Phosphorus oxychloride, dehydration alcohols using

In synthetic practice, it is more common to dehydrate alcohols using thionyl chloride or phosphorus oxychloride in pyridine. Generally, the mechanism involved in such reactions is the formation of chlorosulhnyl or dichlorophosphoryl esters, followed by El or E2 elimination ... 

Alcohols can be dehydrated by a number of procedures. One method is to use a dehydrating agent such as phosphorus oxychloride (POCI3), and another method is acid-catalyzed dehydration using sulfuric acid (H2SO ) or phosphoric acid (HjPO ). An example of acid-catalyzed dehydration is in Figure 3-17, and the mechanism is shown in Figure 3-18. 

In preparation for the eventual removal of the undesired oxygen function at C-10 of 313 via a Birch reduction, the phenol 313 was phosphorylated with diethyl phosphorochloridate in the presence of triethylamine to give 314, which underwent stereoselective reduction with sodium borohydride with concomitant N-deacylation to deliver the amino alcohol 315. N-Methylation of 315 by the Eschweiler-Clarke protocol using formaldehyde and formic acid followed by ammonolysis of the ester group and acetylation of the C-2 hydroxyl function afforded 316. Dehydration of the amide moiety in 316 with phosphorus oxychloride and subsequent reaction of the resulting amino nitrile 317 with LiAlH4 furnished 318, which underwent reduction with sodium in liquid ammonia to provide unnatural (+)-galanthamine. 

The El reaction is not ideal for the dehydration of primary or secondary alcohols since vigorous heating is needed to force the reaction and this can result in rearrangement reactions. In alternative methods which are useful, reagents like phosphorus oxychloride (POCl3) dehydrate secondary and tertiary alcohols under mild basic conditions using pyridine as solvent (Following fig.). The phosphorus oxychloride serves to activate the alcohol,... 

Figure 1.11 shows the second example. Triterpene alcohol 14 with an axial hydroxy group can be dehydrated smoothly by treatment with phosphorus oxychloride in pyridine to give 16 through conventional E2 elimination mechanism. However, dehydration of the equatorial alcohol 15 leads to a rearrangement product 17 through the mechanism as shown in Figure 1.11. This type of simple stereochemical knowledge is very useful in synthetic planning.

The relatively harsh conditions (acid and heat) required for alcohol dehydration and the structural changes resulting from carbocation rearrangements may result in low yields of the desired alkene. Dehydration, however, can be carried out under milder conditions by using phosphorus oxychloride (POCI3) and pyridine. 

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