Nitriles aldehyde derivatives

Quaternary hydrazonium salts (derived from aldehydes) give nitriles when treated with OEt or DBU (p. 488, 1337) as do dimethylhydrazones RCH— NNMe2 when treated with Et2NLi and HMPA. All these are methods of converting aldehyde derivatives to nitriles. For the conversion of aldehydes directly to nitriles, without isolation of intermediates, see 16-21. 

The analytical data obtained, particularly by the PUMA mass spectrometer on board Vega 1 during the flyby, indicate the presence of a large number of linear and cyclic carbon compounds, such as olefins, alkynes, imines, nitriles, aldehydes and carboxylic acids, but also heterocyclic compounds (pyridines, pyrroles, purines and pyrimidines) and some benzene derivatives no amino acids, alcohols or saturated hydrocarbons are, however, present (Kissel and Krueger, 1987 Krueger and Kissel, 1987). 

Solvents can be classified into three categories according to their polarity namely, polar protic, dipolar aprotic and non-polar. Most of the common solvents fall under one of following chemical classes Aliphatic hydrocarbons, aromatic hydrocarbons, alcohols, phenols, ethers, aldehydes, ketones, carboxylic acids, esters, halogen-substituted hydrocarbons, amines, nitriles, nitro-derivatives, amides and sulfur-containing solvents (Marcus, 1998). In certain cases a mixture of two or more solvents would perform better than a single solvent. 

Under mildly basic conditions, methoiodides prepared from aldehyde-derived SAMP-hydrazones are converted to nitriles 28. 

Isoxazoles and their partially or fully saturated analogs have mainly been prepared, both in solution and on insoluble supports, by 1,3-dipolar cycloadditions of nitrile oxides or nitrones to alkenes or alkynes (Figure 15.10). Nitrile oxides can be generated in situ on insoluble supports by dehydration of nitroalkanes with isocyanates, or by conversion of aldehyde-derived oximes into a-chlorooximes and dehydrohalogenation of the latter. Nitrile oxides react smoothly with a wide variety of alkenes and alkynes to yield the corresponding isoxazoles. A less convergent approach to isoxazoles is the cyclocondensation of hydroxylamine with 1,3-dicarbonyl compounds or a,[3-unsatu-rated ketones. 

Undecylenyl aldehyde, which can be derived from castor oil, has also been used as CM partner of acrolein and acrylonitrile [73]. C5 (1 mol%) led to 94% isolated yield of the a,co-nitrile-aldehyde by reaction with acrylonitrile in toluene at 80°C. A twofold excess of acrylonitrile was necessary to prevent the production of... 

This chapter includes not only nuclear and extranuclear pyrazinecarboxylic acids and anhydrides, but also the related esters, acyl halides, amides, hydrazides, nitriles, aldehydes, ketones, and any of their thio analogues a few rare isothiocyanatopy-razines and pyrazinecarbonitrile oxides are also included. To avoid repetition, interconversions of these pyrazine derivatives are discussed only at the first opportunity for example, the esterification of carboxylic acids is discussed as a reaction of carboxylic acids rather than as a preparative route to carboxylic esters, simply because the section on carboxylic acids precedes that on carboxylic esters. To minimize any confusion, many cross-references have been inserted. 

Enamines. A new route to enamines involves alkylation of an a-amino nitrile (1) derived from an aldehyde to give an a-amino nitrile of type 2. When 2 is treated with potassium t-butoxide (or KOH), hydrogen cyanide is eliminated with formation of an enamine (3). The sequence is also applicable to synthesis of dienamines. 

The Vilsmeier-Haack reaction of electron-rich carbocyclic aromatic compounds (Ar—H) with chloromethyleneiminium salt (1) gives aldehyde derivatives (Ar—CHO), generally in good yield. The intermediate iminium salt (cf. salt 5 Scheme 1) can be treated with hydroxylamine to obtain nitrile derivatives (Ar—CN). Benzene and naphthalene are not sufTiciently electron rich to participate in the Vilsmeier-Haack reaction, but polycyclic hydrocarbons, such as anthracene, do react. Benzene and naphthalene derivatives that possess an electron-releasing substituent (—OMe,—SMe,—NMe2, etc.) af-... 

Reaction of carboxylic acids with sodium azide formed intermediate acid azides for peptide synthesis, and these are further cyclized to tetrazole derivatives. Acid nitriles, aldehydes, and dienones also reacted with sodium azide to form tetrazoles. Representative examples are displayed in eqs 32-34. 

Ubukata s synthesis [51] started with ammonolysis followed by Swern oxidation of ( )-55 [52] to give nitrile aldehyde 56. Wittig-Horner reaction of 56 with phosphonate 58 derived from glutarimide acetic acid 57 [27] gave 59. The nitrile was converted to amide 60, which was subjected to selenolac-tamization [53] to afford 61. Oxidation-elimination of the selenenide moiety gave 48 a diastereomeric mixture. 

Nitriles can be used in reactions other than displacement The Boc-protected aldehyde derived from alanine (known as N-Boc alinal, 1.161) was condensed with potassium cyanide to give a cyanohydrin. Hydrolysis of the cyano group to give an acid and removal of the N-Boc group gave 3-amino-2-hydroxybutanoic acid, 1.162.9 ... 

Novel regioselective one pot approach to pyrazolo[l,5-a]- and imidazo[l,2-a]-pyrimidine derivatives (219) involved their generation in situ from nitrile, aldehyde and amino heterocycles (Scheme 85)/ ... 

IV. Ammoniiun salts of carboxylic adds, aldehyde-ammonias, amides, imides, nitriles. Acyl derivatives of bases (JV-substituted amides). Hydrazines, semicarbazide, hydroxyl-amine, their salts and carbonyl derivatives. Condensation products of aldehydes with ammonia or amines. 

Ammonium Salts of Carboxylic Adds Aldehyde-ananomas Anodes Inodes Nitriles Acyl Derivatives of Bases Hydrazines, Sendcarbazide, Hydroxylandne, their salts and carbonyl derivatives Condensation Products of Aldehydes with Amntonia or Andnes... 

A variety of other methods have been employed on a case-by-case basis to effect auxiliary cleavage, and a detailed account of these methods is available. In addition to hydrolytic approaches, for aldehyde hydrazones, a number of convenient direct methods are available that allow the auxiliary to be cleaved in such a way that a functional group other than an aldehyde is generated. For instance, aldehyde-derived SAMP/RAMP hydrazones can be directly converted into the corresponding nitriles, ° amines,or dithianes, thereby enabling subsequent reactivity not immediately available from the aldehyde itself (Scheme 7.5). 

Other carbonyl compounds are within the scope of the reaction ketones give amides, and aldehydes yield nitriles and formyl derivatives of amines ... 

The imides, primaiy and secondary nitro compounds, oximes and sulphon amides of Solubility Group III are weakly acidic nitrogen compounds they cannot be titrated satisfactorily with a standard alkaU nor do they exhibit the reactions characteristic of phenols. The neutral nitrogen compounds of Solubility Group VII include tertiary nitro compounds amides (simple and substituted) derivatives of aldehydes and ketones (hydrazones, semlcarb-azones, ete.) nitriles nitroso, azo, hydrazo and other Intermediate reduction products of aromatic nitro compounds. All the above nitrogen compounds, and also the sulphonamides of Solubility Group VII, respond, with few exceptions, to the same classification reactions (reduction and hydrolysis) and hence will be considered together. 

The conversion of carboxylic acid derivatives (halides, esters and lactones, tertiary amides and lactams, nitriles) into aldehydes can be achieved with bulky aluminum hydrides (e.g. DIBAL = diisobutylaluminum hydride, lithium trialkoxyalanates). Simple addition of three equivalents of an alcohol to LiAlH, in THF solution produces those deactivated and selective reagents, e.g. lithium triisopropoxyalanate, LiAlH(OPr )j (J. Malek, 1972). 

As mentioned previously, aldehydes can be prepared by Stephen s method of reduction of nitriles by stannous chloride (37, 91). Polaro-graphic reduction of thiazolecarboxylic acids and their derivatives gives lower yields of aldehydes (58). Ozonolysis of styrylthiazoles, for example, 2-styryl-4-methylthiazole, followed by catalytic reduction gives aldehyde with 47% yield of crude product (30). 

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