Drying formamide

The determination of the molecular weight of animal cell RNA, using electrophoresis on exponential polyacrylamide gels under fully denaturing conditions, has been described. Effects due to RNA secondary structure are fully suppressed if dry formamide and high temperatures are used.177... 

While the ether solution of the aminoketone is drying, formamide (35 mL) is added to a 300-mL, three-necked flask, which is fitted with an air-cooled condenser, a pressure-equalizing dropping funnel that is topped with an inert atmosphere inlet tube, and a thermometer, which extends into the liquid. The formamide is heated with stirring to 180°C under a slow stream of dinitrogen, which exhausts through the top of the condenser. 

Formamide. Commercial formamide may contain excess of formic acid. It is purified by passing ammonia gas into the mixture until a slight alkaline reaction is obtained. The ammonium formate thus formed is precipitated by the addition of acetone the filtrate, after drying over anhydrous magnesium sulphate, is distilled under reduced pressure. Pure formamide has b.p. IO571I mm. 

Formamide (specific conductance 2 x 10 ohnr cnr ) of low water content was dried by passage through a column of 3A molecular sieves, then deionized by treatment with a mixed-bed ion-exchange resin loaded with H" " and HCONH" ions (using sodium formamide in formamide)[Notley and Spiro J Chem Soc (B) 362 1966. ... 

A mixture of 3.18 g (10 mmoles) of 17 -hydroxy-2-hydroxymethylene-5a-androstan-3-one, 20 ml dry dimethyl formamide and 0.3 g (13 mmoles) of sodium hydride is stirred for 0.5 hr at room temperature under nitrogen. A total of 1.51 g (12.5 mmoles) of redistilled allyl bromide is added and the mixture is stirred for 1 hr on the steam bath. Aqueous potassium hydroxide (2 g in 5 ml of water) is added and stirring is continued for 1 hr on the steam bath. The reaction mixture is diluted with 50 ml of methylene dichloride followed by careful addition of 300 ml of water. The organic phase is separated and the aqueous phase is again extracted with 50 ml of methylene dichloride. The combined extracts are washed with water, dried over sodium sulfate, filtered and chromatographed on 200 g of silica gel. Elution with pentane-ether (4 1) provides 2a-allyl-17j -hydroxy-5a-androstan-3-one 0.85 g (26%) mp 118-119° [aj 14° (CHCI3), after crystallization from ether-hexane. 

Formamide is distilled under vacuum before use. /-Butyl alcohol may be dried by distillation from sodium or calcium hydride (3 g/100 ml). All other reagents should be dry. 

As described In U.S. Patent 3,023,146, in a round-bottomed flask were placed 35 g of 2-propionyl phenothiazine (0.14 mol) 7 g of 50% sodium hydride in mineral oil (0.14 mol), and 240 cc of dimethyl formamide dried over sodium hydride. The resultant solution was stirred at room temperature for 2 hours, and then 88 g (0.56 mol) of trimethylene chlorobromide wes added at once. 

To 6a-fluoro-16a-hydroxy-hydrocortisone 21-acetate, described by Mills et al, J. Am. Chem. Soc., volume 81, pages 1264 to 1265, March 5, 1959, there was added acetic anhydride in dry pyridine. The reaction mixture was left at room temperature overnight and was then poured with stirring into ice water. The resulting precipitate was filtered, washed with water and crystallized from acetone-hexane to give 6a-fluoro-16a-hydroxy-hydrocortisone-16a,21-diacetate. This was reacted with methane-sulfonyl chloride in dimethyl formamide in the presence of pyridine at 80°C for 1 hour. The mixture was cooled, diluted with water and extracted with ethyl acetate. The extract was washed with water, dried over anhydrous sodium sulfate and the ethyl acetate was evaporated. By recrystallization of the residue from acetone-hexane there was obtained 6a-fluoro-A <" -pregnadiene-16o ,17a,21-triol-3,20-dione 16a,21 diacetate. 

To the mixture of 85.5 g ethyl a-(3chloro-4.aminophenyl)-propionate hydrochloride, 142 g sodium carbonate and 600 ml dimethyl formamide, 107 g 1,4room temperature. The mixture is filtered, the filtrate evaporated in vacuo, the residue is triturated with hexane, the mixture filtered, the residue washed with petroleum ether and the filtrate evaporated. The residue is combined with 280 ml 25% aqueous sodium hydroxide and the mixture refluxed for 8 hours. After cooling, it is diluted with water, washed with diethyl ether, the pH adjusted to 5 to 5.2 with hydrochloric acid and extracted with diethyl ether. The extract is dried, filtered, evaporated and the residue crystallized from benzene-hexane, to yield the a-(3-chloro-4-pyrrolinophenyl)-propionic acid melting at 94°C to 96°C. 

A mixture of 4-carbamoyl-4-N-anilinopiperidine and formamide is heated for 12 hours at 170°C. After cooling, the reaction mixture is divided between 100 parts water and 900 parts chloroform. The organic layer is separated, dried over MgSO, filtered and the filtrate is evaporated. The semisolid residue is stirred in ethyl acetate. The undissolved part is filtered off, washed with ethyl acetate, and dried, yielding 1-oxo-4-phenyl-2,4,8-triazaspiro-(4.5)decane. 

A. N,N-Dimeihyljormamide-dimelhyl sulfate complex. In a 500-ml. four-necked flask equipped with mechanical stirrer, reflux condenser with calcium chloride drying tube, dropping funnel, and thermometer is placed 73 g. (1.0 mole) of dimethyl-formamide, and 126 g. (1.0 mole) of dimethyl sulfate is added dropwise with stirring at 50-60° (Note 1). After the addition is complete, the mixture is heated for another 2 hours at 70-80°. The dimethylformamide complex forms as a viscous, colorless or pale yellow ether-insoluble oil. 

A mixture of jV-[(2-benzyl-3-methyl)phenyl]formamide (24. R1 = R3 = R4 = H R2 = Me 15 g, 68 mmol) in PPA (120 g) and POC1, (32 g. 208 mmol) was stirred at 120"C for 1.5 h. The mixture was cooled, diluted with cold H20. and basified by addition of aq KOH. The alkaline mixture was extracted with Et20, the extracts were dried (MgS04), and evaporated to give the crude product as an oily residue, which was purified by distillation under reduced pressure (bp 110 Q0.025 Torr). The distillate solidified on cooling to give the product as yellow needles yield 6g (43%) mp 68 C. 

C. MEDINA. The crude methylenedi(nitro-formamide) is pressed dry on the filter, stirred into lOSml of formic acid, and the paste allowed to stand overnight. The next day the soln is filtered thru an acid-proof flit, the formic acid and w removed by codistn with xylene, and the crude MEDINA, which seps as a sand, filtered and dried over paraffin and NaOH in a vacuum yield 80—100% based on methylene diform-amide, mp 98—103°. The crude MEDINA is recrystd from 2-nitropropane or et chloride iso-Pr ale 9 1, mp 104-059 (Ref 11, p 54). This prepn is also covered in Ref 20... 

Perfluoroalkyl carbanions, generated by reversible nucleophilic addition of a fluoride anion to fluoroalkenes, react with dry benzenediazonium chloride in dimethyl formamide, giving phenylazoperfluoroalkanes in 41-53% yield (Dyatkin et al., 1972). The dianion obtained from 1,2-dinitrobenzene with dipotassium cyclo-octatetraenide reacts in a complex way with arenediazonium salts, forming 4-aryl-azo-2-nitrophenol in 46-58% yield (Todres et al., 1988). 

The three-necked flask is charged with 750 ml. of formamide, 25 ml. of water, and 50 g. of ammonium chloride (Note 2). The mixture is heated to 180-190° in an oil bath, and 400 g. (3.02 moles) of 4,4-dimethoxy-2-butanone (Note 3) is added dropwise with stirring over the course of 6 hours (Note 4). The flow of cooling water in the reflux condenser should be adjusted to a rate such that the methanol and methyl formate formed during the reaction distil out (Note 5). After all the acetal has been added, heating is continued for 1 hour (Note 6). The mixture is allowed to cool and is poured into 1 1. of IN sodium hydroxide. The resultant solution is extracted with chloroform in a liquid-liquid extractor for 24 hours. The chloroform is separated, dried over sodium sulfate, and removed by distillation through a short column on a steam bath. 

Note If the mobile phases contains formamide the chromatograms should be freed from it by heating to 130-140 °C in the drying cupboard for 1 h before applying the reagent [6]. 

The submitters purified technical-grade N,N-dimethyl-formamide by distillation from powdered calcium hydride. The checkers used N,N-dimethylformamide that had been dried... 

The acetylation of amylopectin with pyridine and acetic anhydride presents more difficulty, even when using freeze-dried material,26 and the most satisfactory method is that involving prior dispersion in formamide, after which esterification occurs readily at room temperature. 

B. Cydopropylbenzene. In a 1-1. three-necked flask equipped, with a stirrer and a thermometer extending into the flask but free from the stirrer are placed 500 ml. of redistilled dimethyl-formamide and zinc-copper couple prepared from 131 g. (2 g. atoms) of zinc (Note 8). The mixture is cooled to 7° in an ice bath, and 1,3-dibromo-l-phenylpropane is added to the stirred mixture at a rate sufficient to maintain the reaction temperature at 7-9° (Note 9). The mixture is stirred for 30 minutes after the addition is completed, poured into 1 1. of water, and then steam-distilled until the condensate is homogeneous or 11. of water has been collected. The organic layer is separated from the distillate, and the aqueous layer is extracted with three 100-ml. portions of ether. The combined organic portions are washed with four 50-ml. portions of water and dried over anhydrous potassium carbonate. The ether is removed by distillation at atmospheric pressure at water bath temperature. The residue is distilled to give 88-100 g. (75-85%) of cydopropylbenzene, b.p. 170-175° (Note 10), 26d 1.5306-1.5318. 

To a cooled mixture of 34 g 30% H202 and 150 g formic acid, add dropwise a solution of 32.4 g (0.2M) isosafrole in 120 ml acetone (keep temperature below 40°). Let stand about twelve hours and evaporate in vacuum. Add 60 ml methanol and 360 g 15% sulfuric acid to the residue and heat on water bath three hours. Cool, extract with ether or benzene and evaporate in vacuum the extract to give 20 g 3,4-methlenedioxybenzyl-methyl ketone (I) (can distill 115/2). Add 23 g (I) to 65 g formamide and heat at 190° for five hours. Cool, add 100 ml H202, extract with benzene and evaporate in vacuum the extract. Add 8 ml methanol and 57 ml 15% HCI to residue, heat on water bath two hours and evaporate in vacuum (or basify with KOH and extract the oil with benzene and dry, evaporate in vacuum) to get about 11 g MDA. In this, as in the other syntheses, either the cis or trans (alpha or beta) propenylbenzenes (or a mixture) may be used. 

M p-methoxy (or other group)-Br-benzene (see this paper for prepartion) and 4.6 g Mg. Rapidly add 18.5 g chloroacetone in 50 ml ether. Evaporate the ether by heating in oil bath and then at about 135° for one hour. Cool and add ice and dilute HCI extract the oil with ether and dry, evaporate in vacuum to get about 11 g product (can distill 106/18). 0,057 M of the ketone product in 16 g formamide in 100 ml round bottom flask, with an air condenser. Heat twelve hours at boiling and then reflux with 35 ml 30% NaOH eleven hours and separate the amine layer and dry, evaporate in vacuum to get the amphetamine. 

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