylation products being formed instead. 

A plausible mechanism for the [2+2+2] cycloaddition reactions between diynes and heterocumnlenes (or nitriles) is shown in Scheme 5.16. Initially [2+2] oxidative addition of one alkyne and the heterocnmnlene (or nitrile) forms the five-mem-bered intermediate 54 compound 55 is formed after the insertion of the second alkyne and finally the seven-membered compound 55 undergoes reductive elimination to afford the prodnct 56 and regenerate the Ni(0) catalyst. 

Elimination reactions of ( )- and (Z)-benzaldehyde Opivaloyloximes (19a) and (19b) with DBU in MeCN have been found to occur by a nitrile-forming E2 mechanism which is ca 2000-fold faster for the latter isomer in each case.15 The corresponding Hammett substituent constants, activation parameters, and primary deuterium isotope effects, suggest that the anti elimination from (19b) (for which p = 2.4 0.1, H/ D = 2.7 0.3, A/H = 12.5 0.2 kcal mol-1, and A= —31.0 0.6eu) proceeds to (20) via a more symmetrical transition state with a smaller degree of proton transfer, less charge development at the jS-carbon and greater extent of triple bond formation than for syn elimination from (19a) (for which p = 1.4 0.1, kn/kn = 7.8 0.3, AH = 8.8 0.1 kcal mol 1 and A= -23.6 0.4 eu). 

Electron-poor nitriles react with compound 87 and its derivatives to form the 5-amino-l,2,4-thiadiazole derivatives 104 <1985JOC1295>. Therefore, the formation of product 94 (see Scheme 21) may be explained alternatively by the addition of amidonitrile 93 to compound 90. The mechanism of the formation of product 104 was discussed in detail in CHEC-II(1996) <1996CHEC-II(4)691> but most probably the steps involved are (1) reaction of the electrophilic nitrile with the exocyclic nitrogen of compound 87 or its derivatives (2) loss of nitrogen similarly to the previous reactions and formation of an imine 103 (3) masked 1,3-dipolar cycloaddition/elimination reaction of the nitrile to the imine 103. Since the same nitrile is expelled in the elimination step, only 1 equiv of reagent is needed (Scheme 24). 

The reaction sequence of most interest in this route is the conversion of 4 into 3 (Scheme 15.4). Presumably, the NaOCl that is present in the reaction mixture chlorinates the deprotonated oxime nitrogen to create an iV-chloro-nitrone 9 which then eliminates HC1 to generate the alkenyl nitrile oxide 10. The latter then undergoes the anticipated 1,3-dipolar cycloaddition reaction to form 3. 

Palomo75 report that various aromatic aldehydes can be converted to nitriles in 94-97% yield by refluxing the aromatic aldehyde, hydroxylamine hydrochloride, and magnesium sulfate in toluene or xylene, with p-toluencsulfonic acid as catalyst for 1.5 to 3 hr. The microwave-assisted process may prove better for aliphatic aldehydes and may be made even more attractive if the above process conditions could be refined to reduce or eliminate NMP—for instance, if both aldehyde and nitrile form a homogeneous liquid at the reaction temperature. 

Benzonitrile oxide (C in Figure 15.44) is an isolable 1,3-dipole. It can be generated from benzaldoxime and anNaOH/Cl2 solution. Under these reaction conditions the oxime/nitroso anion (A B) is initially formed and chlorine disproportionates into Cl—O and chloride. An SN reaction of the negatively charged C atom of the anion A B at the Cl atom of Cl— O or of Cl—O—H affords the oc-chlorinated nitroso compound E, which tautomerizes to the hydroxamic acid chloride D. From that species, the nitrile oxide C is generated via a base mediated 1,3-elimination. Isoxazoles are formed in the reactions of C with alkynes (Figure 15.44), while isoxazolines would be formed in its reactions with alkenes. 

Similar to the benzynezirconocene, cyclohexyne, cyclopen-tyne, alkyne, alkene, cycloaUcene zirconocenes, and related species insert various substrates such as alkynes, alkenes, aldehydes, ketones, nitriles or phosphaalkynes. They lead in general five-membered zirconacycles, which can be converted by transmetalation or exchange reactions into fused-ring aromatic or heterocyclic compounds. The extension of this chemistry to heterobenzyne complexes can be realized, for instance, in phosphinine compounds. Consequently, under mild conditions, ) -phosphabenzyne-zirconocene complexes are formed and can be isolated either as PMes adducts or as dimers when the elimination reaction is carried out without added phosphane (Scheme 28). 

Rearrangement-cyclization. 6-Oximino nitriles form 2-acetamidopyridines. n treatment with AC2O-ACCI under reflux. The reaction proceeds from rearrangement of iV-acetoxyenamines to C-acetoxy imines, which undergo elimination and csclization. 

Naked cyanide ion. Alkyl halides are converted into nitriles by potassium cyanide in the presence of a catalytic amount of 18-crown-6. Acetonitrile (or benzene) is used as solvent, and the two-phase system is stirred vigorously at 25-83°. Little or no reaction occurs in the absence of the crown ether, an indication that the ether is functioning also as a phase-transfer catalyst. Primary halides are also converted quantitatively into nitriles chlorides react much faster than bromides. A few percent of elimination products are formed in the reaction of secondary halides. Cyclohexyl halides give only cyclohexene by elimination. o-Dichlorobenzene fails to react. Methacrylonitrile undergoes hydrocyanation to 1,2-dicyanopropane (92% yield). 

The thermal elimination of alkyl halides to form nitriles is perhaps the best known reaction of imidoyl chlorides. J. v. Braun investigated this reaction in detail over a period of 40 years, and he developed a host of useful new synthetic procedures for the synthesis of compounds, which are otherwise more difficult to obtain. Unfortunately, most of his work has been written up in detailed form in Chemische Berichte and it requires some effort to retrieve this information. However, he wrote one review article in 1934 which is most informative. The elimination of alkyl halides on heating of imidoyl chlorides was recognized by Wallach in 1877 and v. Pechmann and Ley and Holzweissig reported examples of this reaction prior to the work of J. v. Braun. The elimination reaction, in its most general terms, can be described by the following sequences ... 

A domino sequence comprising a cycloaddition and subsequent cycloreversion step can often find a more general application in organic synthesis, especially in the formation of aromatic compounds such as furans or pyrroles. Oxazole moieties as electron-deficient dienes often serve as the crucial reactive centers which cycloadd to a triple bond and eliminate a nitrile upon cycloreversion. If the first step is intramolecular, the impelling enthalpy preserved in the stability of the formed CN function is additionally accompanied by a positive entropy when the nitrile, sometimes volatile, leaves the substrate. In an older example from 1984 [10], Jacobi and coworkers devised a scheme for the preparation of a highly substituted furan on their synthetic way to paniculide A. An intramolecular Diels-Alder reaction was followed by the critical extrusion of volatile acetonitrile, furnishing the bicycle 8 in 94% yield (Scheme 6.2). 

Nitrile-forming eliminations from 2,4,6-trinitrobenzaldehyde 0-oxime derivatives promoted by amines in MeCN have been studied kinetically. The reactions are second-order and exhibit substantial Hammett p and Brpnsted ft values. The second-order rate constant for elimination from ( )-2,4,6-trinitrobenzaldehyde 0-pivaloyloxime promoted by /-Pr2NH in MeCN falls on a single line in the Hammett plot for different j0-aryl substituents, which have been shown to react by the E2 mechanism. The change of the /3-aryl group from phenyl to thienyl to furyl shifted the reaction mechanism from E2 to ElcE) f ... 

Nitrido complexes have also been formed by metathesis and atom transfer processes. The reaction of dinitrogen with a molybdenum(III) species forms a molybdenum-nitrido complex, as shown in Equation 13.103. and described in more detail in the section of Chapter 5 on dinitrogen complexes. In a metathesis process involving related complexes, the reaction of a metal-alkylid)me complex with a nitrile extrudes an alkyne to form a metal nitride fliat adopts a dimeric structure (Equation 13.104). - Related nitrido complexes have been formed from an azabicydic compoimd that eliminates anthracene after forming the M-N bond (Equation 13.105). ... 

The preparation of this oxime is the second step in this sequence to obtain the aromatic nitrile target molecule. In Experiment [E2] you are going to convert the aromatic aldehyde formed in Experiment [El] into an 0-phenylated oxime, which on treatment with base in Experiment [E3] yields the desired nitrile via an elimination reaction. Oxime formation is also involved in the well-known Beckmann rearrangement (see Experiment [6adv])/ which is used for the synthesis of amides. 

Esters are most commonly prepared by the reaction of a carboxyHc acid and an alcohol with the elimination of water. Esters are also formed by a number of other reactions utilizing acid anhydrides, acid chlorides, amides, nitriles, unsaturated hydrocarbons, ethers, aldehydes, ketones, alcohols, and esters (via ester interchange). Detailed reviews of esterification are given in References 1—9. 

The use of the triphenylphosphine-carbon tetrachloride adduct for dehydration reactions appears to be a very simple way of synthesizing nitriles from amides, carbodi-imides from ureas, and isocyanides from monosubstituted formamides. All of these reactions involve the simultaneous addition of triphenylphosphine, carbon tetrachloride, and tri-ethylamine to the compound to be dehydrated. The elimination of the elements of water is stepwise. An adduct, e.g. (46), is first formed, chloroform being eliminated, which decomposes to produce hydrogen chloride and the dehydrated product. 

It is believed that SCR by hydrocarbons is an important way for elimination of nitrogen oxide emissions from diesel and lean-burn engines. Gerlach etal. [115] studied by infrared in batch condition the mechanism of the reaction between nitrogen dioxide and propene over acidic mordenites. The aim of their work was to elucidate the relevance of adsorbed N-containing species for the F>cNOx reaction to propose a mechanism. Infrared experiments showed that nitrosonium ions (NO+) are formed upon reaction between NO, NOz and the Brpnsted acid sites of H—MOR and that this species is highly reactive towards propene, forming propenal oxime at 120°C. At temperatures above 170°C, the propenal oxime is dehydrated to acrylonitrile. A mechanism is proposed to explain the acrylonitrile formation. The nitrile can further be hydrolysed to yield... 

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