Trichloroisocyanuric acid is useful too

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Rhodium
(Chief Bee)
11-26-02 02:48
No 383431

Trichloroisocyanuric acid is useful too
(Rated as: excellent)

Trichloroisocyanuric Acid: A Safe and Efficient Oxidant
Ulf Tilstam and Hilmar Weinmann
Organic Process Research & Development 6, 384-393 (2002) (https://www.rhodium.ws/pdf/trichloroisocyanuric.pdf)

Abstract
The literature on trichloroisocyanuric acid (TCCA) has been reviewed. TCCA is a safe and efficient reagent, useful for chlorination and oxidation even on large scale.

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Aurelius
(Hive Bee)
11-26-02 11:36
No 38356

examples

take look at schemes 12, 16 and 26 (especially part b- hello GBL), 14,19, 27 (part b for benzaldehyde from benzyl alcohol), all of 31, 38 (part c,formation of acid chlorides, part d, formation of cyanides from amides- dehydration reactions)

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Rhodium
(Chief Bee)
11-26-02 12:36
No 383590
Scheme 16 - THF to GBL
(Rated as: good read)

Reaction of 1,3,5-Trichloro-2,4,6-trioxohexahydro-s-triazine with THF in the Presence of Water
J. Org. Chem. 31, 3836 (1966)

In order to moderate the reaction, the reaction flask was placed in an ice bath. To 60 ml (53.28 g, 0.74 mole) of tetrahydrofuran, containing 6 ml of water, was added 23.24 g (0.10 mole) of trichloroisocyanuric acid a t such a rate as to maintain a gentle reflux. Upon addition of the first amount of trichloroisocyanuric acid, a yellow color appeared and quickly faded. A white precipitate formed immediately. After all of the trichloroisocyanuric acid was added, the reaction mixture was allowed to stir overnight. Cyanuric acid precipitated almost quantitatively and was removed by filtration. A small sample of the reaction mixture at this point when subjected to gas chromatography showed a peak at the characteristic retention time for gamma-butyrolactone. The filtrate was combined with 60 ml of ether and extracted three times with 20-ml portions of 5% aqueous sodium bicarbonate. The ether layer was distilled, and found to contain only tetrahydrofuran. The water layer was acidified with aqueous hydrochloric acid, and the water and hydrochloric acid were removed by azeotropic distillation with benzene. The benzene was removed by distillation, leaving 2.55 g (19%) of gamma-butyrolactone, bp 88-89?C/10mmHg, nd 1.4332. The infrared and nmr spectra were identical with those of an authentic sample of gamma-butyrolactone.

The reference for 1,4-Butanediol to GBL is Synth. Commun. 25, 719 (1995)

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Captain_Mission
(Stranger / Eraser)
11-27-02 16:48
No 384010

Ahem...

Post 340852 (Captain_Mission: "GBL from THF using trichloroisocyanuric acid", Novel Discourse)

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Lego
(Hive Bee)
07-30-03 08:17
No 450704

Alcohols to chlorides with cyanuric chloride
(Rated as: excellent)

Cyanuric chloride can also bee used to convert alkyl alcohols to alkyl chlorides.

These two methods has not been posted yet (according to TFSE) and are not on Rhodium's page.

The first method is for lower alcohols (like MeOH or isopropylalcohol):
J. Org. Chem., 1970, 35(11), 3967-3968 (http://www.geocities.com/legochemistry/28.pdf)

Experimental section
A typical preparation involves heating the alcohol (2-20 mol) to 10-20? below its boiling point and then slowly adding powdered cyanuric chloride (1 mol). A Dry Ice trap should be connected via a rubber tube to the top of the reflux condenser in order to trap the low boiling chlorides. After the addition (ca. 1-1.5 hr), the reaction mixture is cooled, filtered, and distilled. If complete conversion to the chloride is desired, excess cyanuric chloride should be added.

The second is for higher alcohols (like benzyl alcohol):
Org. Lett., 2002, 4(4), 553-555 (http://www.geocities.com/legochemistry/27.pdf)
DOI:10.1021/ol017168p

Representative Procedure
Chlorination of (S)-(1-Hydroxymethyl-3-methylbutyl)-carbamic Acid Benzyl Ester
2,4,6-Trichloro-[1,3,5]triazine (1.83 g, 10.0 mmol) was added to DMF (2 mL), maintained at 25 ?C. After the formation of a white solid, the reaction was monitored (TLC) until complete disappearance of TCT, and CH2Cl2 (25 mL) was added, followed by the alcohol (2.39 g, 9.5 mmol). After the addition, the mixture was stirred at room temperature and monitored (TLC) until completion (4 h). Water (20 mL) was added, and then the organic phase was washed with 15 mL of a saturated solution of Na2CO3, followed by 1 N HCl and brine. The organic layers were dried (Na2SO4), and the solvent evaporated to yield (S)-(1-chloromethyl-3-methylbutyl)-carbamic acid benzyl ester, which was isolated without other purifications (2.28 g, 89%).

The candle that burns twice as bright burns half as long

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Aurelius
(Active Asperger Archivist)
07-30-03 19:01
No 450765

R-Cl from R-OH Org. Lett. (2002)4,4, 553-555
(Rated as: excellent)

An Efficient Route to Alkyl Chlorides from Alcohols Using the Complex TCT/DMF

Lidia De Luca, Giampaolo Giacomelli,* and Andrea Porcheddu

Org. Lett., Vol. 4, No. 4, 553-555, (2002)

Abstract:

Efficient conversion of alcohols and beta-aminoalcohols to the corresponding chlorides (and bromides) can be carried out at RT in DCM, using 2,4,6-trichloro-[1,3,5]-triazine and N,N-DMF. This procedure can also be applied to optically active carbinols.

The transformation of alcohols into the corresponding alkyl halides is one of the most studied reactions in organic synthesis, and many reagents can be usually used. Often the conversion requires elaborate reagents and quite drastic reaction conditions. Most of the methods employed utilize reagents such as thionyl chloride,1 phosphorus halides,2 phenylmethyleniminium,3 benzoxazolium,4 Vilsmeyer-Haack,5 and Viehe salts.6 In this context, the development of efficient reagents to use in mild conditions has interested organic chemists. The procedure based on the use of triphenylphosphine-carbon tetrahalides seems to meet these requirements but suffers the inconvenience of generating stoichiometric quantities of triphenylphosphine oxide as byproduct. To resolve these drawbacks, (chloro-phenylthiomethylene)dimethylammonium chloride was reported as a mild reagent for selective chlorination and bromination of primary alcohols.7 However, the reagent has to be prepared through a two-step procedure, that requires flash-chromatography workup. Other solutions may be the use of polymer-supported triphenyl phosphine or a filterable phosphine source such as 1,2-bis-(diphenylphosphino)ethane.8 More recently, a mild conversion of alcohols to alkyl halides using halide-based ionic liquids was reported.9

A search of the literature revealed that the treatment of cyanuric chloride, a very cheap reagent, with alcohols furnished the corresponding chlorides.10 The reported procedure implied heating of the mixture to 10-20*C below the boiling point of the alcohol and the use of excess cyanuric chloride for the complete conversion. Indeed, this method did not seem suitable for obtaining complex organic chlorides, such as those derived from amino alcohols. An accurate examination of the former report[sup11[/sup] showed that the treatment of the adduct formed by cyanuric chloride and dimethyl formamide with ethanol resulted in the quantitative formation of HCl and ethyl chloride.

On this basis and following our recent interest in the use of [1,3,5]-triazine derivatives in organic synthesis,12 we report a very mild, efficient, and chemoselective procedure for the quantitative conversion of alcohols into the corresponding alkyl chlorides (Scheme 1).

Scheme 1:

R-OH + TCT/DMF in DCM @ RT to give R-Cl

The procedure is based on the reaction of 2,4,6-trichloro-[1,3,5]-triazine (TCT) with DMG, followed by the addition of a DCM solution of 1mol. eq. of the alcohol. At 25*C, this system effects rapidly the quantitative conversion of the alcohols to the corresponding chlorides (Table 1), which can be recovered chemically pure after a simple aqueous workup that removes the triazine byproducts. The reaction is generally fast, requiring from 10-15 minutes to 4 hours for completion in most of the cases. Reduced rates were observed with sterically constrained alcohols, such as borneol and neopentyl alcohol. As in other cases, 2-phenylsulfanyl-1-ethanol reacts very slowly (ca. 72hours). Reaction of diols gave monochlorination using 1 mol. eq. of the diol, and the conversion to dichloride is complete only using 0.5mol. equivalent. At least with the optically active alcohols we have tested, the data collected show that the reaction occurs with inversion of configuration at the chiral center.13,14

Alkyl bromides can obtained by addition of sodium bromide and the alcohol to the TCT/DMF mixture in DCM. However, in this case, a noticeable amount of the alkyl chloride may be recovered as byproduct.15 Use of sodium iodide did not lead to the formation of alkyl iodides.16

Most interestingly, the reaction is applicable for the synthesis of N-protected beta-amino chlorides. Under the usual conditions, N-protected beta-amino alcohols are in fact converted to the corresponding chlorides, with slightly reduced rates. (Table 2); however, the reaction is complete within 4 hours. Moreover, the method is compatible with the common N-protecting groups, and no deprotection was noted even with N-Boc-protected amino acids, if working in the presence of NaHCO3.

The stereochemical results indicate the occurrence of a Sn2 reaction that may be consistent with the mechanism depicted in Scheme 2. The Vilsmeyer-Haack-type complex should add the hydroxyl group of the alcohol to form the cationic species 3; subsequent nucleophilic attack of halide ion should produce the corresponding halide.17

In conclusion, the procedure reported here is operationally simple and allows a rapid and high-yielding conversion of alcohols to the corresponding chlorides and bromides under very mild conditions. The method seems to be more convenient with respect to other reports and can be used as a valid alternative to other methods, so avoiding tedious purifications or the use of more toxic reagents.

Acknowledgements This work was financially supported by the University of Sassari (Fondi ex-60%).

Note Added after ASAP:

There was a nitrogen omitted from the second reagent above the arrow in the abstract in the version posted ASAP on 1/17/02. The print and final Web version was posted (1/23/02).

Supporting Information Available:

Physical and spectroscopic data for all unknown compounds and experimental procedures. This material is available free of charge via the Internet at http://pubs.acs.org.

References:

(1)For a review, see: Larock, R.C. Comprehensive Organic Transformations, 2nd ed.: John Wiley & Sons: (1999), 689.
(2)Weiss, R.G.; Snyder, E.I. J. Chem. Soc. Chem. Commun., (1968), 1358; JOC, (1972), 36, 403.
(3)Fujisawa, T. Iida, S; Sato, T. Chem. Lett., (1977), 1173.
(4)Mukaiyama, T; Shoda, S. I.; Watanabe, Y. Chem. Lett., (1977), 383.
(5)Benazza, T; Uzan, R.; Beaupere, D; Demailly, G. Tetrahedron Lett., (1992), 33, 4901.
(6) Benazza, T; Uzan, R.; Beaupere, D; Demailly, G. Tetrahedron Lett., (1992), 33, 3129.
(7)Gomez, L; Gellibert, F; Wagner, A; Mioskowski, C. Tetrahedron Lett., (2000), 41, 6049.
(8)Pollastri, M; Sagal, J.F.; Chang, G. Tetrahedron Lett., (2001), 42, 2459.
(9)Ren, R.X.; Xin, Wu; J. Org. Lett., (2001), 3, 3027.
(10)Sandler, S.R.; JOC, (1970), 35, 3967.
(11)Gold, H. Agnew. Chem., (1960), 72, 956.
(12)(a) Falorni, M; Porcheddu, A; Taddei, M. Tetrahedron Lett., (1999), 40, 4395.
(b)Falorni, M. Giacomelli, G.; Porcheddu, A.; Taddei, M. JOC, (1999), 64, 8962.
(c)Falchi, A; Giacomelli, G; Porcheddu, A; Taddei, M. Synlett, (2000), 275.
(d)De Luca, L; Giacomelli, G.; Porcheddu, A; Taddei, M. JOC, (2001), 66, 2534.
(e)De Luca, L; Giacomelli, G.; Porcheddu, A; Org. Lett., (2001), 3, 1519.
(f)De Luca, L; Giacomelli, G.; Porcheddu, A;Org. Lett., (2001), 3, 3041.
(g)De Luca, L; Giacomelli, G.; Porcheddu, A; JOC, (2001), 66, 7907.
(13)Giacomelli, G.; Lardicci, L. JOC, (1981), 46, 3116.
(14)Kwart, H.; Givens, E.N.; Collins, C.J. JACS, (1969), 91, 5532.
(15)The bromide can be recovered by accurate distillation or flash chromatography.
(16)No result was obtained even with the addition of tetrabutylammonium iodide. The presence of tetrabutylammonium bromide causes the formation of the alkyl bromide in low yields.
(17)Representative Procedure: Chlorination of (S)-(1-hydroxymethyl-3-methylbutyl)-carbamic Acid Benzyl Ester.

2,4,6-trichloro-[1,3,5]-triazine (1.83g, 10mmol) was added to DMF (2ml), maintained at 25*C. After the formation of a white solid, the reaction was monitored (TLC) until complete disappearance of TCT, and DCM (25ml) was added, followed by the alcohol (2.39g, 9.5mmol). After the addition, the completion (4hours). Water (20ml) was added, and then the organic phase was washed with 15ml of a saturated solution of sodium carbonate, followed by 1N HCl and brine. The organic layers were dried with sodium sulfate, and the solvent evaporated to yield (S)-(1-chloromethyl-3-methylbutyl)-carbamic acid benzyl ester, which was isolated without purifications. (2.28g, 89%)

Typical yields for R-Cl is 95%+, and for R-Br, yields are 70%+ Many examples are found in the tables. (not shown in this post)

Act quickly or not at all.

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Rhodium
(Chief Bee)
11-20-03 16:24
No 472073

TCICA related articles by G.A. Hiegel
(Rated as: good read)

G.A. Hiegel and M. Nalbandy, "The Oxidation of Alcohols to Ketones Using Trichloroisocyanuric Acid", Synth. Commun., 22, 1589-1595 (1992).

G.A. Hiegel, "Trichloroisocyanuric Acid", in Encyclopedia of Reagents for Organic Synthesis, L. A. Paquette, Ed., John Wiley & Sons, Ltd., Chichester, West Sussex, England, Vol. 7, p. 5072-5073 (1995).

G.A. Hiegel, Christopher D. Bayne, Yariv Donde, Gerald S. Tamashiro, and Lisa A. Hilberath, "The Oxidation of Aldehydes to Methyl Esters Using Trichloroisocyanuric Acid", Synth. Commun., 26 (14) 2633-2639 (1996).

G.A. Hiegel and Afshin K. Chaharmohal, "The TCICA Test for Distinguishing Primary and Secondary Alcohols", J. Chem. Ed., 74 (4), 423 (1997).

G.A. Hiegel, Jenny Ramirez, and Robert K. Barr, "Chlorine Substitution Reactions Using Trichloroisocyanuric Acid with Triphenylphosphine", Synth. Commun., 29 (Cool, 1415-14-19 (1999).

G.A. Hiegel, Christine Juska, and Michelle Kim, "The TCICA Test for Distinguishing Aldehydes and Ketones", J. Chem. Ed., 78 (Cool, 1105-1106 (2001).

G.A. Hiegel and Mark Rubino, "Conversion of Alcohols into Alkyl Halides Using Trichloroisocyanuric Acid with Triphenylphosphine", Synth. Commun., 32 (17), 2691 (2002).