Imino ethyl ether

Imino compounds. These substances contain the -C=NH group and, because they are strong, unstable bases, they are kept as their more stable salts, such as the hydrochlorides. (The free base usually hydrolyses to the corresponding 0X0 compound and ammonia.) Like amine hydrochlorides, the salts are purified by solution in alcohol containing a few drops of hydrochloric acid. After treatment with charcoal, and filtering, dry ethyl ether (or petroleum ether if ethanol is used) is added until crystallisation sets in. The salts are dried and kept in a vacuum desiccator. 

We then directed/our attention to the properties of fluoro-methyl cyanide, as it seemed likely, on theoretical grounds, that it would undergo certain addition reactions very readily. Alcohol and dry hydrogen chloride readily converted it into Jluoroacetimino ethyl ether hydrochloride (VI), which was converted into the amidine (VII) by means of alcoholic ammonia. Similar condensation of the cyanide with 2-fluoroethanol and phenol yielded jluoroacetimino 2 jluoroethyl ether hydrochloride (VIII R = CHj CHjF) and the corresponding phenyl imino ether hydrochloride (VIII i2 = Ph) respectively. Analogous experi-... 

Stoichiometric experiments were conducted with the functionalized alkenes to further explore iron-substrate interactions and gauge relative coordination affinities. Several bis(imino)pyridine iron amine and ketone compounds were isolated and studied using a combination of X-ray diffraction, NMR and Mossbauer spectroscopy and established electronic structures similar to that for ( PDI)Fe(N2)2-In the absence of H2, diallyl ether and allyl ethyl ether underwent facile C-0 bond cleavage and yielded a near equimolar mixture of the corresponding iron allyl and alkoxide complexes [89]. Our group has recently published a comprehensive study on these types of reachons and discovered rare examples of C-0 bond cleavage in saturated esters [89]. 

The synthesis displays interesting stereochemical features. Thus, ethyl 2-(l -benzyloxycarbonylaminoethyl)-(J )-2-thiazoline-4-carboxylate (197) was obtained (0 by the imino-ether route , by condensing L-2-benzyloxy-carbonylaminopropioimino ethyl ether (198) and ethyl L-cysteinate hydrochloride (route A) and (ii) by the dehydration of benzyloxycarbonyl-L-alanyl-L-cysteine ethyl ester (199) (route B). Acidic hydrolysis of the... 

The low structural specificity in the local anesthetic sell cs is perhaps best illustrated by phenacalne (91), a local an-I -.lhetic that lacks not only the traditional ester or amide func-I ion but the basic aliphatic nitrogen as well. First prepared at I lie turn of the century, a more recent synthesis starts by con-ili iusation of p-ethoxyaniline with ethyl orthoacetate to afford I he imino ether (90), Reaction of that intermediate with a sec-I liil mole of the aniline results in a net displacement of ethanol, iiobably by an addition-elimination scheme. There is thus ob-I.lined the amidine, 91, phenacalne. 

Preparation of 2-Hydroxy-4,4 -Diamidinostilbene Dihydrochloride 10 grams of 2-hydroxy-4,4 -dicyanostilbene were suspended in 250 cc of absolute ethyl alcohol and the mixture saturated with dry hydrogen chloride at 0°C. The whole was left for eight days at room temperature. The imino-ether hydrochloride formed was filtered off, washed with dry ether and dried in the air for a short time. It was then added to 250 cc of 10% ethyl alcoholic ammonia and the whole heated for 5 hours at 45°C. The 2-hydroxy-4,4 -diamidino-stilbene dihydrochloride which separated was crystallized from 10% hydrochloric acid. It forms pale yellow needles, MP 357°C (decomposition). 

A solution of 100 g. of c. p. concentrated sulfuric acid in 700 cc. of water is prepared in a 5-I. flask, 1500 cc. of cracked ice added, and the mixture shaken until ice forms on the outside of the flask. After about half of this solution has been poured into the cold ether solution of the imino ether, using a funnel to remove the excess ice, the mixture is shaken for exactly fifteen seconds (Note 4), allowed to settle, and the layers separated. The remaining acid is added to the ether layer in two portions, the mixture each time being shaken for fifteen seconds, and separated. Since the ether solution, although now free of the imino ether, still contains a small amount of ethyl phenylaceto-acetate, it is saved to be combined with the main portion later. 

Ethyl a-phenylacetoacetate can be prepared by the hydrolysis of a-phenylacetoacetonitrile in absolute alcohol with dry hydrogen chloride.1 The present method differs in specifying neutralization of the hydrogen chloride with sodium carbonate and hydrolysis of the imino ether in aqueous sulfuric acid, so that the product separates as fast as it forms, thus being protected from further decomposition, with a considerably increased yield as the result. 

Imino ethers and, in particular, lactim ethers [141] such as O-ethylpyrrolidone 384a [142] or O-trimethylsilylcaprolactam 384b, which is formed, in equilibrium with N-trimethylsilylcaprolactam, on treatment of caprolactam with HMDS 2, condense readily with activated methylene compounds such as methyl or ethyl cyanoacetate to the y9-enamino esters 385 a and 385 b [140] whereas O-alkylureas such as 2-methoxyimidazoline 386 [143-146] afford products such as 387. 

It was to be expected that the imino ether hydrochlorides would be hydrolysed in the animal body to give the corresponding fluoroacetate and ammonium chloride, and the toxicities should be roughly the same as those of the fluoroacetates. The results show this to be the case. The compound (VIII iZ = CH2,CH2F) was expectedly more toxic than the other compounds, as this would be hydrolysed to 2-fluoroethyl fluoroacetate which is known to be twice as toxic as methyl or ethyl fluoroacetate,1 as indicated below. 

Reduction of a-imino ketones 52, prepared from 1,2-diketones 51 and 1 equiv of an amine, with sodium in ether, followed by treatment with ethyl chloroformate or... 

Phenylacetamide has been obtained by a wide variety of reactions from benzyl cyanide with water at 250-260° 6 from benzyl cyanide with water and cadmium oxide at 240° 6 from benzyl cyanide with sulfuric acid 7 8 by saturation of an acetone solution of benzyl cyanide with potassium hydrosulfide 9 from benzyl cyanide with sodium peroxide 10 by electrolytic reduction of benzyl cyanide in sodium hydroxide 11 from ethyl phenyl-acetate with alcoholic 12 or aqueous 13 ammonia from phenyl-acetic acid with ammonium acetate 14 or urea 15 from diazoacetophenone with ammoniacal silver solution 16 from phenyl-acetic acid imino ether hydrochloride and water 17 from acetophenone with ammonium poly sulfide at 215° 18 from benzoic acid 19 and by heating the ammonium salt of phenyl-acetic acid.20... 

A mixture of the crude oil of methyl 2-bromo-3- 4-[2-(5-ethyl-2-pyridyl)ethoxy]phenyl propionate (73.0 g) thiourea (14.2 g), sodium acetate (15.3 g) and ethanol (500 ml) was stirred for 3 hours under reflux. The reaction mixture was concentrated under reduced pressure, and the concentrate was neutralized with a saturated aqueous solution of sodium hydrogencarbonate, to which were added water (200 ml) and ether (100 ml). The whole mixture was stirred for 10 min to yield 5- 4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl -2-imino-4-thiazolidinone as crystals (0.3 g, 523.0%). Recrystallization from methanol gave colorless prisms, melting point 187°-188°C, dec. 

Cyclocondensation of the cyclic anhydride 212 and ethyl o-fluoroben-zoylacetate with the imino ether 213 gave l,3,4,6-tetrahydro[l,4]ox-azino[4,3-h]isoquinolin-6-one (214) (81JHC767) and [l,4]oxazino[4,3-a]quinoline-5-carboxylate (215) (80JHC1729), respectively. 

Common synthetic methods for the preparation of cyclic 8-enamino esters are the condensation between a lactim ether and benzyl cyanoacetate followed by hydrogenolytic decarboxylation, or the imino ester carbon-carbon condensation with tert-butyl cyanoacetate followed by a trifluoroacetic acid treatment. The use of a thiolactam condensed with ethyl bromoacetate gives, after sulfur extrusion by triphenylphosphine, cyclic 8-enamino esters. Compared with these methods, the Meldrum s acid condensation followed by the monodecarboxylating transesterification described here is more convenient and practical. An extension of this procedure permits preparation of smaller... 

Alkoxy-5(2i/)-oxazolones are available from ethyl cyanoformate via a simple albeit poor yielding route <89HCA825>. Imino esters (173), formed from the cyanoformate and an alcohol, are reacted with a ketone or aldehyde in the presence of BF3 etherate to give the oxazolone and a triazine triester (174) as the main product (Scheme 83). In a related synthesis, tosyloxyiminoacetates... 

A synthesis shown below of ethyl oxazole-4-carboxylate illustrates a sophisticated use of this strategy, in which an imino ether and the potassium enolate of an aldehyde are involved " iminoethers on reaction with aminoacetal give amidines, which close in acid to give 2-substituted imidazoles. " " The process can be conducted without isolation of the intermediate. 

Comforth et al have devised a flexible method of synthesizing oxazoles ( 9) from the condensation of an imino ether (88) and ethyl glycinate hydrochloride, followed by reaction with an alkyl formate and potassium alkoxide, and cyclization of the product in hot acetic acid. The reported yields in various stages are fairly good. 

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