Aldehydes and nitriles

Amino Acids. The formation of A/-halo-a-amino acids involves halogenation of the acid anion (13). /V-Cb1oro-CX-amino acids decompose to aldehydes and nitriles, the selectivity depending on pH and stoichiometry (110). For example, AJ-chloroalanine decomposes in the 6.5—10 pH range. 

The Fiesselmann reaction has been extensively used with p-halovinyl esters, ketones,aldehydes and nitriles as reaction partners for thioglycolic acid and its derivatives. This reaction with P-halovinyl aldehydes has been extensively explored as a result of the availability of P-chloro-a,P-unsaturated aldehydes via the Vilsmeier... 

N-Bromoamino acids form within seconds after mixing aqueous bromine and the amino acid in dilute aqueous solution (ref. 6), but are not stable end products of the reaction. Thus, Friedman and Morgulis (ref. 7) found that the oxidation of amino acids by hypobromite gives aldehydes and nitriles with one carbon atom less than the original amino acid, ammonia and CO2 (Scheme 1). The proportions of aldehyde and nitrile depend on the basicity of the medium, aldehyde formation being favoured by more basic conditions. 

Due to the ability of phosphorus and boron atoms to change their coordination reversibly, they can undergo reactions with bipolar reagents such as aldehydes and nitriles. 

Reduction of carboxylic acids and esters, aldehydes, and nitriles, and the hydro-boration of alkenes with diborane in non-ethereal solvents is highly effective (Table 11.8), but reduction of nitro groups or cleavage of arena-halogen bonds does not occur [1]. However, in spite of the potential advantages, very little use appears to have been made of the procedure. 

E. Dufour, A. C. Storer, R. Menard, Peptide Aldehydes and Nitriles as Transition State Analog Inhibitors of Cysteine Proteases , Biochemistry 1995, 34, 9136 - 9143. 

TL627>. Other metal-catalyzed reactions include the CdC -mediated cyclization of enamines in the presence of a cyano substituent (Scheme 98) <1995JOC5243>. Zinc and copper (i) salts can be used in place of the cadmium however, organocadmium promoters allow room temperature cyclization. A two-step process involving tungsten alkynols, aldehydes, and nitriles in the presence of a Lewis acid yields pyridines (Scheme 99) <1998JA4520>. 

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. 

On the other hand, our own group and Jochims and coworkers in Germany found recently and independently another pathway for formation of the A -acyliminium ions from aldehydes and nitriles in which the order of activation of the reagents differs from that in the Ritter reaction. The method involves an initial electrophilic activation of the... 

Simple distillation cannot separate aromatics from noD -aromatic, because the relative volatilities are very low, and many azeotropes are formed. Azeotropic distillation is based on the formation of an azeotrope betu een the non-aromatic hydrocarbons and a low boiling polar solveat It is select among the hrst terms of the series of alcohols, ketones, aldehydes and nitriles, and is employed pure or mixed with water. If the solvent forms a hetero-azeotrope, its recovery is accordbgly facilitated. The )aeld is not limited in principle. The impurity content of the feedstock and the composition of the azeotrope determine the amount of solvent required. Cuts rich in aromatics can be treated in this way fairly economically. However, any variation in the type of impurity to be removed, and consequently in the composition of the azeotrope, may lead to less perfect purification. Furthermore, this method can be applied only to a narrow cut which contains... 

Aldehydes are one of the most impotent synthons in organic chemistry. Many methods of preparation of formyl carboranes have been discussed previously (E. I. Rosemund method,14 Sonn-Miller reaction,14 reaction of dodecaborane with diacylal of propargyl aldehyde,14 Swem Oxidation15). Since oxazolines are rather good reagents for the preparation of aldehydes and nitriles, we developed a method of preparation of carboranyl oxazolines (Scheme 9). 

Further applications can be mentioned briefly. SAMP was used in the resolution of 4-demethoxy-7-deoxydaunomycinone/ in ee determinations (Scheme 1), as a chelate for tetracarbonylmolybdenum complexes/ in intramolecular Heck reactions, as polysilylated hydrazine, in the enantioselective synthesis of isoquinuclidines, and in the conversion of hydrazones to aldehydes and nitriles. The structure of a chiral lithium SAMP hydrazone azaenolate has been determined. In cases where SAMP did not lead to satisfactory inductions, a modified auxiliary, (S)-l-amino-2-dimethylmethoxymethylpyrrolidine (SADP), enhanced the stereochemical control. 

This method provides easy access to 4-alkylbenzoyl chlorides, which are useful intermediates in the preparation of diaryl esters that have mesomorphic properties. Benzoyl chlorides substituted in the 4-position also serve as starting materials for the preparation of aromatic aldehydes" and nitriles, whereas the acids, derivable quantitatively from the acid chlorides, are good precursors via the Schmidt reaction to 4-substituted anilines. 

Argentic oxide, AgO, which is prepared by the electrolysis of silver nitrate in nitric acid [379], converts aromatic methyl homologues into aldehydes [380], primary alcohols into aldehydes [380] or acids [381], aldehydes into acids [382], primary amines into aldehydes and nitriles [381], and phosphines into phosphine oxides [38i]. 

We can thus conclude that the amino acids do not represent a negligible part of the overall residual (10—30%). The amino acid release by filter in drinking-water may present a danger of bacterial proliferation in the drinking-water distribution system, since the carbon source is easily biodegradable. Such a hazard can be minimized by a superchlorination at the end of the treatment. However, previous [12, 13 ] and more recent [14, 15] research has shown that the action of sodium hypochlorite on ctamino acids rapidly leads to the formation of aldehydes and nitriles. Therefore, postchlorination only changes the problem to a more complex one. 

If these molecules are not toxic they are nevertheless unwanted since amino acids are easily assimilated, and they may be precursors of bacterial regrowth. Also the final chlorination of these molecules leads to the formation of aldehydes and nitriles [ 14, 25 ], which are probably more toxic than the original amino acid. 

As a general mle, unless an anion-stabilizing group, such as phenyl, or a heteroatom such as sulfur is present, the alkylsilane is not readily deprotonated. The a-halosilane can be deprotonated but, unlike the readily available chloromethyltrimethylsilane, there are few general methods to this approach. Al-kyllithium reagents add to vinylsilanes ( ) to produce the carbanion (287). Silyl derivatives with heteroatoms, such as sulfur, selenium, silicon or tin, in the a-position (288) may be transmetallated (Scheme 41). Besides the difficulty in synthesizing the anion, alkene formation lacks specificity for simple di- and tri-alkyl-substituted alkenes. As a result, the Peterson reaction of an a-silyl carbanion with a carbonyl has found the greatest utility in the synthesis of methylene derivatives, (as discussed in Section 3.1.3), heterosubstituted alkenes and a,p-unsaturated esters, aldehydes and nitriles. 

Since the precursor acids, aldehydes and nitriles (e.g. 39 and 44) are stable and readily available, this is a convenient route to 2-aminofuran derivatives. Although it is not a direct route to the primary amines, it is a useful method for making carbamate (42) or amide (43) derivatives, which are usually stable and can be further modified. This method is particularly useful for preparing N-stabilised derivatives when the furan ring does not carry an electron-withdrawing stabilising group (Table 6). 

As bifunctional electrophiles, 1,3-dicarbonyl compounds are often used. In these cases, A-aminoazoles are built up by the pyridazine (as in 357) or by the 1,2,3-triazine (as in 358) cycle. The use of other bifunctional electrophiles allows the types of annelated rings to vary. The bifunctional electrophile can be replace by two monofunctional ones, for instance, by aldehyde and nitrile, which are sequentially introduced into the reaction. 

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.]... 

The iV-acyl-imine (426) cyclo-adds to aromatic aldehydes and nitriles to give 1,3,5-dioxazines and 1,3,5-oxadiazines, respectively. Treatment of divinyl sulphide with thiourea affords the 1,3,5-dithiazine (427). ... 

Figure 5.12. Pathways for formation of aldehydes and nitriles from amino acids and...

A secondary amide is obtained by selective oxidation of a tertiary carbon center in adamantane with NaI04 in the presence of iron(III) perchlorate in acetonitrile (eq 18). Dimethylhydra-zones undergo periodate induced hydrolysis, at pH 7, to give carbonyl compounds in high yields (eq 19). However, these conditions are unsuitable for the hydrolysis of dimethylhydrazones derived from aromatic or a,unsaturated aldehydes because mixtures of aldehydes and nitriles are formed. 

Variations of this reaction have been applied over the years, typically involving the condensation of 2-aminothiophenols with substituted carboxylic acids, acyl chlorides, aldehydes, and nitriles. Initially, the reaction involves the formation of an imine that cyclizes spontaneously and then oxidation to form benzothiazole. An application of this chemistry has been showcased in the synthesis of 2-(4-aminophenyl)benzothiazoles and the evaluation of their in vitro and in vivo activities against breast cancer cell lines, with compound a exhibiting the most potent growth inhibition. Unfortunately, there are limitations due to the difficulties met during the syntheses of readily oxidizable o-aminothiophenol-bearing substituents. 

---