Sciencemadness Discussion Board

Straight chain PTSA esters

Panache - 30-3-2008 at 13:28

Could someone with experience making straight chain esters from PTSA (para toluene sulphonic acid) please post typical reaction conditions. Ideally i believe a primary straight chain alcohol can be used but if other reactants are more favourable that is fine. If possible workup conditions would also be appreciated.
Cheers!!!

Klute - 31-3-2008 at 06:38

I beleive you need the corresponding sulfonyl chloride for that... the acid alone doesn't react well, or not at all. You can't use a dean stark with, say methanol, so from the acid the only practical way i see is reaction alkyl halides with the potasium/sodium salt, if you can't acces orthoformate esters.

On the other hand, if a alkylating agent is seeked, you can make aliphtic sulfonyl chlorides pretty easily! These react with aliphatic alcohols in presence of a base (triethylamine) to form the corresponding sulfonates:

alkylisothioureas, alklylthiocyantes, alkylthiosulfates and sulfides form the corresponding sulfonyl chlorides easily when aqueous solutions are chlorinated in the cold. The sulfonyl chlorides seperate out as solids, and can easily be isolated, then reacted with alcohols.
Alkylisothioureas are easily obtained from the corresponding alcohol or alkylhalides and thiourea, see US2146744, which deals with their preparation and chlorination. Mesylchloride and others avaible easily and cheaply!
Unfortunaly, aromatic sulfonyl chlorides can't be obtained through phenols. You will have to react an aryl iodide with one of the mentionned sulfur compouds and chlorinate that. Brominating toluene and subsequent sulfuration/chlorination could give PTSulfonic chloride along with ring-chlorinated by-products, but I think mesylates are at least as effective as alkylating agents and leaving groups, so why bother.

This scheme opens alot of doors, sulfonates are excellent leaving groups, so you can "reverse" the reagents and effect SN on alcohols etc. Reduction (Zn, H2/cat, etc) of sulfonyl chloride leads to thiols. Other sulfonyl halides (even fluorides) can be obtained with the corresponding halides, not sure of iodine though.

Also chlorination of thiocynates also produce CNCl, which can come out handy (bromination gives CNBr)

I've requested a few papers on the subject in the ref forum if interested.

US h000890 give examples of synthesis of sulfonyl chloride through chlorination of isothioureas and thiosulfates.
Johnson and Sprague have published a few articles on isothioureas chlorination in JACS, i don't have the refs at hand now but can get them.

EDIT: Ah, i forgot, 5% CoCl2 catalyses direct tosylation of alcohols with TsOH in refluxing dichloroethane. DCM, MeCN and toluene can also be used with lower yields:

Cobalt(II) catalyzed tosylation of alcohols with p-toluenesulfonic acid
Subbarayan Velusamy, J. S. Kiran Kumar and T. Punniyamurthy

Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, India Received 23 July 2003; revised 7 October 2003; accepted 17 October 2003

Tetrahedron Letters 45 (2004) 203–205
DOI:10.1016/j.tetlet.2003.10.106

Abstract

—Cobalt(II) chloride hexahydrate (CoCl2.6H2O) has been found to catalyze the tosylation of both aliphatic and aromatic alcohols with p-toluenesulfonic acid (p-TsOH) in high yields in 1,2-dichloroethane under reux (ca. 80 °C). In the case of aliphatic alcohols, secondary alcohols undergo tosylation chemoselectively in the presence of primary hydroxy groups.

Keywords: tosylation; alcohol; p-toluenesulfonic acid; catalyst; cobalt(II) chloride hexahydrate.



[Edited on 31-3-2008 by Klute]

Nicodem - 31-3-2008 at 07:19

Quote:
Originally posted by Panache
Could someone with experience making straight chain esters from PTSA (para toluene sulphonic acid) please post typical reaction conditions. Ideally i believe a primary straight chain alcohol can be used but if other reactants are more favourable that is fine. If possible workup conditions would also be appreciated.
Cheers!!!


Aha, feeling very lazy today? Fear not for there is always someone bored enough to search instead of you. Today such a fool is me:

n-DODECYL (LAURYL) p-TOLUENESULFONATE

And many other examples:

Tosylation of an alcohol; toluene-4-sulphonic acid esters

Protection of an alcohol as a p-toluenesulfonate

SYNTHESIS OF N-(tert-BUTOXYCARBONYL)-β-IODOALANINE METHYL ESTER

6A-O-p-TOLUENESULFONYL-β-CYCLODEXTRIN

CYCLOBUTENE

And all this from only two homepages! Not to mention a couple of thousand examples in chemical journals that you somehow managed not to find. The mere thought of typing "alcohol tosylation" into google just scares me. :P

Panache - 31-3-2008 at 16:33

oooooohhhhhhh
i do appear lazy
must be this hazy
swirl of smoke around my
head
floating just above my
bed
should have checked with Mr.Google
instead
of slapping up this lame-ass
thread

there i wrote a poem to make up for my ultra-super-exothermed laziness
btw thank-you dr Klute and dr nicodem for your reply notwithstandingaforementioned laziness.

Klute - 1-4-2008 at 09:28

If you try out one of these procedures, please let us know. In the futur, i will make a few tosylates myself, having some TsCl and Et3N one hand. I have MeI and most prefered Trimethylphosphate, aswell as EtBr, so i will be aiming for C3 and + esters, so we could see how good the yield are.
My tosyl chloride will need some recrystallization though, at it's caked up and surely degraded in part to TsOH and HCl. There's a neat procedure for purifying it in Purification of Lab. Chem. Uses DCM and pet ether IIRC.

Ah, i also forgot to mention that tosyl chloride can be made from TsOH with polyphosphoric acid or it's esters and a chloride source.

Attachment: Reduction of Organic Sulfonic Acids, Sodium Sulfonates, and Sulfonic Esters to the Corresponding Disulfides with Polypho (727kB)
This file has been downloaded 3648 times

Nicodem - 1-4-2008 at 12:37

In regard to direct O-tosylation of alcohols with TsOH there are also published these two methods (from one Indian group) besides the Co(II) catalysed one mentioned by Klute:

ZrCl4 as an efficient catalyst for selective tosylation of alcohols with p-toluenesulfonic acid.
Das, Biswanath; Reddy, Vtukuri Saidi.
Chemistry Letters, 33 (2004) 1428–1429.
DOI:10.1246/cl.2004.1428

Abstract: Tosylation of alcs. has directly been carried out with p-toluenesulfonic acid in methylene chloride under reflux using ZrCl4 as a catalyst. Primary alcs. were found to be tosylated chemoselectively over secondary alcs.


An efficient and selective tosylation of alcohols with p-toluenesulfonic acid.
Das, Biswanath; Reddy, V. Saidi; Reddy, M. Ravinder.
Tetrahedron Letters, 45 (2004) 6717-6719.
DOI:10.1016/j.tetlet.2004.07.076
(full paper in the attachment)

Abstract: Silica chloride has been found to be an efficient catalyst for facile tosylation of alcs. directly with p-toluenesulfonic acid in methylene chloride under reflux. The process is assocd. with selective tosylation of secondary alcs. over primary alcs.


Just in case you can get ZrCl4 or SiCl4. Otherwise it is also possible to use silver tosylate in substitutions of alkyl bromides yielding the corresponding alkyl tosylates. In the attachment there is a paper that is probably more of interest to Klute than you (in regard to one of his threads) and contains one such example of R-Br + TsOAg => R-OTs + AgBr:

Curcumin and Dehydrozingerone Derivatives: Synthesis, Radiolabeling, and Evaluation for a-Amyloid Plaque Imaging
Eun Kyoung Ryu, Yearn Seong Choe, Kyung-Han Lee, Yong Choi, and Byung-Tae Kim
J. Med. Chem., 49 (2006) 6111-6119.
(full paper in the attachment)


Also, not only the orthoesters give alkyl tosylates in their reaction with TsOH. A similar reaction occurs with phosphite and phosphate esters:

Reaction of phosphorus oxyacid esters with p-toluenesulfonic acid.
Nitta, Yoshihiro; Arakawa, Yasushi; Ueyama, Naoto. Sch
Chemical & Pharmaceutical Bulletin, 34 (1986) 2710-2718.

Abstract: 4-MeC6H4SO3R (I; R = primary alkyl) were prepd. by reaction of I(R = H) with PO(OR)3, P(OR)3, or PhPO(OR)2 in refluxing solvent. I(R = secondary alkyl) were best prepd. at room temp.- -40C; from the appropriate phosphorus ester. The mechanism of these reactions may involve a unimol. nucleophilic displacement. Reaction of (-)-(R)-di-2-octyl phenylphosphonate with I(R = H) did not provide direct support for the mechanism due to racemization of the product tosylate under exptl. conditions. I(R = H) with R1CO2CHMeCH2Me (R1 = Me, cyclohexyl) yielded I(R = CHMeCH2Me).

Then, from the same authors, there is also the transesterification of carboxylic acid esters with TsOH, however without checking the full paper it is unclear if the reaction can be used for preparative synthesis (I doubt it, from the abstract it looks more like they were studying the equilibrium and kinetics):

Reaction of carboxylic acid esters with p-toluenesulfonic acid.
Nitta, Yoshihiro; Arakawa, Yasushi.
Chemical & Pharmaceutical Bulletin, 33 (1985) 1380-1386.

Abstract: RCO2R1 (R = MeCOCH2, PhCOCH2, Ph, cyclohexyl, Cl, CO2Et, EtO2CCH2, EtO2CCH:CH EtO2C(CH2)3, Me, Me3C, Me2CH, Pr, ClCH2, Cl2CH, Cl3C; R1 = Et, Bu, hexyl, octyl) and OC(OR1)2 (R1 = Et, Me, Ph; R12 = CH2CH2) reacted with excess 4-MeC6H4SO3H to give 4-MeC6H4SO3R1. The mechanism of the transesterification is discussed.

[Edited on 1/4/2008 by Nicodem]

Attachment: tosylation.rar (354kB)
This file has been downloaded 803 times

Tosylation of alcohols

moarsauce - 11-10-2013 at 06:39

Hello,

I want to know how to proceed to perform a tosylation of an alcohol. My idea is to substitute the -OH group. I got 4-toluenesulfonyl chloride, but I don't know which solvent to choose. Can I just use no solvent if my alcohol is liquid? What about if it is a solid alcohol?

Which quantity of tosyl chloride do I need?

Also, what base should I use? I've read pyridine, but, should any common base would work (like NaOH, K2CO3, etc.)?

Must I heat my flask, or just agitate it?

bfesser - 11-10-2013 at 07:51

Try doing some lit. research and a forum search before asking so many questions—especially ones which are so easily answered.

Dariusrussell - 11-10-2013 at 09:24

http://cssp.chemspider.com/Article.aspx?id=155
also references a specific procedure.

http://www.researchgate.net/post/How_can_I_tosylate_an_hinde...
This isn't real literature but contains plenty of information

Common bases can be used as long as it will not react with your alcohol.
Hope these help, but next time do some reading first.
Also, http://www.sciencemadness.org/talk/viewthread.php?tid=11004

WPK0129 - 11-10-2013 at 13:31

Ditto to the above, but consider this:

If you use your alcohol you're trying to tosylate as the solvent, you'll likely have a large excess of that alcohol. Could your desired (tosylated) product be attacked by that same alcohol to form an ether?

Even experienced chemists don't always know what conditions will work and what won't. Pro-tip: set up a bunch of mini-reactions all at the same time, each with slightly different conditions (i.e., a different solvent in each, or a different base in each; different temperature for each is tricky, but if you can, great). This will allow you to find the right conditions quickly. ...just don't change more than one variable as you go from reaction to reaction.

[Edited on 11-10-2013 by WPK0129]

smaerd - 11-10-2013 at 18:15

Totally depends on the substrate. Water can be used to form a large amount of tosylates. Sodium hydroxide is fine as well. Heat isn't always advantageous. There is a thread on here about the tosylation of methanol. If you could be more specific about your intentions then more help may be provided...

[Edited on 12-10-2013 by smaerd]