Aldehyde orthoformic acid ester

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

On the other hand, 1,1,1-trisubstituted alkanes behave similarly to aldehydes, yielding pyrjdium salts (128) with identical substituents in positions 2 and 6. Thus, Dorofeenko and co-workers condensed 2 moles of acetophenone with 1 mole of benzotrichloride in the presence of perchloric acid obtaining 2,4,6-triphenjdpjTylium perchlorate with 1 mole of ethyl orthoformate, they obtained 2,6-diphenyl-pyrylium perchlorate (57) from o-hydroxyacetophenone, ortho-formic ester and perchloric acid, 4-ethoxybenzopyrylium perchlorate was formed. 

A completely different concept13 makes use of a highly reduced bilane 5 which is oxidatively cyclized to an isobacteriochlorin 6 with copper(II) acetate. The ring closure is initiated by ester cleavage with trifluoroacetic acid and decarboxylative formylation with trimethyl orthoformate to yield a dialdehyde. One of the aldehyde functions forms the desired methine bridge whereas the other is lost during cyclization. 

For instance, 2-methylpropene reacted with acetic acid at 18°C in the presence of Al-bentonite to form the ester product (75). Ion-exchanged bentonites are also efficient catalysts for formation of ketals from aldehydes or ketones. Cyclohexanone reacted with methanol in the presence of Al-bentonite at room temperature to give 33% yield of dimethyl ketal after 30 min of reaction time. On addition of the same clay to the mixture of cyclohexanone and trimethyl orthoformate at room-temperature, the exothermic reaction caused the liquid to boil and resulted in an almost quantitative yield of the dimethyl ketal in 5 min. When Na- instead of Al-bentonite is used, the same reaction did not take place (75). Solomon and Hawthorne (37) suggest that elimination reactions may have been involved in the geochemical transformation of lipid and other organic sediments into petroleum deposits. 

Carbon atom 2 of the oxazole ring is also supplied by aldehydes in their reaction with a- (hydroxylamino) ketones, which proceeds in the presence of sulfuric acid and acetic anhydride (equation 109). Three further oxazole syntheses involving incorporation of a C(2) fragment are the condensation of triethyl orthoformate with the hydrochlorides of a-aminoacetophenones (equation 110), the reaction of acyl chlorides with a-azido ketones or a-azido esters in the presence of triphenylphosphine (equation 111), and the preparation of 2-aminobenzoxazole and benzoxazoleimines from o-aminophenols and cyanogen bromide (equation 112). 

Acetals are readily hydrolyzed by dilute mineral acids however, the yields are not always satisfactory. These substances are not affected by alkaline reagents. The sensitive JZ-glyceraldehyde acetal is converted to its aldehyde in 80% yield by the action of dilute sulfuric acid under mild conditions. Other procedures are illustrated by the treatment of acetals which are formed by the interaction of Grignard reagents and orthoformic esters (method 165). 

Under carefnlly optimized experimental conditions, dialkyl 2,2-diethoxyethylphosphonates react with chlorine in reflnxing CCI4 under UV irradiation to provide dialkyl l,l-dichloro-2,2-diethoxyethylphosphonates. 5 These products can also be prepared in quantitative yield by reaction of diethyl 1,1-dichloro-1-formylmethylphosphonate with orthoformic esters in the presence of sulfuric acid. However, subsequent hydrolysis of these acetals gives modest yields of the corresponding aldehydes (30-40%). ... 

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