2- -pyridines, dehydrative

It has generally been assumed that phosphorous oxychloride-pyridine dehydrations, the elimination of sulfonates, and other base catalyzed eliminations (see below) proceed by an E2 mechanism (see e.g. ref. 214, 215, 216). Concerted base catalyzed eliminations in acyclic systems follow the Saytzelf orientation rule i.e., proceed toward the most substituted carbon), as do eliminations (see ref 214). However, the best geometrical arrangement of the four centers involved in 2 eliminations is anti-coplanar and in the cyclohexane system only the tran -diaxial situation provides this. 

When, in the phosphorous oxychloride-pyridine dehydration of an alcohol these rules conflict, the stereoelectronic factor determines the direction of elimination ... 

Materials Required Chlorthalidone 0.3 g pyridine (dehydrated) 50 ml 0.1N tetrabutylammonium hydroxide. 

Phosphoryl chloride-Pyridine dehydration of alcohols [1, 878-879, at end]. Although thebaine (1) can be considered as the methyl enol ether of codeinone (2), no direct synthesis has been achieved. Rapoport123 has recently carried out a convenient indirect synthesis of (1) from Ae-dihydrothebaine (3). Addition of methyl hypobromite (generated from NBA in methanol) gave (4) in 62% yield, and this... 

The lactone (31), obtainable in three steps from cholanic acid, served as the starting point in a different approach. Phosphorus oxychloride-pyridine dehydration of the corresponding hydroxy-methyl ester afforded a complex mixture of unsaturated esters in which the cis and trans non-conjugated esters (32) predominated Hydrolysis of the entire mixture and treatment of the mixture of free acids with iV-bromosuccinimide gave the new buf-20(22)-enolide (33). DDQ dehydrogenation of (33) could be controlled to yield either the desired bufa-... 

Scheme 4 Compound (45) prepared from a-santonin (41), on reduction afforded alcohol (46), which was converted to derivative (48) by standard organic reaction. Irradiation of (48) in benzene at room temperature followed by reflux in tetrahydrofuran and 2-propanol, produced 15-oxime derivative (49). Its conversion to nitrile (50) was achieved by treatmente with acetic anhydryde in pyridine. Dehydration of (50) followed by decyanation, yielded compound (52). Its acetonide derivative (53), was converted to compound (54), whose convertsion to rishitin (40), was achieved by heating with 0.5% PPA in ethanol...

CrOs-pyridine-methylene chloride. The oxidation of 3a,5a-cyclocholest-7-ene-6-ol (1) to the ketone (2) is unsatisfactory with either manganese dioxide (no reaction below 40°) or CrOs in pyridine (dehydration to the A > >-dicne). 

Dehydration of Alcohols. Various tertiary, secondary, and primary alcohols are dehydrated with Cu(OTf)2 to alkenes. Preferred formation of Zaitsev orientation products and ( )-alkenes are indicative of a carbocationic mechanism. Zn(OTf)2 and Mg(OTf)2 are ineffective. In selected exanqiles, yields are superior to those of H2SO4 and POCb/pyridine dehydrations. ... 

Phosphorus oxide chloride phosphoric acid pyridine Dehydration of alcohols s. U, 939... 

Perchloric acid Acetic acid, acetic anhydride, alcohols, antimony compounds, azo pigments, bismuth and its alloys, methanol, carbonaceous materials, carbon tetrachloride, cellulose, dehydrating agents, diethyl ether, glycols and glycolethers, HCl, HI, hypophosphites, ketones, nitric acid, pyridine, steel, sulfoxides, sulfuric acid... 

I60C-Hydroxy Derivatives of Gorticoids and their Acetonides. The preparation of 16a-hydroxy-9a-fluoroprednisolone (48) from the 3,20-bisethylene ketal of hydrocortisone acetate (49) has been reported (73). The latter was dehydrated with thionyl chloride in pyridine to yield the 4,9(11),16-triene (50). The 16,17-unsaturated linkage was selectively hydroxylated with OsO /pyridine to yield the 16a,17a-diol (51), which was converted... 

Reaction with Ammonia. Although the Hquid-phase reaction of acrolein with ammonia produces polymers of Htde interest, the vapor-phase reaction, in the presence of a dehydration catalyst, produces high yields of [ -picoline [108-99-6] and pyridine [110-86-4] n.2L mXio of approximately 2/1. 

Bisa.codyl, 4,4 -(2-PyridyLmethylene)bisphenol diacetate [603-50-9] (Dulcolax) (9) is a white to off-white crystalline powder ia which particles of 50 p.m dia predominate. It is very soluble ia water, freely soluble ia chloroform and alcohol, soluble ia methanol and ben2ene, and slightly soluble ia diethyl ether. Bisacodyl may be prepared from 2-pyridine-carboxaldehyde by condensation with phenol and the aid of a dehydrant such as sulfuric acid. The resulting 4,4 -(pyridyLmethylene)diphenol is esterified by treatment with acetic anhydride and anhydrous sodium acetate. Crystallisation is from ethanol. 

Medroxyprogesterone acetate (74) is stmcturaHy related to and has been prepared from hydroxyprogesterone (39) (Fig. 10). Formation of the bis-ketal accomplishes the protection of the ketones and the required migration of the double bond. Epoxidation with peracetic acid produces a mixture of epoxides (75), with a predominating. Treatment of the a-epoxide with methyl magnesium bromide results in diaxial opening of the epoxide. Deprotection of the ketones provides (76), which is dehydrated to (77) by treatment with dilute sodium hydroxide in pyridine. Upon treatment with gaseous hydrochloric... 

The reactions of primary amines and maleic anhydride yield amic acids that can be dehydrated to imides, polyimides (qv), or isoimides depending on the reaction conditions (35—37). However, these products require multistep processes. Pathways with favorable economics are difficult to achieve. Amines and pyridines decompose maleic anhydride, often ia a violent reaction. Carbon dioxide [124-38-9] is a typical end product for this exothermic reaction (38). 

Oxa2oles react with dienophiles to give pyridines after dehydration or other aromatization reactions (69,70). A commercially important example is the reaction of a 5-aLkoxy-4-methyloxa2ole with 1,4-butenediol to yield pyridoxine (55), which is vitamin... 

These reactions can be cataly2ed by bases, eg, pyridine, or by Lewis acids, eg, 2inc chloride. In the case of asymmetric alcohols, steric control, ie, inversion, racemi2ation, or retention of configuration at the reaction site, can be achieved by the choice of reaction conditions (173,174). Some alcohols dehydrate to olefins when treated with thionyl chloride and pyridine. 

Thus, Mathis et al. [1, 2] investigated oxidation reactions with 4-nitroperbenzoic acid, sodium hypobromite, osmium tetroxide and ruthenium tetroxide. Hamann et al. [3] employed phosphorus oxychloride in pyridine for dehydration. However, this method is accompanied by the disadvantages that the volume applied is increased because reagent has been added and that water is sometimes produced in the reaction and has to be removed before the chromatographic separation. 

If homolytic reaction conditions (heat and nonpolar solvents) can be avoided and if the reaction is conducted in the presence of a weak base, lead tetraacetate is an efficient oxidant for the conversion of primary and secondary alcohols to aldehydes and ketones. The yield of product is in many cases better than that obtained by oxidation with chromium trioxide. The reaction in pyridine is moderately slow the intial red pyridine complex turns to a yellow solution as the reaction progresses, the color change thus serving as an indicator. The method is surprisingly mild and free of side reactions. Thus 17a-ethinyl-17jS-hydroxy steroids are not attacked and 5a-hydroxy-3-ket-ones are not dehydrated. 

One of the most widely used systems for dehydration is the combination of phosphorous oxychloride and pyridine. This reagent is apparently incompatible with the A" -3-keto system/ probably due to formation of a phosphorylated enol. It is, however, more selective than thionyl chloride-pyridine since 17a-alcohols are not dehydrated ... 

A iD-Corticoids have been important intermediates since it was shown ° that substitution at C-9 enhances anti-inflammatory activity. These olefins are usually obtained from 11a- or 11)5-alcohols, and consequently several refined methods have been devised for effecting this dehydration. It is desirable that such methods be compatible with the presence of A" -3-ketone and 17-hydroxy functions. The first direct procedure for which high yields were claimed was described in a patent issued to Upjohn. According to this method, the alcohol (11a or )5) is treated first with A-bromoacetamide in pyridine, then with sulfur dioxide. Recently it has been claimed " that the A-haloamide/sulfur dioxide method gives results superior to other methods, although the methanesulfonyl chloride/sulfur dioxide procedure (see below) apparently was not compared (see also ref. 94). 

Methylchlorosulfite has been used to dehydrate lljS-alcohols ° the best conditions use THF-pyridine at low temperatures. By-products include 11 )5-methylsulfite and A -olefin. ° ... 

Thionyl chloride behaves in some circumstances as though it dehydrates by tran -diaxial elimination, as described for phosphorous oxychloride. For example, the 5a-alcohol (102) undergoes anti-Saytzelf elimination to give the A" -olefin. In this particular example, phosphorous oxychloride-pyridine does not work, and acetic anhydride-sulfuric acid gives the A -isomer (ref. 185, p. 199). 

Acetonides are quite stable to base, and to oxidation, dehydration and acylation reactions carried out in pyridine. They are cleaved by acid hydrolysis. The 17,21-acetonides of 17a,21-dihydroxy-20-keto steroids and related acetals are split by very mild acid conditions. ... 

The reaction can be carried out in any inert solvent, but using a base such as pyridine has an additional advantage in the subsequent dehydration step... 

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