Thionyl amide

H. Schiff1 thought that he had made thionyl amide, S0(NH2)2, bv the action of thionyl chloride on ammonia, but A. Michaelis showed that the yellow product so obtained was only a mixture of nitrogen sulphide, and ammonium tri- and tetra-thionates. A. Mente obtained a similar product by the action of ammonium carbonate on thionyl chloride. 

These speculations have not so far been confirmed. In the reaction between thionyl chloride and ammonia, using liquid ammonia and cooling carefully, a compound with sulfur and nitrogen in the atomic ratio of 1 2 does indeed result (87) but it shows the same absorption spectrum in solution as salts of HOSN, so that its structure is probably not that of an amide of sulfurous acid, but of the isomeric ammonium salt NH4(OSN). This salt goes over very readily to (LII). Meslans experiments could not be confirmed either by Moissan and Lebeau (97, 98, 99) or in later work, although it was thought possible that thionyl amide is formed from OSF2 and NH3 (96). 

It is not surprising that thionyl amide (LV) has hitherto not been obtained. Its analog, sulfurous acid, has also not been made in the pure state and readily decomposes to SOa, so that one can expect OS(NH2)2 to react in an analogous way. 

Amides, anilides and p toluidides. The dry acid is first converted by excess of thionyl chloride into the acid chloride ... 

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

By treatment of this oxime with phosphorus pentachloride or thionyl fhloride in ether solution, smooth conversion into benzanilide, m.p. 163°, results. The change of any oxime into a substituted amide under the conditions mentioned is usually termed the Beckmann rearrangement. The above example may be represented ... 

Amino-pyridazines and -pyridazinones react with monomethyl- or iV,A-dimethyl-formamide and other aliphatic amides in the presence of phosphorus trichloride, thionyl chloride, phosgene or benzenesuUonyl chloride to give mono- or di-alkylaminomethyl-eneamino derivatives. The same compounds can be prepared conveniently with A,iV-dimethylformamide dimethyl acetal in high yield (Scheme 50). 

Properly substituted isoxazolecarboxylic acids can be converted into esters, acid halides, amides and hydrazides, and reduced by lithium aluminum hydride to alcohols. For example, 3-methoxyisoxazole-5-carboxylic acid (212) reacted with thionyl chloride in DMF to give the acid chloride (213) (74ACS(B)636). Ethyl 3-ethyl-5-methylisoxazole-4-carboxylate (214) was reduced with LAH to give 3-ethyl-4-hydroxymethyl-5-methylisoxazole (215) (7308(53)70). 

Benzisothiazoles are best prepared by oxidative cyclization of o-aminothiobenz-amides (see Section 4.17.9.1.1), reaction of o-toluidines with thionyl chloride (see Section 4.17.9.2.1) or by sulfuration of 2,1-benzisoxazoles (see Section 4.17.10.2). 1,2-Benzisothiazoles can also be prepared from o-disubstituted benzene compounds, cyclodehydration of o-mercaptobenzaldoximes or oxidative cyclization of p-mercaptobenzylamines (see Section 4.17.9.1.1) being the most convenient. Both series of benzo compounds are readily substituted at the 5- and 7-positions by electrophilic reagents. 

Altanserin (100) is a representative of the thiaquinazolinones. This serotonin antagonist is said to prevent gastric lesions. One method for preparation of this compound involves first preparation of isothiocyanate derivative 99, by reacting 4-fluorobenzoylpiperidine with 2-bromoethylamine and then converting the intermediate to the isothiocyanate with thionyl chloride and base. Condensation of 99 with methyl anthranilate (98) probably proceeds initially to a thiourea. Cyclization by ester-amide interchange leads to altanserin (100) [28]. 

Diethanol methylamine Sodium amide Sulfuric acid Hydrogen chloride Thionyl chloride Benzyl cyanide Ethanol ... 

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. 

A classical procedure for the synthesis of the A-(1-chloroalkyl)amides1 or carbamates68 involves substitution of the hydroxy group in stable A-( 1-hydroxyalkyl)amides (or carbamates) by a halogen function with reagents such as thionyl chloride, phosphorus pentachloride, phosphorus pentabromide, etc. In certain cases merely heating in concentrated hydrochloric or hydrobromic acid suffices1. 

Many procedures for the formation of carboxylic acid amides are known in the literature. The most widely practiced method employs carboxylic acid chlorides as the electrophiles which react with the amine in the presence of an acid scavenger. Despite its wide scope, this protocol suffers from several drawbacks. Most notable are the limited stability of many acid chlorides and the need for hazardous reagents for their preparation (thionyl chloride, oxalyl chloride, phosgene etc.) which release corrosive and volatile by-products. Moreover, almost any other functional group in either reaction partner needs to be protected to ensure chemoselective amide formation.2 The procedure outlined above presents a convenient and catalytic alternative to this standard protocol. 

The by-products are both gaseous and the excess of thionyl chloride (b.p. 78°) may be readily removed by distillation. Interaction of the acid chloride with ammonia solution, aniline or p-toluidiiie yields the amide, anilide or p-toluidide respectively ... 

The traditional method for transforming carboxylic acids into reactive acylating agents capable of converting alcohols to esters or amines to amides is by formation of the acyl chloride. Molecules devoid of acid-sensitive functional groups can be converted to acyl chlorides with thionyl chloride or phosphorus pentachloride. When milder conditions are necessary, the reaction of the acid or its sodium salt with oxalyl chloride provides the acyl chloride. When a salt is used, the reaction solution remains essentially neutral. 

Amide bond is an effective anchor to connect CNTs to substrate surfaces. Lan et al. [52] covalently assembled shortened multi-walled carbon nanotubes (s-MWNT) on polyelectrolyte films. The shortened MWNT is functionalized with acyl chloride in thionyl chloride (SOCl2) before self-assembling. The FTIR spectrum of self-assem-bled MWNT (SA-MWNT) adsorbed on a CaF2 plate modified with PEI/(PSS/PEI)2 shows two characteristic absorption peaks at 1646cm-1 (amide I bond) and 1524cm-1 (amide II bond) resulting from the amide bond formed between the polyelectrolyte films and s-MWNTs. 

Ester 324 is hydrolyzed to acid 325 by refluxing in 10% NaOH. In a reaction with thionyl chloride, acid 325 is converted to acid chloride 326, which is isolated as a solid in 96% yield and consecutively converted into amide 327 in 85% yield. Treatment of amide 327 with LDA extracts a proton from the methyl group. The generated anion is trapped by added benzonitrile. Subsequent cyclocondensation of the obtained imine anion with the amide group provides derivative 328 in 62% isolated yield (Scheme 50) <2003EJM983>. 

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... 

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