Hydrates, alcoholates from isolation

Hammett equation, applied to azines, 217 Hetarynes, 121-143 contrasted with arynes, 125 Heteroaromatic compounds, covalent hydration of, 1-41 "pKa generalizations for, 48-61 Heterocyclic acids, pH-rate profile for, 67 Heterocyclic diazonium compounds, 241 Heptaazanaphthalenes, 393 Hexaazanaphthalenes, 393 Hippuroflavin, 80 Hydrated salts, isolation of, 16 Hydrates, alcoholates from, 16 isolation of, 16... 

Soulier et al. (35) isolate eight triterpenic alcohols from sal and illipe butters besides other compounds. They separate these compounds after saponification of the fatty matter and fractionation of the unsaponifiable on an aluminium oxide column (hydrated at 5%). Two successive HPLC separations and a TLC-AgN03 permit the isolation of highly purified fractions. Through the use, among others, of the H-NMR and MS techniques, they identify nine... 

H hydrogen bonding between water and exposed polyvinyl alcohol OH 0-H assigned as a one-to-one hydrogen bonded to an isolated OH in the manner as OH OH2 from the effect of the hydration of the isolated alcohol OH — this pertains to the interactions of water with the OH groups in poly(ethylene-co-vinyl alcohol) (EVOH) Water and polyvinyl alcohol OH... 

Terpin hydrate [2451-01-6] (10), one of the most weU-known expectorants, is isolated from cmde pine rosin left after the distillation of volatile terpene hydrocarbons and alcohols. It is also manufactured from turpentine (a-pinene) by acid-cataly2ed hydration. Terpin hydrate may exist as cis and trans isomers, but only the cis isomer forms a stable, crystalline monohydrate. Terpin hydrate is available in the United States only in prescription products. 

Interestingly, the product actually isolated from alkyne hydration is not the vinylic alcohol, or enol (ene + ol), but is instead a ketone. Although the enol is an intermediate in the reaction, it immediately rearranges to a ketone by a process called keto-enol tautomerisni. The individual keto and enol forms are said to be tautomers, a word used to describe constitutional isomers that interconvert rapidly. With few exceptions, the keto-enol tautomeric equilibrium lies on the side of the ketone enols are almost never isolated. We ll look more closely... 

Although this material contains a small amount of the symmetrical dihydrazide, which is not easily eliminated on crystallization, it is entirely satisfactory for use as a reagent for the isolation of ketones. A purer product, m. p. 192°, with decomposition, can be obtained by adding the solution prepared from ethyl chloroacetate and trimethylamine to an alcoholic solution containing a considerable excess of the hydrazine hydrate. 

There is the possibility that complexes isolated from aqueous (or aqueous alcoholic) media are not hydroxide adducts, but, instead, hydrated alco-holates. The above adaptation of the Karl Fischer analysis does not, unfortunately, distinguish between a hydroxide ion and a water molecule. Such a distinction could possibly be made by detailed x-ray analysis however, neither alcoholates nor adducts have, as yet, been obtained in a form suitable for such a study. 

A solution of 2-fluoro-4-methoxyacetophenone (11.3 mmol) dissolved in 20 ml ethyl alcohol was treated with 1.4 ml hydrazine hydrate and then refluxed 6 hours. This mixture was concentrated and the residue treated with 10 ml ethylene glycol. This mixture was heated 18 hours at 150°C, then cooled, and diluted with 50 ml water. It was then extracted three times with 60 ml CH2C12, washed with 10 ml brine, dried with MgS04, and concentrated. The residue was recrystallized from EtOAc and the product isolated in 59% yield. 

The Step 2 product (0.40 mmol) suspended in methyl alcohol/water, 10 1, was treated with p-toluenesulfonic acid hydrate (0.04 mmol), then stirred 18 hours at ambient temperature, and then diluted with EtOAc. The organic solution was washed twice with saturated NaHC03 solution, once with brine, dried using Na2S04, filtered, and concentrated. The residue was recrystallized from EtOAc and heptane and the solid washed with heptane/CH2Cl2, 1 1. The solid was dried in vacuo at 60 C and the product isolated in 70% yield as a white solid. The product shrinks at 90.8°C, mp= 115-117°C. 

The product from Step 5 (20.7 g) and 8.6 ml 85% hydrazine hydrate were dissolved in 300 ml ethyl alcohol, refluxed 3 hours, cooled, diluted with 400 ml water, acidified with 37% HCl, and stirred 30 minutes. The product was isolated as a precipitated in 96% yield, mp = 200-202 °C. 

To 18 ml DMSO was added l-(3-aminopropyl)-2-pyrrolidinone (6.7 mmol), the product from Step 3 (4.79 mmol), l-[3-dimethylamino)-propyl]-3-ethylcarbodiimide hydrochloride (5.99 mmol) and 1-hydroxyIbenzotriazole hydrate (7.2 mmol), and the reaction stirred overnight at ambient temperature. The crude products were diluted with EtOAc, rinsed with saturated NH4CI solution, and washed twice with water. The organic layer was dried, concentrated, purified by chromatography on silica gel using CH2Cl2/methyl alcohol, 9 1, and the product isolated in 95% yield. 

In a separate vessel, hydrazine hydrate (45 mmol) at 0°C was added to the product from Step 1 (45 mmol) dissolved in 45 ml ethyl alcohol, and the suspension stirred at ambient temperature 10 minutes. The intermediate of this Step was added to this mixture and heated to 70 °C 4 hours. The mixture was filtered, concentrated, the residue partitioned between CH2CI2 and water, and re-concentrated. It was dissolved in 60 ml 1,2-dichloroethane, 7.5 ml phosphorus oxychloride added, and refluxed 2 hours. The contents were diluted with CH2CI2, neutralized with solid Na2C03 and NaHCOj, dried, and concentrated. The product was purified by chromatography using CH2Cl2/methyl alcohol, 95 5, crystallized in EtOAc, and isolated in 28% yield. H-NMR data supplied. 

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