Ethyl orthoformate, reaction with

Some weak electrophilic reagents, which are usually inert toward azoles, also react with quaternized azoles. Diazonium salts yield phenylhydrazones (Scheme 48) in a reaction analogous to the Japp-Klingemann transformation of /S-keto esters into phenylhydrazones in the dithiolylium series illustrated the product has bicyclic character. Cyanine dye preparations fall under this heading (see also Section 4.02.1.6.5). Monomethine cyanines are formed by reaction with an iodo quaternary salt, e.g. Scheme 49. Tri- and penta-methinecar-bocyanines (384 n = 1 and 2, respectively) are obtained by the reaction of two molecules of a quaternary salt with one molecule of ethyl orthoformate (384 n = 1) or/S-ethoxyacrolein acetal (384 n =2), respectively. 

Ethoxy-2-cyclohexenone has been prepared by reaction of the silver salt of dihydroresorcinol with ethyl iodide and by the reaction of dihydroresorcinol with ethyl orthoformate, ethanol and sulfuric acid." The acid-catalyzed reaction of dihydroresorcinol with ethanol in benzene solution utilized in this preparation is patterned after the procedure of Frank and Hall. ... 

As stated previously, 3-monoethyl enol ethers can be prepared from A" -3,17-diketones and A -3,20-diketones by warming with stoichiometric amount or a large excess of ethyl orthoformate at room temperature. With 2,2-dimethoxypropane, the 3-methyl enol ether is the only reaction product even at high temperatures. 

Unsubstituted quinazoline 3-oxide was prepared in an attempt to react quinazoline with hydroxylamine. This reaction gave a product of variable composition, but when an acetone solution was heated in a sealed tube it gave quinazoline 3-oxide. The oxide is more conveniently prepared, in excellent yield, from o-aminobenzaldehyde oxime and ethyl orthoformate. This method appears to be of general use and has been used for the preparation of 4-methylquinazoline... 

The methiodide and ethiodide of 4-methylcinnoline possess methyl groups which condense easily with aldehydes, and even with ethyl orthoformate,to give polymethine derivatives. These reactions, particularly that with the ortho ester, suggest that the salts have structure 55 (R = Me or Et, R = Me). The methiodide of 3-methylcinnoline also reacts with aldehydes, although more slowly, but no reaction with ethyl orthoformate has been reported. Although 55 (R = Me) appears to be the most likely structure for the product, the 4-methyl group may direct the quatemization on and,... 

Reaction of 2,4-xylidine with methylamine and ethyl orthoformate leads to the amidine 119 condensation of that product with a second mole each of orthoformate and 2,4-xylidine gives the scabicide amitraz (120) [29]. 

To a Soiution of 3.0 g of 16/3-ethylestra-4-ene-3,17-dione dissoived in 150 ml of dioxane, are added 15 g of ethyl orthoformate and 0.1 g of p-toluenesuifonic acid, followed by stirring for 2 hours at room temperature. The reaction solution is poured into 300 ml of a 5% aqueous solution of Sodium hydrogen carbonate and the resultant mixture is extracted with ether. The ether layer is washed with water and dried, followed by evaporation of the solvent to give Crude crystals of 3-ethoxy-18/3-ethylestra-3,5-diene-17-one. The crystals are recrystallized from ether to give 30 g of the compound melting at 114°C to 115°C. 

Ammonium acetate, reaction with tn-ethyl orthoformate to give form-amidine acetate, 46, 39 Ammonium p chlorophenyldithiocarba mate, 46, 21... 

Grignard reaction, (Continual) with ethyl formate, 16, I r with ethyl orthoformate, 16, 41 with water, 11, 84... 

The fact that reaction can be made to go with (25), but not with the simple R OH, is due to the ASe (c/ p. 36) value for the former being more favourable than that for the latter, which involves a decrease in the number of molecules on going from starting material to product. Both aldehydes and ketones that are otherwise difficult to convert into acetals may often be transformed by use of orthoesters, e.g. HC(OEt)3, triethoxymethane ( ethyl orthoformate ), with NH Cl as catalyst. 

Grignard reagents can also act as sources of negative carbon in displacement reactions, e.g. in the synthetically useful reaction with triethoxymethane (ethyl orthoformate, 58) to yield acetals (59) and, subsequently, their parent aldehydes (60) ... 

The synthesis of the corresponding naphthyridone scaffold was carried out according to the methods reported by Chu et al. [12] and Sanchez et al. [13]. Namely, the hydrolysis of ethyl 2,6-dichloro-5-fluoronicotinate (3) [14] followed by reaction with thionyl chloride results in the formation of 2,6-dichloro-5-fluoronicotinyl chloride (4). Treatment of this compound with monoethyl malonate in THF under n-butyllithium followed by acidification and decarboxylation gives rise to ethyl 2,6-dichloro-5-fluoronicotinylacetate (5). Reaction of compound 5 with ethyl orthoformate in acetic acid followed by cyclopropylamine results in the formation of 3-cyclopropylamino-2-(2,6-dichloro-5-fluoronicotinyl)acrylate (6), the cyclization reaction of which under NaH/THF gives rise to the required ethyl l-cyclopropyl-6-fluoro-7-chloro-l,4-dihydro-4-oxo-l,8-naphthyridine-3-carboxylate (7), as shown in Scheme 3. 

The synthesis of compound 27 was initiated with the treatment of ke-toester 29, reported by Yoshida et al. [25], with ethyl orthoformate in acetic acid, followed by reaction with (l.R,2S)-2-fluoro-1-cyclopropylamine p-toluenesulfonic acid salt in the presence of triethylamine to yield an enam-inoketoester intermediate, cyclization of which under NaH in dioxane yields the 5-nitroquinolone derivative (30). Reduction of the nitro group of compound 30 followed by acid hydrolysis provides compound 27 via the amino-quinolone derivative (31), according to Scheme 7. 

Snyder and Jones obtained ethyl N-(3-chlorophenyl)aminomethyl-enemalonamate (244) in 77% yield when 2 mol of 3-chloroaniline was reacted with 1 mol of diethyl malonate and 1 mol of ethyl orthoformate at 160-165°C. The ethanol formed during the reaction was distilled off (46JA1253). 

Wolfbeis investigated the reactions of amines and orthoesters with different CH-acid molecules (81CB3471). When the reactions of aniline, ethyl orthoformate, and dialkyl malonates (2 mol) were carried out at 130-140°C for 4 hr, phenylaminomethylenemalonamates (245) were obtained (81CB3471). Similar reactions with aliphatic amines were unsuccessful. Phenylaminomethylenemalonic acid could not be prepared in the reactions of aniline, methyl orthoformate or orthoacetate, and malonic acid. When these reactions were carried out in 2-propanol, only amidines (246) were obtained. 

The uncatalyzed reactions between anilines, ethyl orthoformate, and diethyl malonate afforded ethyl arylaminomethylenemalonamates (252) in 67-85% yields (87SC549). However, if the malonate was first reacted with ethyl orthoformate and acetic anhydride in the presence of a catalytic amount of ZnCl2 at boiling temperature for 5 hr and aniline was then added to the reaction mixture, reflux being maintained for 0.5 hr, arylaminomethylenemalonates (253) were obtained in 52-85% yields. 

Arylazo-l-naphthylamines were first reacted with ethyl orthoformate in boiling xylene for 2 hr diethyl malonate and piperidine were then slowly added to the reaction mixture over a period of 15-20 min. The resulting... 

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