Thionyl dehydration with

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... 

Thallium (ITT) fluoride has been prepared by the action of fluorine or bromine trifluoride on thaUium(III) oxide at 300°C. It is stable to ca 500°C but is extremely sensitive to moisture. Thallium (ITT) chloride can be obtained readily as the tetrahydrate [13453-33-3] by passing chlorine through a boiling suspension of HCl in water. It can be dehydrated with thionyl chloride. Thallium (ITT) bromide tetrahydrate [13453-29-7] is prepared similarly, whereas the iodide prepared in this manner is thaUium(I) triiodide [13453-37-7] H" F2-... 

In a similar manner, coccinelline (99) and precoccinelline (100) have been synthesized from 2,6-lutidine (351) (336,450). Thus, treatment of the monolithium derivative (153) of 351 with P-bromopropionaldehyde dimethylacetal gave an acetal, which was converted to the keto acetal (412) by treatment with phenyllithium and acetonitrile. Reaction of 412 with ethylene glycol and p-toluenesulfonic acid followed by reduction with sodium-isoamyl alcohol gave the cw-piperidine (413). Hydrolysis of 413 with 5% HCl gave the tricyclic acetal (414) which was transformed to a separable 1 1 mixture of the ketones (415 and 416) by treatment with pyrrolidine-acetic acid. Reaction of ketone 416 with methyllithium followed by dehydration with thionyl chloride afforded the rather unstable olefin (417) which on catalytic hydrogenation over platinum oxide in methanol gave precoccinelline (100). Oxidation of 100 with m-chloroperbenzoic acid yielded coccinelline (99) (Scheme 52) (336,450). 

Racemic 2-ethylhexanonitrile has been obtained only by the action of phosphorus pentachloride on 2-ethylhexanaldoxime 4 the levorotatory form has been prepared from the active amide by the method described.6 Other amides have been converted to nitriles by dehydration with thionyl chloride.6-6... 

A modified synthesis of vardenafil (2) on a multi-kilogram scale has recently been reported by a group from Bayer (Scheme 4). Benzamidine 12 was prepared in a different manner than described in Scheme 3, because it is difficult to use trimethylaluminium on a large scale. Thus, 2-ethoxybenzamide was dehydrated with thionyl chloride to give 2-ethoxybenzonitrile, which was treated with hydroxyl amine hydrochloride to afford the /V-hydroxybenzamidine 19. Catalytic hydrogenation of 19... 

The 1,3,4-oxadiazole moiety, in analogy to the 1,2,4-oxadiazole discussed in Section 11.2.5.1, has been used extensively as an ester or amide bioisostere, but also has only recently been applied as an amide replacement in actual peptide segments.1104-1071 The synthesis of the peptide surrogate 1,3,4-oxadiazole derivative 60 is shown in Scheme 18.11021 The N-protected amino acid Boc-Ala-OH (56) was coupled with ethanol to form the ester 57 which was subsequently reacted with hydrazine to form the amino acid hydrazide 58.11(1X1 The hydrazide 58 was reacted with ethyl oxalyl chloride at — 30 °C to room temperature to provide the diacylhydrazide 59. This intermediate was subsequently dehydrated with thionyl chloride in refluxing toluene to form the desired 1,3,4-oxadiazole 60 in >95% ee. Although the overall yields are only moderate, the reported enantioselectivities of the final compounds are very good (Table 4).11021... 

Olah et al.466 observed immediate formation of protonated benzenesulfinic acid upon addition of SO2 to benzenium ion formed in H SO3F-Sb I 5-SO2C11 solution at —78°C. Based upon this observation, Laali and Nagvekar467 developed a method for the synthesis of aromatic sulfoxides [Eq. (5.169)]. Product formation was interpreted in terms of dehydration of protonated benzenesulfinic acid followed by nucleophilic attack by the aromatic to the formed arenesulfinyl cation. Mixed sulfoxides (4-fluorophenyl-4-methylphenyl and 4-fluorophenyl-3-trifluoromethyl sulfoxides) were also prepared by sequential addition of the two aromatics. The direct synthesis of symmetric diaryl sulfoxides in high yields (room temperature, 2—48 h, 50-95%) has been reported through the electrophilic activation of thionyl chloride with triflic acid.468... 

A variety of conditions have been employed to convert o-quinone dioximes into benzofurazans, including dehydration with acetic anhydride, thionyl chloride, sulfuric acid, and phenyl isocyanate, and steam distillation in the presence of alkali. Alternatively, cyclization may be achieved by boiling with aqueous alkali or thermolysis of the corresponding dioxime diacetates or dibenzoates. 

Conditions for the ring closure of readily available 3-(2-hydroxy-2-phenylethyl)-2-iminotetrahydro-l,3-thiazole (263) (82S511) to (262), the racemate of the anthelmintic tetramisole, involve (a) dehydration with concentrated sulfuric acid or (b) reaction with thionyl chloride, phosphorus oxychloride or phosphorus pentachloride in the presence of base followed by dehydrochlorination (66JMC545,68JOC1350). 

A few related observations deserve comment. The presence of an ii-keto function completely inhibited solvolysis of the I2j0-sulphonates by its opposed inductive effect, but did not prevent the tosylhydrazone decomposition and rearrangement [1087. This may be a reflection of the exceptionally low activation energy for the decomposition of an aliphatic diazo-nium ion into a carbonium ion and molecular nitrogen (p. 316). Rather surprisingly, the Cps) cyanohydrin (15) undergoes similar rearrangement on dehydration with thionyl chloride/ pyridine [108,11 ]. 

Nitriles may be prepared from amides by dehydration with phosphorus pentoxide, phosphorus oxychloride or thionyl chloride (Scheme 3.87). 

By reaction with phenyl lithium, mesembrine produced phenyl-mesembrinol (XVI) which was dehydrated with thionyl chloride to a mixture of two isomeric phenylmesembrenes (XVII). Methylation and Hofmann degradation of the mixture of methiodides afforded a uniform des-iV-methylphenylmesembrene (XVIII). Methylation of XVIII and Hofmann degradation of the resulting methiodide yielded, besides ethylene and trimethylamine, 3,4-dimethoxy-p-terphenyl (XIX). The isolation of 3,4-dimethoxy-p-terphenyl served to locate the position of the keto group. 

The cosmenes (2,6-dimethyl-l,3,5,7-octatetraenes, 19k, 29B) have been synthesized from the ocimenes (26). Singlet oxygen followed by reduction of the hydroperoxides obtained yielded a mixture of trienols (Scheme 3), from which the naturally occurring ocimenols (30, see below) could be dehydrated with thionyl chloride at 0°. ... 

It was reasonable to assume, from the preceding information, that bikhaconitine probably is represented by structure CCLXVIII, which differs from pseudaconitine only in that the latter has a C-3 hydroxyl. Accordingly, to prove or disprove this hypothesis, pseudaconitine (CCLIII) was dehydrated with thionyl chloride 129) in the same manner... 

Earlier it was indicated (Schemes 5, 7, 10) that the hydroxy acetate (42) was transformed into the drimenol (2) [49], its acetate (12) [42] or a mixture of the drimenol (2) and the albicanol (43) [39]. Authors [55] accomplished the targeted synthesis of the albicanol (43) and its acetate (68) starting with the hydroxy acetate (42) (Scheme 12). The hydroxy acetate (42) was dehydrated with thionyl chloride into the mixture of acetates (12), (67) and (68), which was subjected to oxidation with m-CPBA. On that treatment the acetates (12) and (67) are selectively oxidised, but the acetate (68) remained unreacted. The latter was than isolated by chromatography and saponified into the albicanol (43). The overall yield of the albicanyl acetate (68) and the albicanol (43) was 61% (at the saponification step the yield of (43) was quantitative). Barrero et al. 

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 . 

Although the Hemetsberger reaction is clearly a powerful synthesis of indole-2-carboxylates, some problems are encountered in addition to the occasional mixture of nitrene cyclization products. Indeed, often the aldoliza-tion route to the 2-azidocinnamates proceeds poorly. This can be obviated at lower temperatures (-30 °C) to stop the reaction at the azido alcohol stage. Subsequent dehydration with thionyl chloride in pyridine or triethylamine afforded the 2-azidocinnamates. This two-step process was superior to the conventional one-step aldolization/ dehydration reaction, as found by Murakami and coworkers [67]. Tercel s group also observed that a low temperature (-78 °C) aldol condensation, isolation of the azido... 

Dehydration with thionyl chloride-dimethylformamide Nitriles from carboxylic acid amides... 

A similar procedure as above has been applied to the synthesis of 4-cyano-l-(N,N-diisopropylcarbamoyl)cubane in 95% yield from its amide by dehydration with thionyl chloride [1106]. It was found that treating the amide with thionyl chloride in DMF or under reflux conditions resulted in its decomposition. This could be avoided if TMEDA was added in 4.7-fold molar excess with respect to the amide. TMEDA seems to play a particular role if triethylamine was used instead, substantial decomposition occurred. 

A high-affinity non-steroidal androgen receptor ligand 1470 has been designed, of which a fragment, 2-iodo-4-nitrobenzonitrile, has been synthesized from its carboxamide 1468 by dehydration with thionyl chloride in 80% yield [1116]. 

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