Thionyl chloride dehydration

Know the meaning of dehydration, thionyl chloride, phosphorus trichloride, phosphorus tribromide. 

Nitriles and Isocyanides via Amide Dehydration. Thionyl chloride dehydrates primary amides to form nitriles (eq 8) for example, 2-ethylhexanonitrile is produced in about 90% yield by heating with SOCI2 in benzene. Substituted benzonitriles are readily produced from benzamides. These reactions may also be catalyzed by DMF. A -Alkylformamides may be dehydrated to isocyanides. ... 

In the distilling-flask remains a very small high-boiling fraction of benzoic anhydride (b.p. 366 ), formed by the dehydrating action of the thionyl chloride on the benzoic acid ... 

By the dehydration of primary amides with phosphorus pentoxide or with thionyl chloride, for example ... 

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... 

A simpler nonphosgene process for the manufacture of isocyanates consists of the reaction of amines with carbon dioxide in the presence of an aprotic organic solvent and a nitrogeneous base. The corresponding ammonium carbamate is treated with a dehydrating agent. This concept has been apphed to the synthesis of aromatic and aUphatic isocyanates. The process rehes on the facile formation of amine—carbon dioxide salts using acid haUdes such as phosphoryl chloride [10025-87-3] and thionyl chloride [7719-09-7] (30). 

Monsanto has disclosed the use of carbon dioxide—amine complexes which are dehydrated, at low temperatures, with phosphoryl chloride [10025-87-3] or thionyl chloride [7719-09-7] as a viable route to a variety of aUphatic isocyanates. The process rehes on the facile formation of the intermediate salt (30).REPLACEVariations of this process, in which phosgene is used as a dehydrating agent, have been reported earlier (84). Table 2 Hsts commercially available aUphatic isocyanates. 

Sulfonic acids may be subjected to a variety of transformation conditions, as shown in Figure 2. Sulfonic acids can be used to produce sulfonic anhydrides by treatment with a dehydrating agent, such as thionyl chloride [7719-09-7J. This transformation is also accomphshed using phosphoms pentoxide [1314-56-3J. Sulfonic anhydrides, particulady aromatic sulfonic anhydrides, are often produced in situ during sulfonation with sulfur trioxide. Under dehydrating conditions, sulfonic acids react with substituted aromatic compounds to give sulfone derivatives. 

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. 

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-... 

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 ... 

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). 

The possibility of a cA-elimination has been suggested to explain the course of the thionyl chloride dehydration of the 3a-alcohol (103). 

The reaction of diketosulfides with 1,2-dicarbonyl compounds other than glyoxal is often not efficient for the direct preparation of thiophenes. For example, the reaction of diketothiophene 24 and benzil or biacetyl reportedly gave only glycols as products. The elimination of water from the P-hydroxy ketones was not as efficient as in the case of the glyoxal series. Fortunately, the mixture of diastereomers of compounds 25 and 26 could be converted to their corresponding thiophenes by an additional dehydration step with thionyl chloride and pyridine. 

Reductive amination of dihydropyran (which may be regarded as the dehydration product of the cyclic acetal of 5-hydroxy-pentanal) in the presence of isopropylamine and a trace of acid affords the aminoalcohol, 96. Treatment of this compound with thionyl chloride affords the haloamine, 97. Alkylation of the quinoline, 92, with this halide yields pentaquine (98). ... 

The simplest method of nitrile preparation is the Sj 2 reaction of CN with a primary or secondary alkyl halide, as discussed in Section 20.5. Another method for preparing nitriles is by dehydration of a primary amide, RCONH2. Thionyl chloride is often used for the reaction, although other dehydrating agents such as POCI3 also work. 

Arenediazoisocyanides (Ar —N2NC) were synthesized by Ignasiak et al. (1975) by reaction of arenediazonium ions with formamide and dehydration of the resulting l-aryl-3-formyltriazene with thionyl chloride (Scheme 6-19). These compounds are interesting in the context of the (Z)/( )-isomerism of diazocyanides (see Sec. 6.6). 

It may be pointed out that dehydration of p hydroxy esters with fused potassium hydrogen sulphate, acetic anhydride, phosphoric oxide or with thionyl chloride in benzene solution leads to ap-unsitturated esters containing some Py-unsaturated ester the proportion of the latter depends not only upon the structure of the ester but also upon the dehydrating agent used. I>ehydration occasionally occurs during the reaction itself or upon attempted distillation. 

Thionyl chloride reacts as both a Lewis acid and a Lewis base, and both the S and Se compounds are very reactive toward many other materials. The hydrolysis reactions take place readily, and SOCl2 has such an affinity for water that is used as a dehydrating agent. 

The described procedure is not suitable for all acids. For instance, the acid chloride must not have a boiling point so near that of thionyl chloride that they are inseparable by distillation. Certain high-molecular-weight acids give dehydration products, presumably diketenes e.g., behenic and dihydroxystearic acids. 

Dehydration without rearrangement occurs regioselectively with thionyl chloride in pyridine (Eq. 43). The selenium analogues have shown similar behavior (Eq. 44) 87)... 

Di-2-pyridyl sulphite (343) (from 2-pyridone and thionyl chloride in the presence of triethylamine) transforms primary aliphatic and aromatic amines RNH2 into N-sulphinylamines RN=S=0 and it dehydrates amides ArCONH2 to aryl cyanides, aldehyde oximes RCH=NOH (R = Cxlf 7. 4-MeOCgH4 or PhCH=CH) to the cyanides RCN and A-alkyl- and TV-ary Iformamides RNHCHO to isocyanides RNC. Aliphatic and aromatic... 

This procedure is a modification of preparations of 3-phen)d, sydnone described earlier. The dehydration of N-nitroso-N phenylglycine has also been effected by the use of thionyl chloride and pyridine in dioxane, thionyl chloride in ethertrifluoroacetic anhydride in etherand diisopropylcarbodiimide in water or by reaction of the alkali metal salts of N-nitroso-N-phenylglycine with phosgene or benzenesulfonyl chloride in water or with acetyl chloride in benzene. ... 

Nohira et al. treated N-acylamino acids 195 with thionyl chloride mixed anhydrides 196 were formed below 30°C. The latter compounds gave the first type of hexahydro-2//-3,l-benzoxazin-4-one 197 on triethylamine treatment [77H(7)301]. This reaction was also performed with diexo- and diendo-substituted j8-amino acids 198 yielded the 5,8-methano-2//-3,l-benzoxazin-4-ones 199 via the acyl derivatives 200 (84S345,84T2385). Further homologs were also prepared by the dehydration of N-acylamino acid derivatives (85MI1 88MI3). 

Dehydration of the tertiary alcohol (6.2.5) is accomplished by chlorination of the tertiary alcohol group by thionyl chloride, forming the diene 2-chloro-9-(3-propen-l-iliden)thioxanthene (6.2.6), the addition to which of dimethylamine at high temperature forms the desired chlorprothixene (6.2.7). 

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). 

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