Dehydration phosphorus oxychloride, pyridine

Dehydration of 17a-hydroxy-20-ketopregnanes can be accomplished by phosphorus oxychloride/pyridine treatment at room temperature for 4 or more days ... 

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)... 

Carbon disulfide has been found to be inert toward attack of HFA even at elevated temperatures (195). Thiocarboxamides react with two molecules of HFA. The intermediates with the likely structure 134 can be dehydrated with phosphorus oxychloride, pyridine (44), or trifluoroacetic acid anhydride (49) to yield A -l,3,5-oxathiazines 135. A retro Diels-Alder reaction takes place with evolution of HFA when 135 is heated to 140°C (44, 45). The heterobutadienes 136 are in equilibrium with the thiazetes 137, which are more stable at ambient temperature (45). 

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-... 

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. 

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

To circumvent the need for strong acid and allow the dehydration of secondary alcohols, reagents have been developed that are effective under mild, basic conditions. One such reagent, phosphorus oxychloride (POCI3) in the basic amine solvent pyridine, is often able to effect the dehydration of secondary and tertiary alcohols at 0 °C. 

Pyridine, as base in dehydration of formamides with phosphorus oxychloride, 41, 13... 

Aromatic isocyanides can also be prepared conveniently by the dehydration of the corresponding formamides by phosphorus oxychloride, but much better results are obtained if the reaction is done in the presence of potassium fer/-butoxide rather than pyridine.6 Neither method of dehydrating formamides has yet been used to prepare methyl or ethyl isocyanide because their low boiling points make them difficult to isolate from the reaction mixture hence, until a suitable dehydration procedure is worked out, they are best made by reaction of the corresponding alkyl iodide with silver cyanide. ... 

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... 

AHC(18)337>. The 3-alkylbenzo[6 ]furans result from cyclodehydration of aryloxyacetones the most common dehydrating agents are sulfuric acid, phosphorus oxychloride and poly-phosphoric acid. The allyl ethers of phenols can be converted to 2-alkyl-2,3-dihydro-benzo[6]furan by heating with polyphosphoric acid, pyridine hydrochloride or magnesium chloride at 180 °C the intermediate o-allylphenol is not isolated. 

Dehydration of hetisine diacetate (126) with phosphorus oxychloride and pyridine followed by basic hydrolysis afforded a mixture of olefins 136 and 137, whose structures were analyzed by H-NMR spectroscopy. These olefins can only be derived from hetisine diacetate if its structure is 126, a fact requiring the structure of hetisinone to be 128. Furthermore, hetisinone is stable to bases, behavior that is consistent with the assigned structure but less likely for either of the alternative /J-ketoalcohols 134 and 135. When hetisinone was heated in D2O-CFI3OD containing sodium deuteroxide, a mixture of deuterated hetisinones was obtained. Mass spectral analysis revealed the presence of 14% d, 53% d2, 24% d3, and 6% dA species. These data further confirmed that hetisinone is correctly represented as 128. 

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,... 

Dehydrations provide the most general approach to 1,4-oxazines , as illustrated by the synthesis of the fully-unsaturated oxazine 457 by dehydration of diketone 456 using phosphorus oxychloride in pyridine (Scheme 212) <1973JOC3433>. 

Mono- or diacyl derivatives that undergo cyclization to benzoxazoles on heating or under the influence of dehydrating agents are formed as intermediates in this reaction [134, 452, 453, 459, 461 173], Phosphorus oxychloride [453, 457], boric anhydride [455, 461, 462], or polyphosphoric acid [134, 471] are used as condensing agents. In particular, 2-hydroxy-5-nitrobenzoxazole, used for the synthesis of antivirus medicines, has been obtained by the reaction of condensation of 4-nitro-2-aminophenol with (NH2)2CO in pyridine [474],... 

In the above study, diols 458 and 459 were separated by preparative high pressure chromatography. A rapid, efficient, and nondestructive separation of dimers in the dl series from those of the meso type which involves no chromatography has also been devised.406 The procedure involves direct dehydration of the 458/459 mixture, preferably with phosphorus oxychloride in pyridine, and treatment of the unpurified hexaenes 464 and 465 with 0.5 molar equivalent of N-methyltriazoline-dione at low temperature. Under such conditions, only the meso isomer enters into Diels-Alder reaction since only the s-cis conformation of its conjugated diene moiety... 

Hemiaminals are available from HFA and amines. A series of similar reactions has been carried out with ammonia (187,189), amines (189), aliphatic, aromatic (258), and fluoroaliphatic acid amides (169). The hemiaminals 95 can be dehydrated with phosphorus oxychloride in pyridine to form 2-hexafluoropropaneimines 96 (187). 

Pictet-Spengler cyclization of L-tryptophan with formaldehyde afforded the monochiral carboxylic acids 20a,b, whereas cyclization with acetaldehyde yielded the diastereomeric carboxylic acids 21a,b (23). Acids 20a,b with a hydrogen at C-1 are enantiomers, but acids 21a,b are diaste-reomers the cis isomer 21a was the major reaction product when the cyclization of L-tryptophan with acetaldehyde was carried out in the presence of sulfuric acid. Direct removal of the carboxy group in these acids is difficult, but it can be accomplished in several steps dehydration of the amides prepared from the acids with phosphorus oxychloride affords nitriles, and the nitrile group can be removed by reduction with sodium borohydride in pyridine-ethanol (31). 

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.

As in the previous example, dehydration in ring C, in this case by means of phosphorus oxychloride in pyridine, gives the A(9)l 1-olefin, 14-1 (Scheme 7.14). Treatment of the resulting intermediate with A-bromoacetamide, or some other source of electrophilic bromide ion, in water (in effect HOBr) leads to the formation of the bromohydrin 14-2. The stereochemistry is dictated by the initial formation of a bridged a-bromonium ion from attack on the more open underside of the molecule. Axial opening by hydroxide then gives the observed bromohydrin (14-2). 

As described previously, thiazolines are versatile intermediates to thiazoles. In addition, thiazoline rings are structural motifs found in numerous natural products. Among a variety of methods for the construction of thiazolines, the cyclodehydration protocol is perhaps most popular. Bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor) is used as the cyclo-dehydrating agent for the conversion of 3-hydroxy thioamide 60 to the bis(thiazoline) 15 <04H(63)773>. A more recent protocol for the cyclodehydration of P-hydroxy thioamides to thiazolines involves pyridine-buffered phosphorus oxychloride as exemplified by the formation of 62 from 61 <04JA12897>. 

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. 

The conversions of lycorine and caranine derivatives to a- and lycoranes take advantage of the stereoselective catalytic reduction of the 3—3a double bond. In these transformations, the configurations of the asymmetric centers at Cub and Cug are the same as in the parent alkaloids. Because of the trans relationship between the Ci-hydroxyl and the Ciiij-hydrogen, dehydration of the alkaloids and their a- and /3-dihydro derivatives occurs readily with phosphorus oxychloride and pyridine to give 1,11b unsaturation. Catalytic reduction of these olefins... 

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