Nitro ethyl toluenes

A mixture of 17.6 grams of p-n-butoxyacetophenone, 12.1 grams of piperidine hydrochloride, 4.5 grams paraformaldehyde, 0.25 cc concentrated hydrochloric acid, 52.5 cc nitro-ethane, 7.5 cc of 95% ethanol, and 15 cc of toluene was boiled under reflux for one hour, removing water formed in the reaction by means of a condensate trap. The mixture was then cooled. The crystals which formed were collected by filtration, washed with anhydrous ether and recrystallized from methyl ethyl ketone. The crystals thus obtained, which melted at 174°-175°C, were shown by analysis to be 4-n-butoxy-beta-piperidinopropiophen-one hydrochloride. 

Relative rates of alkylation of toluene and benzene using a mixture of nitro-sonium hexafluorophosphate, nitromethane (or acetonitrile) and aliphatic amine as the alkylations agent have been determined at 25 °C as follows360 1.5 (ethyl-amine), 2.5 (i-propylamine) and 3.5 (benzylamine) nothing more as yet is known about the kinetics of alkylation with these new alkylating reagents. 

Filter, wash toluene with water, NaHC03, water and dry, evaporate in vacuum to get 100 g gamma-Cl-butyraldehyde (I) (can distill 28/2). 10 g (I), 20 g 3-nitro-phenylhydrazine dissolve in the minimum volume of hot ethanol containing 10% glacial acetic acid. Heat on steam bath one hour cool and add water until dark oil separates. Evaporate in vacuum the ethanol and decant the water to get the oily gamma-Cl-butyraldehyde-3-intro-phenylhydrazone(II). 29 g (11), 300 ml concentrated HC1, ZOO ml benzene stir three hours, replace benzene with fresh benzene and stir four hours. Combine the two benzene portions, wash with water and dry, evaporate in vacuum to get 4 g 3-(beta-Cl-ethyl)-4 and 6-nitroindole (m). 3.56 g (III), 200 ml ethanol, 200 ml 34% aqueous DMA (or other amine) and let stand at room temperature for one week. Evaporate in vacuum the ethanol, filter, dissolve the precipitate in dilute HC1 and filter. Basify the filtrate with dilute NaOH to precipitate 3 g 4 and 6-nitro-DMT (IV). 5.2 g (IV), 350 ml ethanol, 100 ml IN NaOH heat to 50° and add a solution of 3 g Na dithionite in 15 ml 0.2N NaOH. filter hot and evaporate in vacuum to get 2 g 4 and 6 amino-DMT (can purity by dissolving in HC1, filter, basify, extract with ether and dry and evaporate in vacuum the extract). 

To 23 g Na in 350 ml ethanol add 146 g ethyl-oxalate and 171 g 2-nitro-6-CI-toluene and reflux forty minutes. Dilute the red solution with water and steam distill until no more starting material is distilled. The aqueous residue is filtered, acidified with HC1 and filtered to get 102 g 2-nitro-6-CI-phenylpyruvic acid (I) (recrystallize-benzene). Add 81 g (I) in dilute NH4OH to a solution of 560 g FeS04.7H20 and 230 ml concentrated NH4OH and 2 L water and boil five minutes. Filter, wash precipitate with dilute NH4OH, water and acidify filtrate with dilute HCI to get 60 g 4-CI-2-indole-COOH (11) (recrystallize-aqueous ethanol). 9.78 g (II) and 6.7 g CuCN in 35 g quinoline and reflux (about 237°) for twenty hours. Pour the hot solution into a mixture of 25 ml concentrated HCI and ice. Stir and filter wash precipitate with water and extract the filtrate and precipitate three times with ether. Wash the ether with HCI, water and dry, evaporate in vacuum to get 3.6 g 4-CN-indole (recrystallize-water). Or, heat (II) alone at 290° until fusion then heat at 250° for ten minutes until C02 evolution ceases to get 4-CN-indole. For conversion to 4-formyl-indole see HC A 51,1616(1968). 

Amines. The common impurities found in amines are nitro compounds (if prepared by reduction), the corresponding halides (if prepared from them) and the corresponding carbamate s ts. Amines are dissolved in aqueous acid, the pH of the solution being at least three units below the pK value of the base to ensure almost complete formation of the cation. They are extracted with ethyl ether to remove neutral impurities and to decompose the carbamate salts. The solution is then made strongly alkaline and the amines that separate are extracted into a suitable solvent (ether or toluene) or steam distilled. The latter process removes coloured impurities. Note that chloroform cannot be used as a solvent for primary amines because, in the presence of alkali, poisonous carbylamines are formed. However, chloroform is a useful solvent for the extraction of heterocyclic bases. In this case it has the added advantage that while the extract is being freed from the chloroform most of the moisture is removed with the solvent. 

Cyclization of 2-[(3-acetamido-2-pyridyl)amino]benzoic acid (202) in 0.5 N sulfuric acid gave 6-amino-ll//-pyrido[2,l-h]quinazolin-ll-one (203) (84MI3). 2-[(6-Methyl-, 5-nitro-, and 3-nitro-2-pyridyl)amino]benzoic acids were cyclized into 9-methyl, 8-nitro, and 6-nitro-l 1 //-pyrido[2,l -ujquina-zolin-ll-ones, respectively, by the action of 80% sulfuric acid. Ethyl 2-(2-pyridylamino)benzoate, prepared in the reaction of 2-chloropyridine and ethyl anthranilate in boiling toluene for 10 h, afforded ll//-pyrido[2,l-b]-quinazolin-ll-one (27) on heating at 200-210°C for 0.5 h (92MI2). 

A mixture of 4-nitro-2-n-butoxybenzoic acid, anhydrous potassium carbonate and 400 ml of dry toluene was refluxed and stirred under a continuous water separator. When the evolution of water had ceased (3 h), the water separator was removed and there was added diethylaminoethyl chloride. The mixture was then refluxed with stirring for about 20 h, filtered while hot, and the solvent was removed from the filtrate by distilling in vacuo. The residual oil was dissolved in dilute hydrochloric acid, the solution was decolorized with activated carbon and the base was liberated by the addition of excess ammonia. The base was extracted with ethyl acetate, the solution was dried, and the ethyl acetate was removed by distilling in vacuo, yielding 2-diethylaminoethyl 4-nitro-2-n-butoxybenzoate as a pale yellow oil. 

Gomberg and Pemert4 recommended the use of the sodium diazotates for the preparation of biaryls from aniline and from p-toluidine and the normal diazo method for negatively substituted amines such as the bromo- and nitro-anilines. Grieve and Hey 7 found little difference in the yields of biaryls obtained by the two procedures when they coupled diazotized aniline with six different components benzene, toluene, m-xylene, chlorobenzene, nitrobenzene, and ethyl benzoate. Where it is applicable, this modification offers the advantage that the dropwise addition of alkali is eliminated. 

Manufacturer Base Nitro cellulose Nitro glycerin Dinitro toluene Diphenyl amine Ethyl centralite Dibutyl phthalate... 

Note 8. The yield of product in rims on this scale is 83-87%. This preparation also has been carried out more than 20 times on twice the scale described with the same range of yields. Concentrating the filtrates and washings gives highly colored material that is impractical to purity. The tan product of this preparation is quite pure, but can be recrystallized from toluene, ethyl acetate, or methyl ethyl ketone with charcoal to give light yellow material. Product contaminated with the somewhat more soluble 8-nitro isomer suffers considerable loss if complete removal of this impurity is attempted. 

Higher-molecular-weight amines are treated in the liquid phase usually in solvents like ethyl acetate, toluene, chlorobenzene, or chloro-naphthalene. This process is illustrated by the preparation of p-nitro-phenyl isocyanate (95%). Amine hydrochlorides or carbamic acids are sometimes used in place of the free amine. ... 

Recently the nitro-group has been introduced directly into the side-chain.1 If, e.g., toluene or ethyl benzene be heated with weak nitric acid (sp. gr. 1.076) in a bomb up to about xoo°, phenylnitromethane, C8Hj.CH2.N02, or phenylnitroethane, C H,.CH.N02.CH3 is obtained. 

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