Heterocyclic aldehydes, oxidation

The reaction of alkynyllithium compounds with alkoxycarbene tungsten complexes leads to anionic propargyl tungsten complexes (Figure 2.33 see also Figure 3.9). These intermediates are stable at low temperatures and react upon Lewis acid catalysis with aldehydes or A -sulfonyl imines to yield five-membered heterocycles [280]. Oxidative methoxycarbonylation [375] of the intermediate vinyl tungsten complex, followed by elimination of methanol leads to pyrroles or furanes (Figure 2.33 Entry 6, Table 2.22). 

Mechanisms involving glycol bond fission have been proposed for the oxidation of vicinal diols, and hydride transfer for other diols in the oxidation of diols by bromine in acid solution.The kinetics of oxidation of some five-ring heterocyclic aldehydes by acidic bromate have been studied. The reaction of phenothiazin-5-ium 3-amino-7-dimethylamino-2-methyl chloride (toluidine blue) with acidic bromate has been studied. Kinetic studies revealed an initial induction period before the rapid consumption of substrate and this is accounted for by a mechanism in which bromide ion is converted into the active bromate and hyperbromous acid during induction and the substrate is converted into the demethylated sulfoxide. 

An inorganic photoconductor such as zinc oxide can be optically sensitized by treating it with a ligand that will form a colored zinc complex. The resulting material then responds to light of the wavelength where the complex absorbs. Suitable ligands are prepared by the condensation of heterocyclic hydrazines and heterocyclic aldehydes.235 Two examples of the more than 50 disclosed in the patent literature are (114) and (115). 

In 1997, the first truly catalytic enantioselective Mannich reactions of imines with silicon enolates using a novel zirconium catalyst was reported [9, 10]. To solve the above problems, various metal salts were first screened in achiral reactions of imines with silylated nucleophiles, and then, a chiral Lewis acid based on Zr(IV) was designed. On the other hand, as for the problem of the conformation of the imine-Lewis acid complex, utilization of a bidentate chelation was planned imines prepared from 2-aminophenol were used [(Eq. (1)]. This moiety was readily removed after reactions under oxidative conditions. Imines derived from heterocyclic aldehydes worked well in this reaction, and good to high yields and enantiomeric excesses were attained. As for aliphatic aldehydes, similarly high levels of enantiomeric excesses were also obtained by using the imines prepared from the aldehydes and 2-amino-3-methylphenol. The present Mannich reactions were applied to the synthesis of chiral (3-amino alcohols from a-alkoxy enolates and imines [11], and anti-cc-methyl-p-amino acid derivatives from propionate enolates and imines [12] via diastereo- and enantioselective processes [(Eq. (2)]. Moreover, this catalyst system can be utilized in Mannich reactions using hydrazone derivatives [13] [(Eq. (3)] as well as the aza-Diels-Alder reaction [14-16], Strecker reaction [17-19], allylation of imines [20], etc. 

Hydrolysis Oxidation Photolysis Esters, lactones, amides, lactams, oximes, imides, and malonic ureas Amines, sulfides, disulfides, sulfoxides, phenol anions, thiols, nitriles, and catechols Aromatic hydrocarbons, aromatic heterocyclics, aldehydes, and ketones... 

Halides are extremely versatile intermediates. One of their more valuable and interesting transformations is dieir oxidation to carbonyl compounds, dius providing straightforward routes to relatively inaccessible compounds such as 1,2-diketones and heterocyclic aldehyde. As will be seen below, there are many, often complementary, syndietic methods for die oxidation of organic halides. The oxidation of halomediyl compounds has been reviewed recently. ... 

The method is limited to activated halides which are stable to aUtoxide bases and aqueous acids. According to the discoverer, the Krdhnke oxidation is inferior to the Sommelet reaction for benzyl halides, especially those bearing electron-withdrawing groups, such as nitro. Some representative examples are shown in Scheme 6 and equations (6)-<12). As can be seen, the Krbhnke oxidation is an excellent method for the preparation of heterocyclic aldehydes which would otherwise be difficult to synthesize. The preparations of a phthalimidoketo aldehyde (equation 11) and benzene-l,3,S-tricarbalde-hyde (equation 12) are also noteworthy. 

Several unique heterocyclic fused-1,2,4-triazole structures have been published. Pyridine amination of 216 with O-mesitylenesulfonylhydroxylamine followed by condensation with various aryl and heterocyclic aldehydes and subsequent cyclization and oxidation gave triazolopyridines 217 <03TL1675>. Triazolopyridines 217 were utilized in the direct conversion to the triazolopyridine amides 218 with methylaluminoxane premixed with amines in a combinatorial library synthesis. A convenient synthesis of novel 4-(l,2,4-triazol-l-yl)-2-pyrazolines and their derivatives has been reported <03SC1449>. A novel triheterocyclic ring system, thieno[2,3-y][l,2,4]triazolo[l,5-a]azepines, has been published <03S1231>. 

The reaction is most important for the preparation of carbinols from certain aromatic and heterocyclic aldehydes and for the preparation of several aliphatic polyhydroxy compounds. In the normal Cannizzaro reaction the theoretical yield of alcohol is only 50% because half of the aldehyde is converted to the acid. A mixture of an aldehyde with excess formaldehyde, however, results in a dismutation in which most of the higher aldehyde is reduced formaldehyde is oxidized to sodium formate, viz., ... 

The reaction between o-phenylenediamine and an equimolar amount of an aromatic or heterocyclic aldehyde has been shown to proceed by initial formation of a monoanil (74). In the presence of oxidizing agents (e.g. nitrobenzene, which also acts as the solvent) this can form the 2-substituted benzimidazole. With two moles of aldehyde the bis-anil (75) forms, giving rise to a 1,2-disubstituted benzimidazole (Scheme 42). This aldehyde route to benzimidazoles is particularly suited to the synthesis of compounds with a heterocyclic group (e.g. 2-thienyl-, 2-pyridyl-) at C-2. Reaction of 2,2,4,4-tetrakis(trifluoromethyl)-l,3-dithietane with o-phenylenediamine gives 2,2-bis(trifluoromethyl)benzimidazoline (7430785). 

Under oxidative conditions, aldehydes will react with 1,2-arylencdiamincs. With an equimolar amount of any aromatic or (especially) heterocyclic aldehyde the initial product is a monoanil. In the presence of suitable... 

In the benzoin condensation, one molecule of aldehyde serves as an electrophile. If a carbanion is generated from protected cyanohydrins, a-aminonitriles or dithioacetals, it can react with electrophiles such as alkyl halides, strongly activated aryl halides or alkyl tosylates to form ketones. Amongst other electrophiles which are attacked by the above carbanions are heterocyclic A -oxides, carbonyl compounds, a,p-unsaturated carbonyl compounds, a,3-unsaturated nitriles, acyl halides, Mannich bases, epoxides and chlorotiimethyl derivatives of silicon, germanium and tin. 

Diaza-compounds. Phenacyl bromide reacts with 2-aminopyridine 1-oxide to yield 2-phenylimidazo[l,2-a]pyridin-3-ol (769) another derivative of this ring system, compound (771), is produced by the action of diphenylketen on the sulphilimide (770), dimethyl sulphide being eliminated.(6-Methyl-2-pyri-dyl)acetyl azide (772) forms the dihydroimidazo[3,4-a]pyridinone (773) on heating." Whereas l-methylpyrrole-2-aldehyde and other heterocyclic aldehydes react with tosylmethyl isocyanide to give oxazoles, e.g. (774), pyrrole-2-aldehyde affords the 6-azaindolizine (775). The action of potassium amide on the derivative (776) of 3-bromopyridine furnishes the pyrrolo[3,4-c]pyridine (777) by cyclization of an intermediate pyridyne." ... 

A study of QDC oxidation of heterocyclic aldehydes and carboxylic acids in AcOH-H2O supports a rate-determining decomposition of the chromate ester. The rate of oxidation of dimedone (DM) in HCIO4 is of first order in QDC, of order less than unity in DM and H+ ions, and increases with increasing dielectric constant. The mechanism postulated involves the formation of a complex between protonated Cr(VI) species and DM, which decomposes to a DM free radical and Cr(V) in a slow step followed by fast steps to give the products. The rate of oxidation of L-glutamic acid (Glu) in HCIO4 is first order in QDC and Glu, and increases with [H+] and the ionic strength. 

Cinnamyl cinnamate derivatives were obtained in good to excellent yields by esterification of a,j8-unsaturated aldehydes, including aromatic aldehydes, with cinnamyl bromides in the presence of DBU, K2CO3, THF, and f-BuOH using either atmospheric O2 or Mn02 as the oxidant and IV-heterocyclic carbene (NHC) as the catalyst. The use of 02 indicated that the path of the O2 oxidation via Breslow intermediate (119) (Scheme 12) differs from that for aldehyde oxidation by Mn02 via a tetrahedral intermediate (124) (Scheme 13). ... 

Oxidation of 4-acetoxy-l-methylisoquinoline (76) with selenium dioxide produced the corresponding 1-carboxaldehyde, which upon acid hydrolysis yielded the 4-hydroxy derivative. Treatment of heterocyclic aldehydes with thio-semicarbazide produced the desired thiosemicarbazones. In general, the 4-substituted derivatives were less effective than (1) as antineoplastic agents against Sarcoma 180 ascites cells in mice however, the sodium salt of the 4-hydroxy derivative was considerably more efficacious than (1) against the L-1210 lymphoma. 

Aldehydes are organic compounds that have a carbonyl group (-CHO) on the terminal carbon atom of a hydrocarbon chain or attached to an aromatic or heterocyclic ring. The aliphatic aldehydes are useful as chemical intermediates in synthetic chemistry where oxidation produces the corresponding acid and reduction yields the alcohol structure. Condensation reactions of the aldehydes with phenol, urea, or melamine yields useful resinous products. A useful heterocyclic aldehyde, furfural or 2-furaldehyde (the aldehyde group attached to the 2 position on the furan ring), is both a reactant in synthetic chemistry and has several specialized uses as a solvent. 

The mechanisms of pyridine formation are poorly characterized. Vemin and Parkanyi [12] have proposed three mechanisms. The first two mechanisms are dependent upon aldol condensations to yield unsaturated aldehydes with side groups. Reaction then with ammonia or an amino add and ring closure would yield a nitrogen-containing heterocyclic. The oxidation of this heterocyclic would result in the formation of a pyridine. The third pathway involves the reaction of dialdehydes with ammonia followed by dehydration to produce pyridines. 

---