(1; R = Me)

[43180-39-8]  · C9H13NS  · Dimethyl(phenylthiomethyl)amine  · (MW 167.30) (2; R = Et)

[13865-52-6]  · C11H17NS  · Diethyl(phenylthiomethyl)amine  · (MW 195.36)

(sources of the R2NCH2+ synthon for reactions with many organometallics;6 phenylthiomethylation reagents for enamines;12 a modified Sommelet-Hauser rearrangement route15 from benzyl bromides to o-tolualdehydes)

Physical Data: (1) bp 112-116 °C/9-11 mmHg. (2) bp 110-112 °C/5-6 mmHg; d 0.9878 g cm-3; n25D 1.5500.

Preparative Methods: PhSH + R2NH + CH2O (71%);1 PhSH + CH2=+NMe2 I- (80%).2

Dialkylaminomethylation of Nucleophiles.

The dialkyl(phenylthiomethyl)amines are good sources of the R2NCH2+ synthon for reactions with alkyl,3 allyl (eq 1),4 and aryl5 Grignards, and alkenyl6 copper reagents (eq 2); these C-C couplings give alkyl,3 homoallylic,4 benzylic,5 and allylic6 tertiary amines, respectively. Silyl-7 and germyllithiums8 give the corresponding dialkylaminomethylsilanes and -germanes. An alternative route to Me2NCH2-R (or -Ar) type tertiary amines from Grignards and other organometallics involves the use of methylene immonium salts9 (Eschenmoser salt, CH2=+NMe2 Cl-, is a commercial reagent; see Dimethyl(methylene)ammonium Iodide), and benzotriazole-derived aminals10 or amine N-oxides11 can be used as sources of the R2NCH2+ synthon in general. The above procedures are particularly valuable for the synthesis of tertiary benzylic amines where the usual Mannich conditions do not work owing to insufficient nucleophilicity of the starting aromatic reactant.

Phenylthiomethylation of Nucleophiles.

Under acidic conditions, the dialkylamino moiety becomes the leaving group and PhSCH2+ is thus delivered to a nucleophile. b-Phenylthio ketones are obtained from enamines (eq 3)12 in a procedure that avoids the use of the obnoxious alternative Chloromethyl Phenyl Sulfide.13 However, good yields are only reported with enamines derived from MeCOR (or MeCOAr), and those derived from a-branched carbonyl compounds do not react at all (the chloromethyl sulfide alternative12 is more versatile). Highly reactive aromatics14 (indole, 2-naphthol; eq 4) are phenylthiomethylated in good yield, in contrast to simple phenols and aryl amines, halides, and ethers.

Modified Sommelet-Hauser Rearrangement.

The quaternary ammonium salts from dimethyl(phenylthiomethyl)amine and benzyl bromides give o-tolualdehydes in good yield.15 This reaction was used in two different syntheses,16,17 of juncusol (eq 5; R = H, 87%; R = CO2Me, 54%).16 The product from benzyl bromide and pyrrolidinoacetonitrile18 undergoes an analogous reaction to give o-tolualdehyde in 85% yield. The classical alternatives, such as a reduction of the bromide or its precursor aldehyde to methyl, followed by formylation, cannot compete with these highly expedient synthetic routes.

1. Grillot, G. F.; Thompson, H. G. JOC 1957, 22, 706.
2. Bryson, T. A.; Bonitz, G. H.; Reichel, C. J.; Dardis, R. E. JOC 1980, 45, 524.
3. Sato, Y.; Ban, Y.; Shirai, H. JOM 1976, 113, 115.
4. Miginiac, L.; Mauzé, B. BSF(2) 1968, 2544 (CA 1968, 69, 105 792n).
5. Sato, Y.; Yagi, Y.; Koto, M. JOC 1980, 45, 613.
6. Normant, J. F.; Quirion, J. C.; Masuda, Y.; Alexakis, A. TL 1990, 31, 2879 and earlier work.
7. Sato, Y.; Toyo'oka, T.; Aoyama, T.; Shirai, H. JOC 1976, 41, 3559.
8. Inoue, S.; Urayama, S.; Sugiura, H.; Sato, Y. JOM 1989, 363, 25.
9. (a) Cooper, M. S.; Heaney, H. TL 1986, 27, 5011. (b) Holy, N. L. SC 1976, 6, 539. (c) Volz, H.; Kiltz, H.-H. LA 1971, 752, 86 (CA 1972, 76, 13 941b).
10. Review: Katritzky, A. R.; Rachwal, S.; Hitchings, G. J. T 1991, 47, 2683.
11. Tokitoh, N.; Okazaki, R. BCJ 1988, 61, 735.
12. Suzuki, K.; Sekiya, M. S 1981, 297.
13. Paterson, I.; Fleming, I. TL 1979, 995.
14. Suzuki, K.; Sekiya, M. CL 1979, 1241.
15. Michelot, D.; Lorne, R.; Huynh, C.; Julia, S. BSF(2) 1976, 1482 (CA 1977, 86, 120 129w).
16. Kende, A. S.; Curran, D. P. JACS 1979, 101, 1857.
17. Boger, D. L.; Mullican, M. D. JOC 1984, 49, 4045.
18. Mander, L. N.; Turner, J. V. JOC 1973, 38, 2915.

Tapio A. Hase & Kristiina Wähälä

University of Helsinki, Finland

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