Synthesis of Nitriles from Aldehydes

This conversion is generally achieved by converting the aldehyde into oxime followed by its dehydration by a variety of reagents. One pot synthesis has also been developed , but these methods suffer from a number of drawbacks. In the microwave assisted reaction, the aldehyde is converted into oxime by reaction with hydroxylamine hydrochloride and potassium fluoride on alumina 

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Efficient One Pot Synthesis of Nitriles from Aldehydes in Solid State Using Peroxymonosulfate on Alumina (Bose and Narsaiah, 1998)... 

A new method, employing 0-(2-aminobenzoyl)hydroxylamine and BF3 Et20, has been discovered for the synthesis of nitriles from aldehydes yields are 78-94 % (Eq. 90) [147]. 

Reddy, M.B.M. and Pasha, M.A. 2010. Environment friendly protocol for the synthesis of nitriles from aldehydes. Chin. Chem. Lett. 21 1025—1028. 

Rokade BV, Prabhu JR (2012) Chemoselective Schmidt reaction mediated by triflic acid selective synthesis of nitriles from aldehydes. J Org Chem 77(12) 5364-5370 Nimnual P, Tummatorn J, Thongsornkleeb C, Ruchirawat S (2015) Utility of nitrogen extmsion of azido complexes for the synthesis of nitriles, benzoxazoles, and benzisoxazoles. J Org Chem 80(17) 8657-8667... 

Telvekar VN, Patel KN, Kundaikar HS, Chaudhari HK (2008) A novel system for the synthesis of nitriles from aldehydes using aqueous ammonia and sodium dichloroiodate. Tetrahedron Lett 49(14) 2213-2215... 

Bose DS, Narsaiah AV (1998) Efficient one pot synthesis of nitriles from aldehydes in soUd state using peroxymonosulfate on alumina. Tetrahedron Lett 39(36) 2177-2179... 

Yamazaki S, Yamazaki Y (1990) A catalytic synthesis of nitriles from aldehydes and alcohols in the presence of aqueous ammonia by oxidation of NiS04-K2S20g. Chem Lett 19 (4) 571-574... 

Dornan LM, Cao Q, Flanagan JCA, Crawford JJ, Cook MJ, Muldoon MJ (2013) Copper/TEMPO catalysed synthesis of nitriles from aldehydes or alcohols using aqueous ammonia and with air as the oxidant Chem Commun 49(54) 6030-6032... 

A microwave promoted, concerted, facile and one-pot method for the synthesis of nitriles from aldehydes via elimination of tert-butanesulfenic acid from tert-bu-tanesulfmyl protected imines has been presented by Tanuwidjaja et al. (2007). The mild reaction conditions exhibit broad functional group compatibility and generate products in good yields (69-87%). This method provides a rapid and mild procedure for the synthesis of various functionalized nitriles. 

A synthesis of nitriles from the cyanohydrins of aromatic aldehydes via the reduction of the corresponding a-halo cyanides has been proposed. As an example, benzaldehyde cyanohydrin is converted by the action of thionyl chloride to phenylchloroacetonitrile (80%). This substance is reduced with zinc in acetic acid to phenylacetonitrile (70%). ... 

Additional examples of synthetic application of periodic acid as an oxidant include the oxidative iodination of aromatic compounds [1336-1341], iodohydrin formation by treatment of alkenes with periodic acid and sodium bisulfate [1342], oxidative cleavage of protecting groups (e.g., cyclic acetals, oxathioacetals and dithioacetals) [1315, 1343], conversion of ketone and aldehyde oximes into the corresponding carbonyl compounds [1344], oxidative cleavage of tetrahydrofuran-substituted alcohols to -y-lactones in the presence of catalytic PCC [1345] and direct synthesis of nitriles from alcohols or aldehydes using HsIOe/KI in aqueous ammonia [1346],... 

Oishi T, Yamaguchi K, Mizuno N (2010) An efficient one-pot synthesis of nitriles from alcohols or aldehydes with NH3 eatalyzed by a supported ruthenium hydroxide. Top Catal 53(7) 479-486... 

By-Products. Almost all commercial manufacture of pyridine compounds involves the concomitant manufacture of various side products. Liquid- and vapor-phase synthesis of pyridines from ammonia and aldehydes or ketones produces pyridine or an alkylated pyridine as a primary product, as well as isomeric aLkylpyridines and higher substituted aLkylpyridines, along with their isomers. Furthermore, self-condensation of aldehydes and ketones can produce substituted ben2enes. Condensation of ammonia with the aldehydes can produce certain alkyl or unsaturated nitrile side products. Lasdy, self-condensation of the aldehydes and ketones, perhaps with reduction, can lead to alkanes and alkenes. 

Z)-a,f - Unsaturated nitriles. A highly selective synthesis of essentially pure (Z )-a,/ -unsaturated nitriles from aldehydes is possible by use of 1 (equation I).1... 

Structure of the Carbonyl Group 817 18-3 Nomenclature of Ketones and Aldehydes 818 18-4 Physical Properties of Ketones and Aldehydes 820 18-5 Spectroscopy of Ketones and Aldehydes 822 18-6 Industrial Importance of Ketones and Aldehydes 828 18-7 Review of Syntheses of Ketones and Aldehydes 829 18-8 Synthesis of Ketones from Carboxylic Acids 833 18-9 Synthesis of Ketones and Aldehydes from Nitriles 833... 

Hydrogenation of aromatic nitro compounds to aromatic amines Hydrogenation of aldehydes and ketortes to alcohols Hydrogenation of atomic olehnic groups Hydrogenation of unsaturatcd nitriles to unsaturated amines Hydrogenation of diolefins artd alkynes to monoolehns Hydration of ethylene oxide alkylation of aromatics with olehns oxidation of alcohols to aldehydes Oxidation of ethylene to ethylene oxide Synthesis of HCN from NH, and CH4 Oxidation of CH3OH to HCHO... 

Nitriles from aldehyde-bisulfite compounds CH(OH)S03H —CH2CN Synthesis with addition of 1 C-atom... 

It is clear that further reaction of the hydrocarbons produced in reaction (3) will produce a more complicated series of aldehydes and nitriles via reactions (1) and (2). In the presence of liquid water, a still more complicated reaction sequence becomes possible. Because of the limitations of space, I shall confine the discussion to the possible production of the components of proteins and nucleic acids. The principle pathways of interest here are the synthesis of carbohydrates from formaldehyde and the formation of amino acids, purines and pyrimidines by reactions involving aqueous solutions of HCN. [Although there have been suggestions that HCN can undergo direct polymerization in the gas phase (Matthews and Moser, 1966 Matthews et al., 1977), this reaction has never been directly observed.]... 

When mixed with alkylcopper reagents (MeCu or r-BuCu are the most common), DIBAL-H gives selective 1,4-reduction of conjugated carbonyl compounds. An example, taken from Corey s synthesis of desogestrel, is the conversion of 189 to 190 in 91 % yield, using HMPA as a solvent.220 DIBAL-H is also an effective reagent for the reduction of nitriles to aldehydes, as in the reduction of 191 to 192 in 72% yield221... 

Another variant of this HCN addition to polar C=X bonds is the Strecker synthesis of aminonitriles from ketones or aldehydes, HCN, and ammonia [Eq. (4)] [8]. A number of patents to Distler and co-workers at BASF do teach the use of aqueous media to facilitate isolation of pure products [9], and researchers at Grace [10], Stauffer [11], Mitsui [12], and Hoechst [13] have reportedly used aqueous media to control the rates of formaldehyde aminohydrocyanation to isolate intermediate addition products in good yields. The use of aqueous media has also proven advantageous when amides, rather than nitriles, are the desired products. 

Other reactions of carbohydrates include those of alcohols, carboxylic acids, and their derivatives. Alkylation of carbohydrate hydroxyl groups leads to ethers. Acylation of their hydroxyl groups produces esters. Alkylation and acylation reactions are sometimes used to protect carbohydrate hydroxyl groups from reaction while a transformation occurs elsewhere. Hydrolysis reactions are involved in converting ester and lactone derivatives of carbohydrates back to their polyhydroxy form. Enolization of aldehydes and ketones leads to epimerization and interconversion of aldoses and ketoses. Addition reactions of aldehydes and ketones are useful, too, such as the addition of ammonia derivatives in osazone formation, and of cyanide in the Kiliani-Fischer synthesis. Hydrolysis of nitriles from the Kiliani-Fischer synthesis leads to carboxylic acids. 

Sharghi, H. and Hosseini-Sarvari, M. 2002a. A direct synthesis of nitriles and amides from aldehydes using dry or wet alumina in solvent free conditions. Tetrahedron. 58(52) 10323-10328. 

Benzimidazole ring-bearing heterocyclic compounds are important in pharmacology and medicinal chemistry. The synthesis of benzimidazoles from o-phenylenediamines and carboxylic acids or nitriles needs harsh conditions. Hence, the synthesis of benzimidazoles can be accomplished with < -phenylenediamines and aldehydes. Benzimidazole derivatives were synthesized by the reaction of o-phenylenediamine with either aldehydes or nitriles in the presence of SSA as a cheap and readily available heterogeneous catalyst in refluxing ethanol (Sadeghi and Nejad, 2013) (Scheme 5.16). The protocol is beneficial in terms of short reaction time, high yield, and operational simplicity. Salehi et al. (2006) synthesized... 

Another widely used dehydration agent for the synthesis of cyanides from amides is phosphoryl chloride. For example, the amide 1430 is dehydrated with this reagent to give amino nitrile 1431, which is an auxiliary with a disymmetric tertiary amino group employed in an asymmetric nucleophilic acylation reaction with an aldehyde according to the following reaction sequence to afford chiral acetophenone 1433 [1089]. 

Hajipour, A. R., Ghayeb, Y., and Sheikhan, N. (2010). Zr(HS04)4 catalyzed one-pot Strecker synthesis of a-amino nitriles from aldehydes and ketones under solvent-liee conditions. J. Iran. 

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