1- Acylimidazoles aldehydes

A-Acylimidazoles are easily reduced to the corresponding aldehydes with LiAlH4 in THF or ether as solvent.[1] Thus, aliphatic, conjugated aliphatic, aromatic, conjugated aromatic, and heteroaromatic aldehydes can all be obtained in this way in moderate to high yields. 

Irradiation of 1-acyl-1,2,4-triazoles, contrary to A-acylimidazoles affords no photo-Fries products, but instead forms aldehydes and other products via the corresponding acyl radicals.t9]... 

Much work in the review period has concerned enantioselective substitution in five-membered heterocyclics. The enantioselective alkylation of some pyrroles by unsaturated 2-acylimidazoles catalysed by the bis(oxazolinyl)pyridine-scandium(in) triflate complex (31) has been reported.39 Compound (33) is formed in 98% yield and 94% ee from the 2-acylimidazole (32) and pyrrole at —40 °C. A series of enantiomer- ically pure aziridin-2-ylmethanols has been tested as catalysts in the alkylation of /V-mclhylpyrrolc and (V-methylindole by ,/l-unsalura(cd aldehydes.40 Enantiomeric excesses of up to 75% were observed for the alkylation of /V-mcthylpyrrole by ( >crotonaldehyde using (2.S ,3.S )-3-mclhylazirin-2-yl(diphenyl)methanol TFA salt as catalyst to form (34). 

Peracids can also be prepared from reaction of hydrogen peroxide with acyl halides, anhydrides, amides, dialkyl phosphates, N-acylimidazoles, aromatic aldehydes, lipase catalysis and esters (Figure 2.38).100-107... 

The synthesis of aldehydes [C5] can also be accomplished by controlled reduction of acylaziridines 3.178 [BK5] or of acylimidazoles 3.179 [W3] by LAH in Et20 at -10°C, by LTBA or by Red-A1 in [H3, M3] R can be aliphatic or aromatic (Figure 3.66). The N-methoxy-N-methylcarboxamides 3.180 are also cleanly reduced to aldehydes by LAH in excess in THF at low temperature or by DIBAH in THF at 0°C. In many cases, the latter reagent does not lead to formation of alcohols as byproducts resulting from a subsequent reduction of the aldehyde [NWl]. This behavior can be understood by the stabilization through chelation of the lithium or aluminum intermediate (Figure 3.66). a,p-Unsaturated aldehydes may also be prepared by this method, using DIBAH in THF [BS8, NBl]. 

The major classes of carbonyl compounds include aldehydes, ketones, carboxamides, esters, carboxylic acids and anhydrides, and carbonyl halides (acyl halides). These groups differ in the identity of the substituent X on the carbonyl group. At this point we concentrate on these examples, but a number of other carbonyl derivatives have important roles in synthetic and/or biological reactions. These other compounds include acyl cyanides, acyl azides, A-acylimidazoles, 0-aryl esters, and thioesters. The carbonyl compounds are arranged below in the order of the increasing reactivity toward nucleophilic addition. 

Ried et ah551 recently found a generally applicable aldehyde synthesis in the hydrogenolytic fission of l-acyl-3,5-dimethylpyrazole by lithium aluminum hydride, a reaction that takes place with very good yields in ether at 0-20°. An appreciably better method still is to use the same hydride in ether or tetrahydrofuran to reduce the corresponding 1-acylimidazoles, which are readily obtained from the free acids and l,l -carbonyldiimidazole with 0.25 mole of hydride per mole of acylimidazole the reduction is complete in 30-60 min at —20°,552 and it is an advantage of the method that it can be carried out entirely in one vessel without isolation of the acylimidazole intermediate. 

Aldehydes and Ketones from Carboxylic Acids. Reduction of the derived acylimidazole (2) with Lithium Aluminum Hydride achieves conversion of an aliphatic or aromatic carboxylic acid to an aldehyde (eq 6). DiisobutyUduminum Hydride has also been used, allowing preparation of a-acylamino aldehydes fromiV-protected amino acids. Similarly, reaction of... 

A-Acylimidazoles are even more easily hydrolysed than A-acylpyrroles, moist air is sufficient. The ready susceptibility to nucleophilic attack at carbonyl carbon has been capitalised upon commercially available I,r-carbonyldiimida-zole (CDI), prepared from imidazole and phosgene, can be used as a safe phosgene-equivalent, i.e. a synthon for 0=C, and also in the activation of acids for formation of amides and esters via the A-acylimidazole. In another application, A-acylimidazoles react with lithium aluminium hydride at O C to give aldehydes, providing a route from the acid oxidation level. 

Aldehydes from carboxylic acids via 1-acylimidazoles s. 18, 127 COOH CHO... 

Overall, this coupling substrate showed the greatest flexibility in the coupling of arene heterocycles with a wide variety of 3-substituted (Ri-substituted) A - Pr-substituted a,P-unsaturated 2-acylimidazoles. The resulting acyl imidazolides could be converted in straightforward fashion to either aldehyde, ketone, acid, ester, or amide moieties using a one-pot two- or three-reaction sequence (not shown in scheme). ... 

Aryltrifluoromethyl ketones are prepared by reaction of an aryl-lithium with a,a,a-trifluoro-N,N-dimethylacetamide. 2-Acyloxypyridines and N-acylimidazoles, " in conjunction with trifluoroacetic acid, acylate arenes in good yield without the need for a classical Friedel-Crafts catalyst or a preformed mixed anhydride. However, imidazole in trifluoroacetic anhydride is reported to form 2-aryl-Af,JV -diacyl-4-imidazolines with arenes reactive towards electrophilic attack. These adducts are readily hydrolysed by sodium hydroxide to the corresponding aldehyde [equation (14)]. This sequence may offer advantages over the Vilsmeier method of formylation, in that the aldehyde is introduced in a protected form. 

Acylimidazoles and Nucleophiles. Acylimidazoles are readily prepared from the parent carboxylic acids by reaction of the derived acid chloride with imidazole or directly using N,N -Carbonyldiimidazole. These intermediates react smoothly with a variety of nucleophiles including Grignard reagents (eq 3), Lithium Aluminum Hydride (eq 4), and nitronates (eq 5). At —20 ""C, aroylimidazoles can be reduced to the corresponding aldehydes in the presence of an ester function. ... 

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