Organic Syntheses Procedure

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Org. Synth. 1998, 75, 184

DOI: 10.15227/orgsyn.075.0184

4-DIMETHYLAMINO-N-TRIPHENYLMETHYLPYRIDINIUM CHLORIDE

[ Pyridinium, 4-(dimethylamino)-1-(triphenylmethyl)-, chloride ]

Submitted by Ashok V. Bhatia¹ , Sunil K. Chaudhary² , and Oscar Hernandez³ .

Checked by Joseph P. Bullock and Louis S. Hegedus.

1. Procedure

A mixture of 30.6 g (0.1 mol) of pure chlorotriphenylmethane (Note 1) and 12.2 g (0.1 mol) of 4-dimethylaminopyridine (Note 2) is placed in a 2-L, three-necked, round-bottomed flask equipped with a dropping funnel and a Y-tube holding a thermometer and a nitrogen (N₂) inlet adapter. To the mixture is added, with continuous stirring, 200 mL of dry dichloromethane (CH₂Cl₂, (Note 3)) through the dropping funnel. After the addition, stirring is continued for an additional 3 hr at 20-25°C under N₂.

To the clear solution is gradually added 1 L of ethyl acetate (Note 4) over 1 hr with continual stirring. The product slowly crystallizes during the addition of ethyl acetate. At the end of the addition, the product slurry is cooled to 5°C by immersing the reaction flask in an ice bath. The product is filtered and washed twice with 100 mL of cold ethyl acetate . Upon drying under vacuum at 50°C for 24 hr, 38.6 g of the product is recovered as a white solid (96% yield, mp 128-131°C) (Note 5).

2. Notes

1. Chlorotriphenylmethane was purchased from Aldrich Chemical Company, Inc. , and crystallized from toluene/petroleum ether.

2. 4-Dimethylaminopyridine was purchased from Aldrich Chemical Company, Inc. , and recrystallized from ethyl acetate/cyclohexane.

3. Dichloromethane was placed over 3 Å molecular sieves for 24 hr prior to use. The checkers used dichloromethane freshly distilled over calcium hydride (CaH₂).

4. HPLC grade ethyl acetate was washed with aqueous 5% sodium carbonate solution, followed by brine. After drying the organic phase over anhydrous potassium carbonate, ethyl acetate was recovered after distillation over CaH₂.

5. Because of the hygroscopic nature of the product, the melting point is somewhat broad and varies with the amount of moisture present in the product. Anal. Calcd for C₂₆H₂₅N₂Cl · 0.9H₂O: C, 74.85; H, 6.48; N, 6.72; Cl, 8.50; O, 3.45. Found: C, 75.16; H, 6.61; N, 6.66; Cl, 8.82; O, 3.64. The sample has the following spectral characteristics: ¹H NMR (300 MHz, CD₂Cl₂) δ: 3.2 (s, 6 H), 6.7 (d, 2 H, J = 7), 7.2-7.3 (m, 15 H), 8.0-8.1 (m, 2 H) ; ¹³C NMR (75 MHz, CD₂Cl₂) δ: 40.3, 106.9, 127.4, 128.0, 128.1, 128.3, 139.1, 147.5 . The checkers dried the product under vacuum at 50°C for 72 hr; shorter drying times resulted in a different, more complex ¹H NMR spectrum. In addition, significant shifts were observed in the ¹³C NMR spectrum depending upon the state of dryness.

Handling and Disposal of Hazardous Chemicals

The procedures in this article are intended for use only by persons with prior training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011 www.nap.edu). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see Chapter 8 of Prudent Practices.

These procedures must be conducted at one's own risk. Organic Syntheses, Inc., its Editors, and its Board of Directors do not warrant or guarantee the safety of individuals using these procedures and hereby disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedures herein.

3. Discussion

Selective protection of a primary alcohol functionality in a molecule has considerable utility in contemporary organic synthesis. Protection of alcohol groups as triphenylmethyl ethers has found applications in the syntheses of a variety of molecules, particularly in the carbohydrate and nucleoside chemistry areas.⁴ ⁵ ⁶ ⁷^,⁸ ⁹ ¹⁰ ¹¹ The authors have shown that tritylation may be accomplished in a facile manner by treating an alcohol with chlorotriphenylmethane and 4-dimethylaminopyridine in a suitable solvent.¹² A postulated intermediate in such a tritylation reaction is 4-dimethylamino-N-triphenylmethylpyridinium chloride.¹³ The proposal was based on our knowledge of the mechanism of the tritylation reaction and on the enhanced nucleophilic properties of 4-dimethylaminopyridine, which would favor formation of a salt such as 1. The use of 1 for tritylation of alcohols and amines offers distinct advantages over traditional tritylation methods using pyridine as solvent. For example, 1 may be used in combination with solvents such as dimethylformamide and dichloromethane to accommodate a variety of starting materials. Moreover, with the use of 1, stoichiometry is better controlled, which in turn enhances selectivity.

A practical, large scale preparation of 1 further enhances the usefulness of the authors tritylation procedure.⁸^,⁹^,¹⁰^,¹¹ The preparation involves N-tritylation of 4-dimethylaminopyridine under mild conditions. Isolation of the product is straightforward and the product may be stored at ambient temperature for extended periods, without degradation.

References and Notes

Chemical Development Department, D-54Z, Abbott Laboratories, North Chicago, IL 60064;
Department of Biology, University of Victoria, Victoria, BC V8W 2Y2, Canada;
U.S. Environmental Protection Agency, Office of Pollution Prevention and Toxics (7402), 401 M Street, S.W., Washington, DC 20460.
Hanessian, S.; Staub, A. P. A. Tetrahedron Lett. 1973, 3555;
Fréchet, J. M. J.; Haque, K. E. Tetrahedron Lett. 1975, 3055;
Reddy, M. P.; Rampal, J. B.; Beaucage, S. L. Tetrahedron Lett. 1987, 28, 23;
Murata, S.; Noyori, R Tetrahedron Lett. 1981, 22, 2107
Leder, I. G. J. Carbohydr. Chem. 1993, 12(1), 95;
Redlich, H.; Lenfers, J. B.; Thormählen, S. Synthesis 1992, 1112;
Morin, C.; Vidal, M. Tetrahedron 1992, 48, 9277;
Shao, X.; Dolder, M.; Tamm, C. Helv. Chim. Acta 1990, 73, 483;
Chaudhary, S. K.; Hernandez, O. Tetrahedron Lett. 1979, 95.
Hernandez, O.; Chaudhary, S. K.; Cox, R. H.; Porter, J. Tetrahedron Lett. 1981, 22, 1491.

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

4-Dimethylamino-N-triphenylmethylpyridinium chloride:
Pyridinium, 4-(dimethylamino)-1-(triphenylmethyl)-, chloride (10); (78646-25-0)

4-Dimethylaminopyridine: HIGHLY TOXIC:
4-Pyridinamine, N,N-dimethyl- (9); (1122-58-3)

Chlorotriphenylmethane:
Methane, chlorotriphenyl- (8);
Benzene, 1,1',1"-(chloromethylidyne)tris- (9); (76-83-5)

Notes

References/EndNotes

Article Compounds

Authors