Primary thionyl chloride

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

The carbonyiation of o-diiodobenzene with a primary amine affords the phthalimide 501 [355,356]. Carbonyiation of iodobenzene in the presence of (9-diaminobenzene (502) and DBU or 2,6-lutidine affords 2-phenylbenzimida-zole (503)[357, The carbonyiation of aryl iodides in the presence of pentaflnor-oaniline affords 2-arylbenzoxazoles directly, 2-Arylbenzoxazole is prepared indirectly by the carbonyiation of (9-aminophenol[358j. The optically active aryl or alkenyl oxazolinc 505 is prepared by the carbonyiation of the aryl or enol triflates in the presence of the opticaly active amino alcohol 504, followed by treatment with thionyl chloride[359]. 

Direct halogenation of sucrose has also been achieved using a combination of DMF—methanesulfonyl chloride (88), sulfuryl chloride—pyridine (89), carbon tetrachloride—triphenylphosphine—pyridine (90), and thionyl chloride—pyridine—1,1,2-trichloroethane (91). Treatment of sucrose with carbon tetrachloride—triphenylphosphine—pyridine at 70°C for 2 h gave 6,6 -dichloro-6,6 -dideoxysucrose in 92% yield. The greater reactivity of the 6 and 6 primary hydroxyl groups has been associated with a bulky halogenating complex formed from triphenylphosphine dihaUde ((CgH )2P=CX2) and pyridine (90). 

With phenols, thionyl chloride forms the aryl chlorides only in exceptional cases, eg, with ttinitrophenol (picric acid). The reaction of thionyl chloride with primary amines produces thionylamines. 

Health nd Safety Factors. Thionyl chloride is a reactive acid chloride which can cause severe bums to the skin and eyes and acute respiratory tract injury upon vapor inhalation. The hydrolysis products, ie, hydrogen chloride and sulfur dioxide, are beheved to be the primary irritants. Depending on the extent of inhalation exposure, symptoms can range from coughing to pulmonary edema (182). The LC q (rat, inhalation) is 500 ppm (1 h), the DOT label is Corrosive, Poison, and the OSHA PEL is 1 ppm (183). The safety aspects of lithium batteries (qv) containing thionyl chloride have been reviewed (184,185). 

Because tertiary alcohols are so readily converted to chlorides with hydrogen chloride, thionyl chloride is used mainly to prepare primary and secondary alkyl chlorides. Reactions with thionyl chloride are nonrrally carried out in the presence of potassium carbonate or the weak organic base pyridine. 

Thionyl imide, HNSO, is a thermally unstable gas, which polymerizes readily. It can be prepared by the reaction of thionyl chloride with ammonia in the gas phase. Organic derivatives RNSO have higher thermal stability, especially when R = Ar. The typical synthesis involves the reaction of a primary amine or, preferably, a silylated amine with thionyl chloride. A recent example is the preparation of FcNSO (Fc = ferrocenyl) shown in Eq. 9.8. In common with other thionylimines, FcNSO readily undergoes SO2 elimination in the presence of a base, e.g., KO Bu, to give the corresponding sulfur diimide FcNSNFc. 

Primary and secondary alcohols are best converted into alkyl halides by treatment with either thionyl chloride (SOCl2) or phosphorus tribromicle (PB ). These reactions, which normally take place readily under mild conditions, are less acidic and less likely to cause acid-catalyzed rearrangements than the HX method. 

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. 

When thionyl chloride is used, diaryl sulfoxides are usually the main products. Unsymmetrical diaryl sulfides can be obtained by treatment of an aromatic compound with an aryl sulfenyl chloride (ArSCl) in the presence of a trace amount of iron powder.Aromatic amines and phenols can be alkylthiolated (giving mostly ortho product) by treatment with an alkyl disulfide and a Lewis acid catalyst. With certain substrates (primary amines with a chloro group, or a group not replaceable by chloro, in the para position), treatment with S2CI2 and NaOH gives thiophenolate salts ... 

Alcohols are commonly converted into the corresponding halogen on treatment with agents such as thionyl chloride in order to provide suitable sites for further variation in functionality. For example, treatment of primary alcohol 81 with thionyl chloride leads to chloro derivative 82 (Equation 16) <1997JME2196>. 

The synthesis of 1,3-selenazoles from A -phenylimidoyl isoselenocyanates has been reported. N-phenylimidoyl isoselenocyanates 94 are prepared from N-phenylbenzamides 92. Treatment of 92 with thionyl chloride affords N-phenylbenzimidoyl chlorides 93, which yield imidoyl isoselenocyanates 94 on reaction with potassium isoselenocyanate. The imidoyl isoselenocyanates 94 were transformed into selenoureas 95 with either ammonia or primary or secondary amines. Reaction of 95 with an activated bromomethylene compound such as bromoacetophenone in the prescence of a base gave the 1,3-selenazole 97 via the salt 96 <00HCA1576>. 

In contrast to uridine,389 cytidine does not yield a 5 -chloro-5 -deoxy derivative on reaction with N,N-dimethyl(chlorometh-animinium) chloride instead 2,2 -anhydrocytidine is formed.395 However, thionyl chloride or bromide in hexamethylphosphor-amide at room temperature achieves this selective replacement of the primary hydroxyl group of halogen in cytidine, and also in adenosine, in respective yields of 80 and 75% for the chloro compounds, and 55 and 30% for the bromo analogs.396... 

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... 

Thionyl chloride nitrate can be used for the selective nitration of primary hydroxy groups in the... 

Thionyl chloride (SOCI2) has often been used as a dehydrating agent for primary, secondary, as well as tertiary p-hydroxy amides. With primary hydroxyl amides, the intermediate p-chloro amide can usually be isolated, which will then... 

Wuts and co-workers recently reported that the Vilsmeier reagent is superior to thionyl chloride for the cyclodehydration of primary and secondary p-hydroxy amides to prepare oxazolines, in particular, for oxazoline 18b, which is used in Taxol synthesis (Scheme 8.10). Some other examples are shown in Table 8.5 (Fig. 8.3). As expected, inversion of configuration at the alcohol bearing carbon atom is observed. Of the examples examined, serine afforded low yields due to the formation of dehydroalanine. The reaction is conveniently carried out in pyridine at room temperature. p-Chloro amides are also formed, which can be converted to the oxazoline with DBU, generally using the same mixture without isolation. The... 

The reaction of primary or secondary alcohols with thionyl chloride is a general method far preparing the corresponding chlaro compounds. In the first step a chlorosulfue ROSOG is formed from which S02 is eliminated in a relatively slow step. This decomposition is... 

Inhibitors of the blood clotting factor thrombin would in principle prove useful in preventing inappropriate clot formation that potentially leads to stroke and heart attack. Reaction of the carboxylic acid (56-2) with thionyl chloride leads to the corresponding acid chloride (56-3). Treatment of that intermediate with the substituted pyridyl amine (56-1) leads to the amide (56-4). Catalytic hydrogenation of (56-4) reduces the nitro group to the primary amine (56-5). Condensation of that ortho-diamine with the carboxyhc acid (56-6) in the presence of carbonyl diimidazole... 

Gerrard [11] had shown earlier that the slow addition of 0.5 mole of thionyl chloride to a mixture of pyridine (1.0 mole) and hydroxy compounds (n-butyl, M-amyl, or ethyl lactate—0.1 mole) gives pyridine hydrochloride and good yields of the sulfite (see Eq. 4). Primary and secondary alcohols with an aromatic nucleus in the a-position give chlorides in the absence of catalysts [12], For example, diphenylmethanol gives the chloride even at —78°C. Sulfites derived from tertiary alcohols are not known. The further addition of thionyl chloride converted the sulfite to the chlorosulfinate (see Eq. 5 and Table I). 

Konovalova and Orekhov103 demonstrated that the primary hydroxyl group in platynecine is more reactive to acylation than the secondary. For example, use of more or less drastic conditions yields platynecine di- or mono-benzoate, respectively. Pyrrolizidine alcohols can be esterified with inorganic acids e.g., mild treatment of platynecine with thionyl chloride yields the cyclic sulfite ester hydrochloride79 (see Section III, A). 

Photoilissociution. Few photochemical studies of thionyl chloride have been made. In the near ultraviolet (lash photolysis Donovan et al. (306) have found Cl and SO in absorption. Since the amounts of SO formed tire much less than those of OSCI2 decomposed, they have concluded the primary... 

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