Phosphorus oxychloride, alcohol dehydration with

Phosphine(s), chirality of, 314 Phosphite, DNA synthesis and, 1115 oxidation of, 1116 Phospholipid, 1066-1067 classification of, 1066 Phosphopantetheine, coenzyme A from. 817 structure of, 1127 Phosphoramidite, DNA synthesis and, 1115 Phosphoranc, 720 Phosphoric acid, pKa of, 51 Phosphoric acid anhydride, 1127 Phosphorus, hybridization of, 20 Phosphorus oxychloride, alcohol dehydration with. 620-622 Phosphorus tribromide, reaction with alcohols. 344. 618 Photochemical reaction, 1181 Photolithography, 505-506 resists for, 505-506 Photon, 419 energy- of. 420 Photosynthesis, 973-974 Phthalic acid, structure of, 753 Phthalimide, Gabriel amine synthesis and, 929... 

Tetrahydrostrychnine, CgjHggOgNg. HgO. This substance, also formed by the electrolytic reduction of strychnine, crystallises from alcohol in prisms, m.p. 202°, gives colour reactions of the strychnidine type, and yields both neutral and acid salts the hydrochloride, B. HCl, occurs in small needles readily soluble in water and the dihydriodide, B. 2HI. 2HjO, in pyramidal crystals. The base yields an amorphous nitrosoamine, the hydrochloride of which crystallises from warm water in lustrous, yellowish prisms. It also furnishes a crystalline monoacetyl derivative, and on heating with hydrochloric acid or phosphorus oxychloride is dehydrated to strychnidine. 

Phosphorus oxychloride, POCI3 Reacts with secondary and tertiary and alcohols to yield alkene dehydration products (Section 17.6). 

The requisite starting cyanohydrin is readily prepared from a 20-keto-pregnane substitution at C-21 has no effect on the success of this step. However, the stability of the cyanohydrin is markedly dependent on other features of the molecule thus a 3-acetate confers greater stability than the free alcohol, and a 3-ketone is so unstable that subsequent dehydration with phosphorus oxychloride gives poor yields of the A -unsaturated nitrile. 

Tnfluoromethyl homoallyl alcohols also dehydrate easily with phosphorus oxychloride-pyridine complex, but it is very difficult to remove water from their saturated analogues by the same method [82] (equation 52)... 

Pyrrolizidine amino-alcohols are readily dehydrated for example, hydroxyheliotridane and retronecanol, when treated with sulfuric acid, afford heliotridene (see e.g., refs. 105 to 107). A more complicated dehydration reaction is the transformation of the alkaloid rosmarinine into the alkaloid senecionine.83 Dehydration of 1-hydroxy-l-carbethoxypyrrolizidine53 in the presence of phosphorus oxychloride in pyridine results mainly in the formation of the A1,8-unsaturated ester (see Section II, E). The authors61,62 claimed that the dehydration product of l-carbethoxy-2-hydroxy-3-oxopyrrolizidine contained a A1,2-double bond (159). Later, however, the UV, IR, and NMR spectra67 revealed that the double bond had migrated the... 

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. 

Successive reduction of l,3-dimethyl-4,5,6,7-tetrahydrobenzo[c]-thiophen-4-one (Section III,C) with sodium borohydride and dehydration of the resulting alcohol with polyphosphoric acid gives the unstable 1,3-dimethyl derivative [(18) R = H] in excellent yield,35 and successive treatment of the same ketone with methylmagnesium iodide and acid gives the 1,3,7-trimethyl derivative [(18) R=Me] (Table IV) and a second compound which is reported to be a dimer. 36 When l,3-dimethyl-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one is treated with a mixture of phosphorus oxychloride and dimethyl-formamide (Vilsmeier-Haack formylation), it gives compound 19, which yields 20 on being treated successively with thioglycolic acid... 

The THP derivatives (130 X = H, Cl) have been deprotected and the resulting alcohols (131) oxidized with PCC yielding the chiral heterocycles (132) <92JOC1930>. Dehydration of a 1 1 mixture of the diastereoisomers (133) with phosphorus oxychloride gives the thiopyrano[4,3-c]thiopyran derivative (134) (48% yield) <84J0C5136>. 

From a careful study of vetiver oil (from the Moosanagar area of North India) Ganguly et al. ° have isolated and identified the two biogenetically important alcohols, (+)-allokhusiol (153) and (—)-khusiol (154). These two compounds co-occur with (-l-)-zizaene (155) and (+)-prezizaene (156), and furthermore it has been shown that (153) gives both (+)-zizaene (155) and (+)-prezizaene (156) on dehydration with phosphorus oxychloride, while treatment of khusiol tosylate with pyridine produces (+)-prezizaene as a minor product. It would also appear from these results that (-)-khusiol is enantiomeric with (-H)-allocedrol isolated by Tomita and Hirose but that (+)-allokhusiol is not the enantiomer of the alcohol identified by Carroll et al. ... 

Dehydration of secondary and tertiary alcohols with phosphorus oxychloride (POCI3) in pyridine leads directly to alkenes without isolating the dichlorophosphate intermediate. ... 

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.

Michael addition of methyl vinyl ketone to 24, followed by base-catalyzed cyclization, afforded the j8-diketone 25. Reaction of 25 with phosphorus oxychloride in dimethylformamide gave the vinylogous acid chloride 26 which afforded the corresponding chloro alcohol on reduction with lithium aluminum tri-f-butoxyhydride. Hydrolysis and concomitant dehydration of this chloro alcohol then gave the desired unsaturated ketone (23). 

During work on the chemistry of penicillin a variety of methods were developed for the synthesis of 5-aminooxazoles. It has been found that cycloisomerization of acylaminocyanoacetic esters (135) by treatment with hydrogen chloride (in alcohol, ether or acetone), phosphorus pent-oxide, or pentachloride leads to 5-aminooxazole-4-carboxylic esters (136),2 61 which have also been obtained by dehydration of acylamino-malonamic esters (137) with phosphorus oxychloride.2... 

A second route to ricinine was suggested by the observation that ethyl 2 4-dihydroxy-6-methyl-nicotinate is obtained from the condensation of ethyl malonate and ethyl /3-aminocrotonate in the presence of sodium ethylate (59). This substituted ethyl nicotinate when converted to the amide by means of alcoholic ammonia and dehydrated with phosphorus oxychloride gives rise to 2 4-dichloro-3-cyano-6-methylpyridine (LXXXYIII). Condensation of LXXXVIII with benzaldehyde followed by oxidation yields the acid (LXXXIX) and this on treatment with sodium methylate... 

The mechanism of dehydration of alcohols by hexamethylphosphortri-amide , phosphorus oxychloride and thionyl chloride in the presence of bases , and sulfur tetrafluoride have been studied. Kirk and Shaw have shown that it is unwise to assume a r/-stereospecificity in dehydration with phosphorus oxychloride or thionyl chloride with basic catalysts. The stereoselectivity is greatly dependent upon the basicity and steric environment of the base. Various steroidal alcohols undergo stereoselective iy -elimination upon treatment with methyl (carboxysulfamoyl) triethylammonium hydroxide inner salt . 

Acetylation of (40) afforded the 3,4-diacetyl derivative, and attempts to further acetylate this product failed to yield a triacetylated product. Passing hydrogen chloride gas through a dry methanolic solution of (40) resulted in the formation of vasicine hydrochloride, indicating dehydration of the tertiary alcohol at C-3 a. Reaction of phosphorus oxychloride with (40) in pyridine yielded chlorodeoxyvasicine. Partial synthesis of (40) was accomplished by heating vasicine and water in a sealed tube at 140—150° for 16 hours. 

Secondary and tertiary alcohols can be dehydrated in dimethyl sulfoxide when heated to 160 -185°C for 14-16 hr to give olefins in yields of 70-85% [6]. The solution is diluted with water, extracted with petroleum ether (30°-60 C), dried, and then distilled. Other acid catalysts that have been reported for dehydration of alcohols are anhydrous or aqueous oxalic [7, 8], or phosphoric acid [9], and potassium acid sulfate [10,11]. In addition, acidic oxides such as phosphorus pentoxide [10-12] and acidic chlorides such as phosphorus oxychloride or thionyl chloride [13] have been reported to be effective as catalysts for the dehydration reaction. 

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