Ethyl orthoformate

The solution is placed in a 3-I. flask fitted with an 80-cm. fractionating column (Note 4) and the excess chloroform and most of the alcohol are distilled off on a steam or water bath. The distillate is caught in a 2-1. suction flask protected from moisture by a drying tube. This distillation requires five or six hours. A mixture of chloroform and alcohol, weighing about 2000 g., is recovered and saved for the next run (Note 3). The liquid remaining in the flask is decanted from the small amount of salt which has separated, into a Claisen flask with a 30-cm. fractionating column (Note 5). The mixture is distilled at atmos- 

After the first run, 400 g. of chloroform and enough absolute alcohol (800-1000 cc.) are added to the recovered chloroform-alcohol mixture to give a total volume of 3 1. The sodium is then added as before. After the excess of chloroform and alcohol has been distilled through the fractionating column, the intermediate fraction from the previous run is added before fractionating. The yield from such a run is about 200 g. (45 per cent of the theoretical amount). 

Enough chloroform must be used to keep the solution from being alkaline at the end of the reaction. 

If care is taken to prevent moisture from getting into the recovered alcohol-chloroform mixture, this mixture may be used repeatedly. After it has been used four or five times, the yield begins to fall. 

The long fractionating column used by Clarke and Rahrs 

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RCHO + RCHO —> RCOOCHjR 3. From ethyl orthoformate and the Grignard reagent, for example CsH aMgBr + CH(0C3H3)3 —... 

The ethyl orthoformate required in this preparation may be prepared by the action of sodium upon a mixture of chloroform and dry alcohol ... 

To a mixture of 250 ml of ether and 3 moles of freshly distilled acrolein ivere added about 3 moles of bromine at a rate such that the temperature could easily be maintained between -30 and -90°C (bath of dry-ice-acetone or liquid Nj). After persisting of the browncolour, the temperature was allowed to rise to 0°C. Freshly distilled ethyl orthoformate (3.25 moles) and 96% ethanol (30 ml) were added. 

Carbocyanines with three methine groups can be prepared using Pvo equivalents of selenazolium quaternary salt and one equivalent of ethyl orthoformate in pyridine solution (53). 

This method, however, is not industrially practical because a large amount of dehydrating agent, such as ethyl orthoformate, is required to remove water formed in the reaction. Because water is an inhibitor of the reaction, the reaction system has to be kept under substantially anhydrous conditions. 

Barbiturates (Veronal. Barbital, Luminal, Amytal), ethyl orthoformate, and other chemicals are produced commercially from sodium ethoxide. 

There is also the possibility of removing the 2-oxo group by ring cleavage and subsequent recyclization. Lumazine can be hydrolyzed by strong alkali to 2-aminopyrazine-3-carboxylic acid (153) which is converted first into the amide (154) and then cyclized by ethyl orthoformate into pteridine-4-one (155 equation 47) (51JCS474). 

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. 

Compounds i, ii, and iii can be prepared by an acid-catalyzed reaction of a diol and the cycloalkanone in the presence of ethyl orthoformate and mesitylenesul-fonic acid. The relative ease of acid-catalyzed hydrolysis [0.53 M H2SO4, H2O, PrOH (65 35), 20°] for compounds i, iii, acetonide, and ii is C5 C7 > ace-... 

Ethyl orthoformate [122-51-0] M 148.2, b 144 /760mm, d 0.892, n 1.391. Shaken aqueous 2% NaOH, dried with solid KOH andd distd from sodium through a 20cm Vigreux column. 

Acrolein Acetal (ir, i) By treating acrolein with ethyl orthoformate in the presence of ammonium nitrate. Fischer and Baer, Helv. Chim. Acta i8, 514 (1935). 

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. ... 

In the sjmthesis of evodiamine effected by Asahina and Ohta,i N-methylanthranilic acid was converted by ethyl chloroformate into N-methylisatoic anhydride, which, on treatment with 3- -aminoethylindole, furnished 3-/3-o-methylaminobenzoylaminoethylindole (III), and this with ethyl orthoformate at 175-180° gave dZ-evodiamine, m.p. 278°, convertible by boiling alcoholic hydrogen chloride into Zsoevodiamine, m.p. 147°, as shown above. 

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. 

Ji-Methoxy-ll, 11-ethylenedioxy-lS-methylestra-1,3,5(lO)-tnene. A solution of (+)3-methoxy-18-methylestra-l,3,5(10)-trien-17-one (5 g) dissolved in ethylene glycol (5 ml) and ethyl orthoformate (10 ml) containing />-toluenesulfonic acid (0.3 g) is heated under reflux for 2 hr in a nitrogen atmosphere. The resulting solution is diluted with methylene chloride and washed with dilute sodium bicarbonate and water. The organic phase is dried over sodium sulfate and evaporated to dryness in the presence of a trace of pyridine. Trituration of the residue with petroleum ether yields 4.7 g (82 %) of the pure ketal. 

Steroidal 17-cyanohydrins are relatively stable towards chromium trioxide in acetic acid (thus permitting oxidation of a 3-hydroxyl group ) and towards ethyl orthoformate in ethanolic hydrogen chloride (thus permitting enol ether formation of a 3-keto-A system ). Sodium and K-propanol reduction produces the 17j -hydroxy steroid, presumably by formation of the 17-ketone prior to reduction. ... 

Methylene, 287 Pivaldehyde Acetal, 289 Acetonide, 289 Cyclohexylidene. 289 Diphenylmethylene, 289 Ethyl Orthoformate, 290 Diisopropylsilylene Derivative, 290... 

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... 

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