Appel s salt

The reaction between triphenylphosphine and tetrahalomethane (CCI4, CBr4) forms a salt known as Appel s salt. Treatment of alcohols with Appel s salt gives rise to the corresponding halides. 

Example 2, Appel s salt is often used as a dehydrating agent... 

In the post-1980 period more attention has been paid to heteropentalene structures. An abundance of new chemistry has been revealed for 4,5-dichloro-l,2,3-dithiazolium chloride ( Appel s salt ),... 

For conjugated structures thermolytic reactions with loss of sulfur have been studied since 1980 and afford various types of cyclic and acyclic products (Section 4.11.5.1). Nucleophilic attack at ring carbon is very characteristic of 1,2,3-dithiazoles (Section 4.11.5.4). This type of reaction was especially prolific with Appel s salt, studied mostly by Appel, Rees and their co-workers. The preferential site of attack is C(5) but nucleophilic substitution may occur at C(4) when the C(5) site is blocked by poorly leaving substituents, see the first edition of Comprehensive Heterocyclic Chemistry (CHEC-I) for examples of 1,2,3-dithiazoles <84CHEC-I(6)924> and 1,2,3-oxathiazoles <84CHEC-l(6)930>. Nucleophilic attack at ring sulfur in 1,2,3-dithiazoles occurs on S(2) (Section 4.11.5.5), see... 

Appel s salt (54) is exhaustively chlorinated by chlorine with ring opening to sulfenyl chloride (55). In the presence of Ij as catalyst the sulfenyl chloride (56) is produced (Scheme 5) <85CB1632>. The similar iodine catalyzed chlorination of chlorodithiazolinone (57) occurs less readily (Equation (6)) <85CB1632>. Without the iodine catalyst, chlorination proceeds slowly to give a mixture containing chlorodisulfides of the type (55). 

The extensively studied Appel s salt can be produced by prolonged chlorination of acetonitrile with S2CI2 (Scheme 24) <85CB1632>. For preparative purposes chloroacetonitrile gives the best yield (85%). Another simple method for synthesis of Appel s salt may be provided by reaction of S2CI2 with ethylamine (yield and conditions of the process not disclosed) <85PS(23)277>. 

In the condensations of o-aminohenzyl alcohol 376 or anthranilic acid 401 with 4,5-dichloro-l,2,3-dithiazolium chloride (Appel s salt) 402, imino-l,2,3-dithiazoles 403 were formed. Heating of the imino alcohol 403 (X = H2) in THE in the presence of NaH afforded an 11 1 mixture of 3,1-benzoxazine 404 and 3,1-benzothiazine 405 in moderate yield. Thermal cyclization of imino acid 403 (X = 0) resulted nearly quantitatively in formation of 3,1-henzoxazin-4-one 406 (Scheme 76) <1995CC1419, 1995J(P 1)2097, 1997SL704>. 

In the NMR spectrum of Appel s salt 88, two different absorptions for the two carbonyl functions were observed at 166.0 and 166.7ppm <1997BSB729> this is reinforced by two C=0 vibrations also present in the IR spectrum. The authors therefore concluded that the rotation about the exocyclic partial C=C bond is restricted by a strong attractive S- -O interaction. 

While studying the chemistry of 4,5-dichloro-l,2,3-dithiazolium chloride (Appel s salt) and its derivatives, Besson reported the synthesis of various benzothiazoles from N-arylimino-l,2,3-dithiazoles, which could be synthesised from commercially available aromatic amines28. In this work, the authors explored a variety of strategies to construct the benzothiazole ring and demonstrated that in all cases the focused microwave methodologies were more productive and under well-defined conditions provided convenient methods for scale-up (Scheme 3.17)28. Comparisons were also made between reactions performed under solvent-free conditions and in the presence of solvent29. It is noteworthy that there is no general rule and some reactions performed in the presence of solvent may sometimes be more convenient than the same dry media reaction. 

Benzyl cyclohexanecarboxylate was prepared in 46% yield when a solution of benzyl alcohol and cyclohexanecarboxylic acid in dichloromethane was treated with 1.2 equivalents of Appel s salt 687 in the presence of 2 equivalents of 3,4-dihydro-2/7-pyrido[l,2-a]pyrimidin-2-one 675 at -78°C... 

One of the most studied microwave-assisted formations of the benzothiazole ring is initiated by an addition-elimination reaction. Treatment of aniline derivatives with 4,5-dichloro-l,2,3-dithiazolium chloride (commonly called Appel s salt) gave 4-chloro-5]-f-l,2,3-iminodithiazoles (47) which are very versatile intermediates in the synthesis of a variety of heterocycles (Scheme 9.15). Besson and coworkers... 

Kim and co-workers used dithiazoles to prepare 3-substituted 2-cyanoquinazolinones. Treatment of methyl anthranilate with Appel s salt in the presence of two equivalents of pyridine fiimished the corresponding methyl-A -(4-chloro-5//-1,2,3-dithiazol-5-ylidene)anthranilate (not shown). Further reaction of the ylidene with methyl amine provided the desired cyanoquinazoline in 73% yield. This work set the framework for Besson and co-workers synthesis of a tricyclic congener of desoxyvasicinone, a compound with cytotoxicity against a murine leukemia P-388 cell line. 

Condensation of 4,5-dichloro-l, 2,3-dithiazolium chloride 23 (Appel s salt) with various ort/zo-halogenated anilines and aminopyridines 22 gives the... 

A similar strategy has been applied in the synthesis of a polyfunctional-ized thiazolo [5,4-fc] pyridine 28 (14T5541).Treatment of the Boc-protected aminodicarbamate 26 with the Appel s salt 23 gives a mixture of mono-Boc and bis-Boc aryliminodithiazoles, which is completely deprotected to afford aryliminodithiazole 27. This dithiazole undergoes copper(I)-mediated cyclization to generate 2-cyanothiazolo [5,4-f)]pyridine 28 in 63% yield from 26 (3 steps) (14T5541). 

The striking improvement in the Niementowski quinazoline synthesis [156, 157] has been fulfilled using microwave irradiation by Besson et al. [158,159] (Scheme 7). Using microwave irradiation and/or Appel s salt, new efficient routes to various substituted and fused quinazolines have been developed by Besson et al. [158,159] and also by others [ 160,161]. 

Besson T, Alexandre F-R, Bereeibar A (2005) mierowave irradiation and/or Appel s salt, new efficient routes to various substituted and fused quinazolines. Tetrahedron 59 141... 

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