Carbinol dehydration

Pyrazole, N-vinyl-polymerization, 5, 269 3H-Pyrazole, 3,3,5-trimethyl-irradiation, 5, 251 Pyrazole carbaldehydes reactions, 5, 260 Pyrazole carbinols dehydration, 5, 261... 

Another example is tamoxifen (89). Its synthesis begins with Grignard addition of reagent to aryl ketone giving carbinol Dehydration leads to the readily separable and... 

A detailed study of the synthesis of thiadiazole ketones via the reaction of 3-chlorocarbonyl-l,2,5-thiadiazoles with dialkylcadmium reagents was reported. In each case the ketone was obtained in only low yield, the major product being a tertiary carbinol or a tertiary carbinol dehydration product. These products stemmed from the reaction of the desired ketone with a second equivalent of the cadmium reagent. Thus, the 1,2,5-thiadiazole ketones are among the very few... 

Aside from the above-mentioned synthesis the best proof of the structure of stylopine is that of Spath and Posega (241), who reduced protopine to the carbinol, dehydrated this to the quaternary chloride, and then following Perkin s procedure eliminated methyl chloride by distillation in a high vacuum. The resulting product (LI) was identical with dl-tetrahydro-... 

Isobutyl alcohol, isobutanol, 2-methyl-propanol, isopropyl carbinol, Me2CHCH20H. B.p. 108°C. Occurs in fusel-oil. Oxidized by potassium permanganate to 2-methyl-propanoic acid dehydrated by strong sulphuric acid to 2-methylpropene. 

Primary amines undergo nucleo philic addition to the carbonyl group of aldehydes and ketones to form carbinol amines These carbinolamines dehydrate under the conditions of their formation to give N substituted imines Secondary amines yield enamines... 

Toluene reacts with carbon monoxide and butene-1 under pressure in the presence of hydrogen fluoride and boron trifluoride to give 4-methyl-j iYbutyrophenone which is reduced to the carbinol and dehydrated to the olefin. The latter is cycHzed and dehydrogenated over a special alumina-supported catalyst to give pure 2,6- dim ethyl n aph th a1 en e, free from isomers. It is also possible to isomerize various dim ethyl n aph th a1 en es to the... 

Anhydrous stannous chloride, a water-soluble white soHd, is the most economical source of stannous tin and is especially important in redox and plating reactions. Preparation of the anhydrous salt may be by direct reaction of chlorine and molten tin, heating tin in hydrogen chloride gas, or reducing stannic chloride solution with tin metal, followed by dehydration. It is soluble in a number of organic solvents (g/100 g solvent at 23°C) acetone 42.7, ethyl alcohol 54.4, methyl isobutyl carbinol 10.45, isopropyl alcohol 9.61, methyl ethyl ketone 9.43 isoamyl acetate 3.76, diethyl ether 0.49, and mineral spirits 0.03 it is insoluble in petroleum naphtha and xylene (2). 

The reaction mixture is then transferred to a 2-I. round-bottom flask with wide neck, and to this is added all at once 300 g. of cracked ice, and the mixture is rapidly agitated by a rotary motion until the decomposition is complete (Note 7). Sufficient 30 per cent sulfuric acid is added to dissolve the magnesium hydroxide, and the mixture is then steam-distilled until oil no longer collects on the surface of the distillate. The distillate, which amounts to 1500-2500 cc., is saturated with sodium chloride and the upper layer separated. The aqueous layer is extracted with two loo-cc. portions of ether and the ether extract added to the alcohol layer. The ether solution is dried over anhydrous potassium carbonate, filtered, and heated carefully on the steam cone until all the ether is distilled. The crude alcohol is warmed one-half hour with about 5 g. of freshly dehydrated lime (Note 8). After filtering again and washing the lime with a little ether, the ether is distilled and the alcohol is distilled in vacuo from a Claisen flask (Note g). The carbinol distils at 88-93 /18 mm. (practically all distilling at 91°). The yield is 70-74 g. (61-65 P r cent of the theoretical amount) (Note 10). 

This heating prior to distillation obviates the necessity of intermediate isolation of the carbinol. The dehydration is evidenced by small explosions when the water drops on the hot reaction mixture. 

The stereochemistry of the product resulting from the reaction of a 17-keto steroid with ethylidenetriphenylphosphorane is different from that of the 17-ethylidene steroids obtained by dehydration of 17a-ethyl-17/ -hydroxy compounds, Wolff-Kishner reduction of A -20-keto steroids or by sodium-alcohol or sodium-ammonia " reductions of 17-ethynyl carbinols. These latter products have generally been assumed to possess the trans configuration (C-21 methyl away from the bulk of the ring system) because of anticipated greater stability. The cis configuration for... 

While the reductive procedure appears simpler, it also provides a higher proportion of the A -double bond isomer on dehydration than is obtained from the tertiary carbinol. This may be a consequence of the lower steric requirements of a A -olefin having only one alkyl group attached to C-20. In either case, all other double bonds must be protected before the ozonolysis and other free hydroxyls should be esterified prior to dehydration at C-20. 

In Sarett s total synthesis of cortisone, mild acid conditions were developed for the hydration of an ethoxyacetylenic carbinol to the ester without complete dehydration of the tertiary hydroxyl group. An acid-sensitive ketal group in another part of the molecule was also maintained. 

Reaction of the Mannich product (112) from acetophenone itself with the Grignard reagent from p-chlorobcnzyl chloride gives the carbinol, 113. Dehydration in this case gives the antihistamine pyrrobutamine (114). It is not immediately clear why dehydration does not occur in the other sense so as to afford the energetically more favored stilbene. 

Ullmann condensation of the sodium salt of p-chlorothiophe-nol (31) with 2-iodobenzoic (32) acid gives 33. Cyclization by means of sulfuric acid affords the thioxanthone, 34. Reaction with the Grignard reagent from 3-dimethylaminopropyl chloride affords the tertiary carbinol (35). Dehydration by means of acetic anhydride affords chlorprothixene as a mixture of geometric isomers, 36. (Subsequent work showed the Z isomer-chlorine and amine on the same side—to be the more potent compound.) Chlorprothixene is said to cause less sedation than the phenothiazines. ... 

Nitromifene (85) is such an agent. A Grignard reaction of aryl ether and ketone leads to tertiary carbinol Tosic acid dehydration leads to a mixture of 1 and stilbenes which constitute the antiestrogen, nitromi fene (85)... 

The search for opioid analgesics which show reduced addiction liability ha.s centered largely on benzomorphan and morphinan derivatives. Some research has, however, been devoted to derivatives of the structurally simpler meperidine series. The preparation of one such compound, picenadol (59), starts with the reaction of N-methyl-4-piperidone with the lithium derivative from m-methoxybromobenzene. Dehydration of the first formed carbinol 51 gives the intermediate 52. Deprotonation by means of butyl lithium gives an anion which can be depicted in the ambident form 53. In the event, treatment of the anion with propyl bromide gives the product 54 from reaction of the benzylic anion. Treatment of that product, which now contains an eneamine function. 

The finding that the anthelmintic thiazoloimidazole levamisole showed immunoregulatory activity spurred further investigation of this heterocyclic system. Synthesis of a highly modified analogue starts by displacement of bromine in keto ester 149 by sulfur in substituted benzimidazole 148. Cyclization of the product (150), leads initially to the carbinol 151. Removal of the ester group by saponification in base followed by acid-catalyzed dehydration of the carbinol affords the immune regulator tilomisole (152) [28]. 

The starting material can be prepared in known manner from dibenzo[a,d] cyclohepta-1,4-diene-5-one by a Grignard reaction with 3-dimethylaminopropyl magnesium chloride, hydrolysis and dehydration of the resulting carbinol. 

B) Preparation of Diphenyl-(N-Methyl-4-Plperidylidene)Methane The carbinol can be dehydrated with 60% sulfuric acid. In general, to one part of the carbinol there is added... 

There is no doubt that the carbinol equilibrium (Scheme 3-15) is comparable to the nitrous acid protonation-dehydration equilibrium (Scheme 3-8) if one disregards the nitrosoacidium ion intermediate. 

Inclusion of an acetylenic linkage as part of the side chain is apparently consistent with antidepressant activity. Reaction of propargyl magnesium bromide with dibenzocycloheptadieneone leads to carbinol 82. A Mannich reaction with formaldehyde and dimethylamine leads to 83 which, upon dehydration... 

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