3-Benzyl-5-(2-hydroxyethyl)-4-methyl-1,3-thiazolium Chloride1

[4568-71-2]  · C13H16ClNOS  · 3-Benzyl-5-(2-hydroxyethyl)-4-methyl-1,3-thiazolium Chloride  · (MW 269.79)

(in the presence of bases, catalyst for the preparation of acyloins and benzoins2 from aldehydes, and for addition of aldehydes to electrophilic double bonds3)

Physical Data: mp 141-143 °C.

Solubility: sol H2O, MeOH, EtOH; slightly sol cold MeCN; insol ether, pentane.

Form Supplied in: colorless crystals, widely available.

Analysis of Reagent Purity: 1H NMR; mp.

Preparative Method: Organic Syntheses procedure.2

Handling, Storage, and Precautions: store dry.

Formation of Benzoins and Acyloins from Aldehydes.

Many thiazolium salts catalyze the formation of benzoins from aromatic aldehydes and of acyloins from aliphatic aldehydes in the presence of a base as shown in the preparation of furoin from furan-2-carbaldehyde (eq 1).2

This catalytic reaction has long been known,4 the most prominent salt being thiamine (vitamin B1). Other azolium salts5 and nucleophilic carbenes, or dimers thereof, also catalyze this reaction.6 Chiral thiazolium salts have been used.7 The reaction can be performed as a phase-transfer reaction at preparative scale in water.8 The title reagent (1) has been used in the preparative large-scale formation of acyloins and benzoins in the presence of Triethylamine in ethanol under anhydrous conditions (eq 2).

Simple aliphatic acyloins,9 mixed aliphatic acyloins,10 and acyloins containing other functional groups11 have been prepared.

Formose Reaction.

A very special case of acyloin formation is observed when formaldehyde is used in that the construction of simple sugars occurs. Only some of the numerous possible products are found in the formose mixture.12 A similar result has been reported with ethylbenzothiazolium bromide as catalyst.13

Addition of Aldehydes to Activated Double Bonds.

This reaction has been reviewed.3 (1) in the presence of bases (e.g. Et3N or NaOAc) catalyzes the addition of aliphatic and heterocyclic aldehydes to a,b-unsaturated ketones (to yield g-diketones), esters (to yield g-ketoesters), and nitriles (to yield g-ketonitriles), for example (eq 3).14 This further illustrates the umpolung effect of this reagent on the aldehyde carbonyl reactivity.

This reaction is used in the synthesis of tri- and polyketones,15 cyano ketones,16 1,4-diketones,17 and oxocarboxylic esters.16b,18 Mannich bases (b-dialkylamino ketones) or their quaternary salts can replace the unsaturated ketones.3 a-Keto carboxylic acids can replace the aldehydes, because these readily decarboxylate under the reaction conditions (eq 4).19

Addition of Aldehydes in Presence of Other Reagents.

The presence of Pentacarbonyliron changes the reaction pathway to afford different products (eq 5).

Michael addition of ethyl acrylate to acetoin and transesterification yields the product shown (35%) together with ethyl levulinate (10%).20 For details on additions of aldehydes in presence of oxidants see 3-Benzyl-4-methyl-1,3-thiazolium Chloride.

Related Reagents.

Table 1 shows some widely used 1,3-thiazolium salts analogs of (1) that are especially well suited with aromatic aldehydes for the above benzoin preparations and for aldehyde additions to double bonds.3

Other Reagents.

Sodium Cyanide or Potassium Cyanide are the classical catalysts for benzoin formation from aromatic aldehydes21 and they can also be used for the addition of aromatic aldehydes to activated double-bonds.3 Carboxylic esters and metals such as sodium are used in the classic acyloin condensation22 and its modern variations.23 Numerous other acyl anion equivalents have been described.24

1. (a) Fieser L. F.; Fieser M. FF 1977, 6, 38. FF 1979, 7, 16 FF 1982, 10, 27. (b) Beilstein 1983, 27(III/IV), 1758.
2. Stetter H.; Kuhlmann H. OS 1984, 62, 170.
3. (a) Stetter H.; Kuhlmann H. OR 1991, 40, 407. (b) Stetter H. AG 1976, 88, 695; AG(E) 1976, 15, 639.
4. (a) Breslow R. JACS 1958, 80, 3719. (b) Castells J.; Domingo L.; López-Calahorra F.; Martí J. TL 1993, 34, 517.
5. For example, 1,3,4-thiadiazolium salts: Alemagna A.; Bachetti T. G 1978, 108, 77.
6. (a) Lachmann B.; Steinmaus H.; Wanzlik H.-W. T 1971, 27, 4085. (b) Bis(1,3-dialkylimidazolidin-2-ylidenes): Lappert M. F.; Maskell R. K. CC 1982, 580.
7. (a) Yano Y.; Tamura Y.; Tagaki W. BCJ 1980, 53, 740. (b) Tagaki W.; Tamura Y.; Yano Y. BCJ 1980, 53, 478. (c) Leeper F. J.; Smith D. H. C. CC 1990, 961. (d) Jimenez L.; Diederich TL 1989, 30, 2759.
8. Tagaki W.; Hara H. CC 1973, 891.
9. Stetter H.; Rämsch R. Y.; Kuhlmann, H. S 1976, 733.
10. (a) Stetter H.; Dämbkes G. S 1977, 403. (b) Stetter H.; Dämbkes G. S 1980, 309.
11. Stetter H.; Rämsch R. Y. S 1981, 477.
12. (a) Castells J.; Geijo F.; López-Calahorra F. TL 1980, 21, 4517. (b) Castells J.; López-Calahorra F.; Geijo F. Carbohydr. Res. 1983, 116, 197.
13. Matsumoto T.; Inoue S. CC 1983, 171.
14. Stetter H.; Kuhlmann H.; Haese W. OS 1987, 65, 26.
15. (a) Stetter H.; Basse W.; Kuhlmann H.; Landscheidt A.; Schlenker W. CB 1977, 110, 1007. (b) Stetter H.; Landscheidt A. CB 1979, 112, 1410. (c) Stetter H.; Nienhaus J. CB 1980, 113, 979.
16. (a) Stetter H.; Kuhlmann H. CB 1976, 109, 2890. (b) Stetter H.; Landscheidt A. CB 1979, 112, 2419. (c) Stetter H.; Basse W.; Nienhaus J. CB 1980, 113, 690.
17. (a) Stetter H.; Hilboll G.; Kuhlmann H. CB 1979, 112, 84. (b) Stetter H.; Lappe P. CB 1980, 113, 1890.
18. Stetter H.; Basse W.; Wiemann K. CB 1978, 111, 431.
19. Stetter H.; Lorenz G. CB 1985, 118, 1115.
20. Noels A. F.; Hubert A. J. J. Mol. Catal. 1983, 22, 235.
21. Ide W. S.; Buck J. S. OR 1948, 4, 269.
22. (a) McElvain S. M. OR 1948, 4, 256. (b) Bloomfield J. J.; Owsley D. C.; Nelke J. M. OR 1976, 23, 259. (c) Finley K. T. CRV 1964, 64, 573.
23. Rühlmann K. S 1971, 236.
24. (a) Lever O. W. Jr. T 1976, 32, 1943. (b) Albright J. D. T 1983, 39, 3207.

Heinrich Kuhlmann

RWTH Aachen, Germany

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