Aldehydes from formamides

Luche and coworkers extended their studies on the applications of ultrasound to synthesis to include a variety of systems. Among these applications are the syntheses of lithioorganocuprates(ll), of aldehydes from formamides(12), of organozinc intermediates(13),... 

Formyl complexes are characterized by distinct spectroscopic features. The most frequently used diagnostic probe has been H NMR. Chemical shifts in the 8 12-17 range (several ppm downfield from normal aldehyde or formamide H-NMR resonances) (69) are observed. However, since chemical shifts measured in the presence of trialkylborane by-products can show marked temperature dependence (32, 38, 47, 66), absolute values must be treated with caution. 

Radical nucleophile oxidation based on one-electron oxidation, known as the Minisci reaction, is employed for the functionalization of /V-heterocycles with acidic hydrogen peroxide in the presence of iron(II) salts (Figure 3.112).472 A range of A-heterocycles (pyridines, pyrazines, quinolines, etc.) which are activated towards attack by nucleophilic radicals when protonated are suited to this chemistry. The Minisci reaction is suitable for the preparation of carboxylic amides (from formamide), carboxylic esters (from pyruvic esters via a hydroxyhydroperoxide), aldehydes (from 1,3,5-trioxane) and alkylated pyridines (either from carboxylic acids or from alkyl iodides in dimethyl sulfoxide).473 The latter reaction uses dimethyl sulfoxide as the source of methyl radical (Figure 3.112). 

Aldehydes can also be obtained from Grignard reagents by reaction with formamides, such as A-formylpiperidine. In this case, the initial adducts are stable and the aldehyde is not formed until hydrolysis during workup. 

Anthrapyrimidine and its substituted derivatives are obtained by condensation of 1-aminoanthraquinone (or its derivatives) with formamide or aqueous form-aldehyde/ammonia in the presence of an oxidant, such as ammonium vanadate or m-nitrobenzosulfonic acid. A newly developed, more simple route proceeds via formamidinium chloride, which is prepared from 1-aminoanthraquinone with di-methylformamide and thionyl chloride or phosphorus oxychloride. Cyclization in a solvent in the presence of ammonium acetate affords the desired product ... 

Fused cyclic system 340 can be obtained by type (i) reaction through the reduction of the nitro aldehyde intermediate 339 and its sequential cyclization in acetic acid. Alternate type (iii) process starts from the corresponding formamide 341 that can be cyclized with phosphorus oxychloride by a Bischler-Napieralski reaction (Scheme 72 (1994JHC1033)). 

The largest quantum yield obtained from the aldehyde oxidation of Equation 45 was seen with tolualdehyde using absolute diethyl formamide as a solvent (45). In this instance, the quantum yield is 6 x 10-3, which is about twentyfold less than obtained with the bacterial luciferase enzymes. 

Many noticeable examples of chiral Lewis base catalyzed allylation of carbonyl compounds have also appeared. Iseki and coworkers published a full paper on enantioselective addition of allyl- and crotyltrichlorosilanes to aliphatic aldehydes catalyzed by a chiral formamide 28 in the presence of HMPA as an additive [41]. This method was further applied to asymmetric allenylation of aliphatic aldehydes with propargyltrichlorosilane [40]. Nakajima and Hashi-moto have demonstrated the effectiveness of (S)-3,3 -dimethyl-2,2 -biquinoline N,AT-dioxide (29) as a chiral Lewis base catalyst for the allylation of aldehydes [42]. In the reaction of (fs)-enriched crotyltrichlorosilane (54 , E Z=97 3) with benzaldehyde (48), y-allylated anfi-homoallylic alcohol 55 was obtained exclusively with high ee while the corresponding syn-adduct was formed from its Z isomer 54Z (fs Z= 1 99) (Scheme 6). Catalytic amounts of chiral urea 30 also promote the asymmetric reaction in the presence of a silver(I) salt, although the enantioselectivity is low [43]. 

The reaction of -halo carbonyl compounds with primary amides is appropriate for oxazoles containing one or more aryl groups . Ureas form 2-aminooxazoles. Formamide can be used resulting in a free 2-position in the oxazole. A convenient synthesis of 5-substituted-4-cyanooxazoles 223 is based on the condensation of -hydroxy—cyanoenamines 222 with trimethyl orthoformate (Scheme 109). The cyanoenamine intermediates 222 are derived from Lewis acid-catalyzed Passerini reactions between /-butyl isonitrile and aldehydes <2002S1969>. 

This type of reaction with A N-disubstituted formamides, giving aldehydes, was an early application of Grignard reagents, sometimes known as the Bouveault reaction [A]. Dimethylformamide and N-methylformanilide, PhN(Me)CHO, have been most commonly used, but more recently iV-formylpiperidine and 2-(/V-formylmethylamino)pyridine have been recommended examples are listed in Table 6.5, and a recent example of the traditional procedure follows. It should be noted that these reactions are subject to a number of side-reactions [A]. One useful one is the formation of enamines by elimination from the initial adduct [9] ... 

Selenophene-3-aldehyde has been obtained by the Sommelet reaction of 3-bromomethylselenophene (obtained from 3-methyl-selenophene and A-bromosuccinimide), by reaction of dimethyl-formamide with 3-lithioselenophene (obtained by lithium-iodine exchange at — 60°C),74 and by reduction and subsequent hydrolysis of selenophene-3-carbonitrile.75... 

Water-in-oil gel emulsions were tested in enzymatic aldolization of selected N-Cbz-amino aldehydes (Figure 19.3), N-Cbz-3-amino propanal (4), N-Cbz-glycinal, (5), (S)-N-Cbz-alaninal (6), and (R)-N-Cbz-alaninal (7) catalyzed by RAMA and L-rham-nulose-1-phosphate aldolase (RhuA) and L-fuculose-1-phosphate aldolase (FucA) from Escherichia coU [27,28]. The largest differences between conventional dimethyl formamide (DMF)/water co-solvent systems and gel emulsions were observed with RAMA and FucA catalysts (Figure 19.3). The emulsion media enhanced the catalytic efficiency of RAMA towards the N-Cbz amino aldehydes tested three, five. 

Acid Amides can be produced by acylating ammonia with esters, acid anhydrides, or the acids themselves (above 100 °C) an important product is formamide from methyl formate. Alternatively acid amides can be synthesized by reacting acid halides with ammonia. Catalytic hydrogenation converts the acid amides to primary amines. Ammonia and aldehydes or ketones are the basis for different stable products. With formaldehyde hexamethylenetetramine (urotropine) is obtained with acetaldehyde, ammono acetaldehyde with benzaldehyde, hydrobenzamide with ethylene and propylene oxides, aqueous ammonia reacts to form ethanol- or propanolamine. 

From the interaction at low temperatures in basic medium of an aldehyde or ketone and tosylmethyl isocyanide ( tosmic ), iV-(l-tosyl-l-alkenyl)formamides are formed. When these are dehydrated they produce 1-isocyano-l-tosylalkenes (66) which react with primary amines to form imidazoles in high yields (Scheme 35) (79RTC258). 

This is made from A -(4-isoxazolyl)formamide by the above general procedure with the modification that the intermediate a-amino-a,j8-unsaturated aldehyde (7) (R, = H) precipitates. In consequence, the catalyst is not filtered... 

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