Author Topic: Methyl tosylate: _finally_ , OTC!!!  (Read 4947 times)

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Antoncho

  • Guest
Methyl tosylate: _finally_ , OTC!!!
« on: March 16, 2003, 11:51:00 AM »
Hey, guys.

Looks like our quest for OTC, cheap, effective and non-poisonous  methylating agents is coming close to an end.

This is methyl benzenesulfonate – substance similar to methyl tosylate, but w/out that extra methyl group on the ring. It is a solid at RT (no carcinogenic vapors to breathe with), has high reactivity similar to DMS’s (will easily methylate aldehydes and such) and, the best of all , it can bee made from OTC and next-to-OTC things in an easy, non-demanding fashion [victor’s smile]


The preparation consists of two steps. The 2nd one is well-known: benzenesulfonylchloride is reacted w/MeOH (preparation given for methyl tosylate):




190g finely ground tosyl chloride is combined w/150g MeOH and cooled to 0 C. To this mixture there’s added 115g 40% NaOH in such a way that the temp never rises above 8 C. Stirring is continued for ~10h. The mixtr is poured into ice/water, precipitated product is filtered and washed w/water until complete removal of alkali. Crude ether is melted (28 C), filtered and distilled at reduced pressure.





The 1st , and the crucial for this pathway step is synthesising that sulfonyl chloride. Usually it is prepared by reacting the arene of choice w/chlorosulfonic acid, which is a nasty and definitely not easily accessible for a kitchen bee chemical.

As it turns out, there’s a much better way. These sulfonylchlorides may bee made by diazotizing an aniline, reacting it w/conc. soln of SO2 (can bee made in situ from bisulfite) in HCl and decomposing the adduct w/a copper salt.

Ordinarily this rxn gives high yields only w/electron-poor rings – due to the low thermostability of electron-rich aryldiazonium salts, as they say. But as you will see later on, there are gimmicks which allow one to pull this rxn on electron-rich substrates with decent yields.

Beelow there are three procedures, each of them has certain advantages that can and should bee combined together to produce the absolutely easiest and optimal procedure.


1. From

Patent US3947512



200 Parts by weight of 1-amino-2-methyl-4-nitrobenzene were diazotized at 0 DEG - 5 DEG C with 400 parts by weight of 30% hydrochloric acid and 235 parts by weight of 40% sodium nitrite solution. The clarified diazo solution was allowed to run, with slight external cooling, below the surface of a mixture of 1300 parts by weight of 30% hydrochloric acid, 33 parts by weight of crystalline copper sulfate and 330 parts by weight of 40% sodium bisulfite lye, while adding at the same time further 330 parts by weight of 40% sodium bisulfite lye. After about 45 minutes, the sulfonic acid chloride that had separated was filtered off with suction, washed with 2000 parts by volume of cold water and dried. The 2-methyl-4-nitrobenzene-sulfonic acid chloride was obtained in a yield of 85% of the theory and was found to melt at 105 DEG - 106 DEG C.


Here we have the rxn performed in a homogenous solution (i.e., no need for vigorous stirring) and also it teaches us that the SO2 can bee produced in situ. BTW, one of the products mentioned in the above patent is naphtylsulfochloride, yield – 72%


The next one:

2. From “Methods of synthesis of organic reagents”, Dykhanov, Jijelaeva, Ryzhkova, v.26, p. 134-135.

Into a 0,5l beaker equipped w/a stirrer, thermometer and a addition funnel the end of which is placed 9-10cm above the beaker’s bottom, there’s placed 16.05g (0.15mole) toluidine (or anisidine) and 12g H2SO4 in 200mls water. The suspension is heated until full dissolution of the pptt, cooled to 0-20 Ñ and diazotized w/10.35g NaNO2 in 35mls water (introduced beelow the surface). After the end of diazotization the xtals must fully dissolve and the soln have pH ~2 and give positive test on HNO2 (iodine-starch paper). Otherwise add 2-5mls acid or NaNO2 soln.

Into 1l flask there’s placed 100mls sat. soln of SO2 in GAA (30-33%) , 30mls conc. HCl, 150-200mls benzene and 6,5 CuCl2 and the mixtr is stired until fine emulsion forms. The diazonium soln is added thereto, the mixtr is heated to 30-45 Ñ and helg at that temp until N2 evolution stops (toluidines: temp=30-40 C; times: ortho – 90mins, meta – 10mins, para – 35mins; anisidines – temp=40-45 C; times: ortho – 240mins, meta – 15mins, para  - 60mins).

The rxn is poured into 3x qtty water, the organic layer is sep’d, washed w/water until washes beecome neutral, dried for 3hrs over 15g CaCl2, benzene stripped, the residue distilled in vacuo.

Yields: toluidines: ortho – 65.5%, meta –74.7%, para –80.2%; anisidines – ortho – 39.5%, meta –40.4%, para  -37.7%).


A couple of comments on the above proc: first of all, the authors use sulfate diazonium salts motivating their choice w/the notion that diazonium sulfates are more temp. stable – which assumingly has positive impact on yields.

Then, they say that the actual catalyst in the rxn is CuCl, which is formed from CuCl2 and SO2. So it shouldn’t really matter what kind of Cu we use here.


Now comes the juiciest part. In the patent the exerpts from which you’re about to read, authors make electron-rich sulfonyl chlorides from anilines with really good yields. They achieve it by:

a)   Using a PTC (which, as they say, speeds up decomposition of diazonium/sulfurous adduct, which has a positive impact on the yield)
b)   What is really cool is that they OXIDIZE the post-reaction mixture. The sulfinic acid, which is the major side-product in this rxn, upon oxidation turns into the same sulfonyl chloride. Although they use chlorine as oxidant in the examples, they say that it may bee hydrogen peroxide as well – weird but true. In any case, it should bee possible to make chlorine in situ by adding CaOCl2.

3. From

Patent US4393211



EXAMPLE 1
Preparation of 2-chlorobenzenesulfochloride
To 100 g of cooled 36% strength by weight hydrochloric acid (=1 mole of HCl) were added first 32 g (about 0.25 mole) of 2-chloroaniline and then, in the course of 15 min at 0 DEG-5 DEG C., 76 g of a 25% strength by weight sodium nitrite solution (=0.28 mole of NaNO2). Thereafter, the diazonium salt solution obtained was stirred for 10 min at 0 DEG C., following which the excess nitrous acid was destroyed with a small amount of urea.
The diazonium salt solution was then brought into contact with a solution of 100 ml of 1,2-dichloroethane and 21 g (0.33 mole) of SO2 at 20 DEG C., using vigorous stirring. Thereafter, a concentrated aqueous solution of 0.625 g (3.7 millimoles) of copper-II chloride dihydrate was added to the mixture, and the batch was heated to 50 DEG C., with stirring, and kept at this temperature until no more nitrogen was liberated; this required 80 min.
Thereafter, 2.5 g (35 millimoles) of chlorine gas were passed into the mixture at 50 DEG C. After 5 minutes, the phases were separated and the organic phase was worked up in a conventional manner to give the required product. The yield of pure 2-chlorobenzenesulfochloride (boiling point 144 DEG-146 DEG C./21 mbar) was about 93%.
EXAMPLE 2
Preparation of 4-methoxybenzenesulfochloride
A diazonium salt solution, prepared similarly to Example 1 from p-anisidine, was brought into intimate contact with a solution of 100 ml of diethyl ketone and 21 g (0.33 mole) of SO2, and was then decomposed using 0.5 g of CuCl2.2H2 O and 1 g of tetrabutylammonium chloride at 40 DEG C. Further treatment with 4.5 g (63 millimoles) of Cl2 and subsequent conventional working up of the reaction mixture gave 4-methoxybenzenesulfochloride in 87% yield; melting point 43 DEG C.
 






To sum up all of the said above, the ideal procedure for the kitchen synth should look like this:


1. Diazotize anilinium sulfate.


2. Make SO2 soln with bisulfite/HCl

3. Mix the solutions, add CuSO4, heat for 10mins at 40 C.


4. Add calculated amt of CaOCl2, heat at 50 Ñ for 10mins


5. Chill, filter, rextallize


6. React w/methanol as described earlier.

7. Voila! ;)





So, bees….. Do you like it? Any suggestions? Constructive criticism?

Anyone wants to try this? :)





Yours,

Antoncho


P.S. I rated this post of mine at HyperLab (

Post 417284 (missing)

(Antoncho: "Ìåòèë òîçèëàò: íàêîíåö-òî, ÎÒÑ !!!", Russian HyperLab)
), but I’ll reset the rating after you rate this one :)  ;D  :-[

bottleneck

  • Guest
Hey Antoncho, why not obtain these esters by...
« Reply #1 on: March 16, 2003, 12:17:00 PM »
Hey Antoncho, why not obtain these esters by esterification of the sulfonic acids? Is there some hindrance to this?

Edit: Well, after I tried orgsyn which was down, I did a search of the Hive, and I guess you found a reference for this once yourself. That is indeed OTC.

By the way, what's that I read in that very same thread about thiocyanation not working?? It sounded so sincere about 2C-SCN!

bottleneck

  • Guest
Well, having looked at some patents, I guess...
« Reply #2 on: March 17, 2003, 03:16:00 PM »
Well, having looked at some patents, I guess esterfication of the pure sulfonic acid is a bit difficult to find, and the chloride is normally used instead.

Even if that turned out to be necessary, and not just patent-mangling what is the big need for sulfonates anyway? As mentioned by PolytheneSam and others

Patent GB646736

already provides that dimethyl sulfate can be easily replaced with sodium methyl sulfate and monomethyl sulfate, which as far as I know are not so poisonous as DMS.

Besides, this reaction appears to take place in aqueous solution, so one presumably doesn't need to isolate sodium methyl sulfate, but can just use a presumed excess.

Antoncho

  • Guest
Time for a lil dreamin'....
« Reply #3 on: March 21, 2003, 10:22:00 AM »
Here goes.


The following solutions were prepared beeforehand:

1. 21,3 g (150mmole) of really old (1979) anilinium sulfate + 12g sulfuric acid in 200mls hot water. When all dissolved, rapidly chilled under running water (xtallization once again). Put in ice-salt bath.
2. 100mls conc. HCl + ~50cm3 ice from freezer. When the temp inside falls to ~zero slowly add 18g NaHSO3. No bubbles will evolve as long as you do it carefully, but keep the soln well covered – it stinks like hell!
3. 18g NaHSO3 in minimal qtty cold water (~40-50mls). Put in fridge.
4. 10.3g NaNO2 in 35mls water in addition funnel, chilled thoroughly under running water.


The solution 1 was put under mechanical stirring and thereto was added from the funnel nitrite solution. The mech stirrer SWIM used didn’t cut it: the foam-like aniline salt just floated on top. To SWIM’s greates surprise, no visible dissolution occurred after the addition! So SWIM, figuring that, maybee, he accidentally put a 5g weight on his scales intead of 10g one when weighing the nitrite ::)  – SWIM is pretty absent-minded :)  – decided to add more NaNO2 soln. Very soon it turned out that the pH turned neutral so SWIM added more acid, then more nitrite, more acid etc until the solids almost totally dissolved, the rxn by then being dark-brown. No NO2 smell was EVER observed.

“OK, now let’s assume that whatever happened there, we still got our diazonium salt” – SWIM thought and proceeded on.

The stirrer was now put in 1liter kitchen jar with the HCl/SO2 soln. In there was added a teaspoonfull of CuCl2 – surprisingly, the soln turns green! (SWIM thought Cu++ would get reduced, but the green color went away only later and reappeared in the eventual end of the reaction.). Stirring was started and diazonium solution (which was previously kept in icebath) was poured into the funnel thru a piece of several times folded bandage (improvised filtering) and added into the soln of SO2 and HCl. While the addition was carried out, the solution 3 was added in several portions thru a syringe. STRONG SULFUROUS SMELL!!!

When all was added, the soln was quite cold and dirty yellow in color. No observable reaction was taking place at that temp. Now SWIM had a great problem: the literary sources said to heat the soln to 30-40 C. But it was evident that such an operation would generate some awfull smell in SWIM’s apartment. Meanwhile, it was already 11 pm in the evening and SWIM’s wife and parents were preparing themselves for the night’s sleep ;D .

So SWIM just untightly covered the jar and put it into the closet overnight. Emission of nitrogen was slow at RT, the mixtr looked like a soda bottle opened some hours bee4, gently fizzing when swirled.

In the morning the bottom of the jar was covered with dark drops that were swirled into one bulk and pulled out with a pipette/syringe.

Then the soln was heated to 50 C on waterbath which lead to precipitation of yet more liquid, estimated 4-5mls. Bleach pool was then carefully added until sulfurous smell was gone, and some more after that. This proved to bee a BAD IDEA since the qtty of the liquid at the bottom actually DECREASED. Moreover, CaSO4 pptated which made recovery of what was left at the bottom even less effective  :(  – maybee 2mls total.

SWIM couldn’t bring himself to xtract the solution although obviously it contained more product and who knows how much was dissolved in water.

Anyway, the weight of crude, unwashed and undried stuff was 16,5 g (roughly 62%). It is a dark-brown heavy liquid with pronounced lacrimogenic properties. SWIM’ll see if it solidifies in the fridge (mp supposed to bee circa 15 C). Chemexper lists benzenesulfonyl chloride as “Toxic” (y’know, that skull picture), although toluenesulfonyl chloride and methyl benzenesulfonate are listed as only ‘corrosive’ (can anyone tell me what’s so dangerous about PhSO2Cl?).





Now, what was learned:

1. Omit the stirring in BOTH the 1st and the 2nd stages of the experiment. During the 1st step NaNO2 should bee added in portions and hand-shaking instead
of stirring would bee desirable.
During the 2nd step simply combine the solutions – no exoterm will occur and no reaction either, as long as they are both cold.
These modification will make the whole procedure much more pleasant and easy, I shall say.

2. Slow decomposition of diazonium adduct is possible, although doing as advised in the patents will probably increase the yield.

3. DO NOT add CaOCl2.



What remains unclear:

1. Can anyone suggest WTF happened in the diazotization stage?

2. Can anyone advise SWIM how to quickly and mildly destroy SO2 (so as to make further work-up of postreaction mixtr a more tolerable xperience)

3. What are the dangers of working with benzenesulfonyl chloride?





Please answer, fellow bees, I’m very much in need of your input  :) [yeah, I always say that][hope you like it and so on :) ]


Antoncho

Vitus_Verdegast

  • Guest
WARNING!! VERY TOXIC!!
« Reply #4 on: March 21, 2003, 11:42:00 AM »

. What are the dangers of working with benzenesulfonyl chloride?




from

http://physchem.ox.ac.uk/MSDS/BE/benzenesulfonyl_chloride.html



Safety data for benzenesulfonyl chloride

--------------------------------------------------------------------------------

General
Synonyms: benzenesulphonyl chloride
Molecular formula: C6H5SO2Cl
CAS No: 98-09-9
EC No:
Physical data
Appearance: colourless oily liquid
Melting point: 15 C
Boiling point: 251 C
Vapour density: 6.0 (air = 1)
Vapour pressure:
Density (g cm-3): 1.38
Flash point:
Explosion limits:
Autoignition temperature:
Water solubility: negligible
 
Stability
Stable. Incompatible with water, strong oxidizing agents, strong bases, methyl formamide, dimethyl sulfoxide.
Toxicology
Toxic. May be fatal if swallowed, inhaled or absorbed through the skin. Corrosive - causes burns. Eye, skin and respiratory irritant. Readily absorbed through the skin. Chronic exposure may lead to liver damage.
Toxicity data
(The meaning of any abbreviations which appear in this section is given here.)
ORL-RAT LD50 1960 mg kg-1
IPR-RAT LD50 76 mg kg-1
IHL-RAT LC50 32 ppm/1h

Risk phrases
(The meaning of any risk phrases which appear in this section is given here.)


Transport information
Personal protection
Safety glasses, gloves, good ventilation.
Safety phrases
(The meaning of any safety phrases which appear in this section is given here.)


Please take necessary precautions Antoncho!! :o




Vitus_Verdegast

  • Guest
SO2 fumes
« Reply #5 on: March 21, 2003, 11:47:00 AM »

2. Can anyone advise SWIM how to quickly and mildly destroy SO2 (so as to make further work-up of postreaction mixtr a more tolerable xperience)




Let fumes go through washing bottle w/ NaOH-sol. ?




yellium

  • Guest
I wuldn't worry about the toxicity of ...
« Reply #6 on: March 23, 2003, 03:23:00 PM »
I wuldn't worry about the toxicity of benzenesulfonyl chloride. If it's as reactive as chlorosulfonic acid, it's sensitivity to water can be much more dangerous.

psyloxy

  • Guest
general rxn schemes for sulfochloride synthesis
« Reply #7 on: September 03, 2003, 11:22:00 PM »

[1,2] RSH + 3 X2 + 2 H2O __> RSO2X + 5 HX

[2] RSSR + 5 X2 + 4 H2O __> 2 RSO2X + 8 HX

[3] R3Al __ +SO2 __> (R-SO-O)3Al __ +Cl2 __> RSO2Cl + AlCl3

          NH2                               NH2
         /                                 /
[4] RS-C(+) + 3 Cl2 + 2 H2O __> RSO2Cl + ClC(+) + 4 HCl _H2O_> CO2 + 2 (NH4+ + Cl-)
         \                                 \
          NH2                                NH2                     


[1]Duglass, I.B.; Johnson, T.B.: J. Amer. chem. Soc. 60 (1938) page 1486
[2]Duglass, I.B.; Farah, B.S.; Thomas, E.C.: J. org. Chemistry 26 (1961) page 1996
[3]

Patent US3134809

(1964)
[4]Johnson, T.B.; Sprague, J.M.: J. Amer. chem. Soc. 58 (1936) page 1348
   Sprague, J.M.; Johnson, T.B.: J. Amer. chem. Soc. 59 (1937) page 1837


--psyloxy--


Lego

  • Guest
Some alkylations with alkyl tosylates, Pt. 1
« Reply #8 on: September 10, 2003, 06:34:00 PM »
Methyl p-toluenesulfonate is not as harmless as dimethylcarbonate but definitive less toxic than dimethylsulfate or methyl iodide. Depending on the chemical company selling it methyl p-toluenesulfonate is either rated as irritating or 'may cause cancer'. Bees handling it should wear proper protecting clothes and handle this stuff with care.

As it can bee prepared OTC it offers an alternative to DMS and MeI but as far as TFSE told there is no working instruction or write-up in the Hive or at Rhodium's page.

Here are some practical applications (some are quite old but so nobee has to bee afraid that the authors clean their product via column chromatography  ;) )


Methylation of hydroxy aldehydes

Arch. Pharm., 1933, 271, 462-466

(http://www.angelfire.lycos.com/scifi2/lego/journals/28.djvu)
Translated excerpt

[...]

The reaction products (alkylated aldehyde and unreacted hydroxy aldehyde) are so pure that further purification (recrystallization or distillation) is only necessary in a few cases.

Dihydroxaldehydes can alkylated in this way, too. Yields are not as high because the formation of mono-alkylated and oxidized products.

Lacking enough starting material we were not able to develop a general method but there is no doubt that this method can be used with sucess for the alkylation of dihyroxy and polyhydroxyaldehydes.

[...]

Veratric aldehyde, 3-4-dimethoxybenzaldehyde
To 15.2 g vanillin (0.1 mol) a calculated amount of kalihydrat (probably KOH) was added and dissolved in 75 ml MeOH. 18 g methyl tosylate (0.1 mol) and heated on a water bath for 1.5 h to reflux. As soon as the the light yellow, clear solution starts boiling the potassium salt of methyl toluenesulfonic acid starts to precipitate. After 1.5 h everything is poured in about 300 ml of H2O. First there is a white emulsion which starts to separate a light yellow oil. The aqeuous solution and the oil is extracted exhaustive with Et2O, the organic phase is washed twice with 10 ml 5% aqeuous KOH to remove unreacted vanillin. The organic phase turns almost colourless, the alkaline solution is light yellow. The organic phase is washed with H2O, dried with freshly sulphate (probably MgSO4 or Na2SO4) and evaporated. The oily residue solidifies on cooling (melting point: 42-43°C).
Recrystallization from Et2O yields a white product. Yield: 13.8 g, 83% of theory.
The pooled basic solutions and wash water is acidified with 20% H2SO4 and extracted with Et2O. The organic phases are dried with Na2SO4 and treated as usally.
The yield of light yellow coloured vanillin (melting point: 81-82°C) is 2.5 g (increasing the yield to 99%) and it can be used without further purification.


Vanillin ethyl ether, 4-ethoxy-3-methoxybenzaldehyde
5 g vanillin were treated with 150 ml EtOH containing 2 g 90% KOH. 6.6 g ethyl toluenesulfonic acid are added and the reaction mixture is refluxed for 1.5 h. The still hot solution is poured in 600 ml H2O and proceeds as describe above.
Yield of ethyl vanillin (this must be an error, ethyl vanillin is 3-ethoxy-4-hydroxybenzaldehyde, the probably mean ethylated vanillin): 4.9 g. 0.9 g vanillin are recovered. Total yield: almost 99%.


Amyl ether of vanillin, 4-pentoxy-3-methoxybenzaldehyde
5 g vanillin are dissolved in 50 ml EtOH containing 2 g KOH (90%), then treated with 8 g amyl toluenesulfonic acid and refluxed for 2 h. The reaction mixture is poured in the 4-times amout of H2O and a heavy oil precipitates. The mixture is extracted with Et2O, the organic phase is washed two times with 5% alkali solution (any basic solution will work, not specified here), then with H2O and dried with Na2SO4. After evaporation a light yellow oil is obtained. After rectification one gets 5 g of a water-coloured (boiling point 185-186°C (17 mm)).
1 g vanilin was recovered from the wash water and alkaline solutions.
Total yield: 86%.


o-Methxoybenzaldehyde
12.2 g Salicylaldehyde (0.1 mol) are dissolved in 100 ml ethanolic KOH-solution, the solutions turns slightly green, 18.6 methyl toluenesulfonic acid are added and the solution is refluxed for 1.5 h.
The reaction after usual workup yields 10.5 o-methoxybenzaldehyde and 2.7 g salicylaldehyde.
Total yield: ~87%.


o-Ethxoybenzaldehyde
The reaction is carried out as above but with ethyl toluenesulfonic acid. From 12.2 g salicylaldehyde 2.5 g are recovered. 11.5 g of ethoxy compound are obtained. Total yield: ~96%.


4-Methoxybenzaldehyde
6.1 g p-Hydroxybenzaldehyde are dissolved in 50 ml of n-ethanolic potash lye, treated with 9.3 g methyl toluenesulfonic acid and heated to reflux on the water bath. After usual workup one gets 4.1 anisaldehyde. 2 g p-hydroxybenzaldehyde are recovered. Total yield: 90%.


Veratric aldehyde from protocatechualdehyde, 3,4-dimethoxybenzaldehyde from 3,4-dihydroxybenzaldehyde
5 g protocatechualdehyde are dissolved in 72 ml n-ethanolic potash lye, turning the solution instantly greenish-brown. 13.6 g methyl toluenesulfonic acid are added and the mixture is refluxed for 1.5 h on the water bath.
After usual workup one gets 3.5 g veratric aldehyde (melting point: 42-43°C). Yield: ~60%.
The ethanolic washing solutions after acidifying and extraction with Et2O yielded 2 g of dark crystalline product which is a mixture of the starting material and the monomethyl ester (probably the monomethylated product is meant).
Due to the lack of starting material and the difficulty of separating such mixtures we were not able to dertemine the quantitative relation.





yinga

  • Guest
aminophenols?
« Reply #9 on: September 23, 2003, 08:52:00 PM »
What would happen if this reaction (Antoncho's diazotization and etc.) was tried on an aminophenol?  I guess as the sulfonic acid chloride is developed it will tosylate the hydroxyl forming a useless polymer.  Unfortunately the only OTC aniline I know of is also a phenol.  Any ideas or other OTC anilines?

psyloxy

  • Guest
OTC anilines
« Reply #10 on: September 25, 2003, 05:06:00 AM »
Selective toluene para nitration[1]:
Yield         81%
Reagents      bentonite clay, aq. HNO3   
Solvent       hexane   
Time          5 hour(s)   
Other         Heating



Other nitration rxns give mixtures of isomeres, mostly ortho.

The 4-nitrotoluene is subsequenttly reduced to 4-methylaniline. For this type of reaction there's 100's of high yield variations out there, don't know what the latest trend is around here.

[1]Bahulayan, Damodaran; Narayan, Gopinathan; Sreekumar, Vellalath; Lalithambika, Malathy; SYNCAV; Synth.Commun.; EN; 32; 23; 2002; 3565 - 3574.


Rhodium

  • Guest
Para-Nitration with Bentonite Clay/Dilute HNO3
« Reply #11 on: September 25, 2003, 02:32:00 PM »
Natural Bentonite Clay/Dilute HNO3 (40%)
A Mild, Efficient, and Reusable Catalyst/Reagent System for Selective Mono Nitration and Benzylic Oxidations

Bahulayan, Damodaran; Narayan, Gopinathan; Sreekumar, Vellalath; Lalithambika, Malathy

Synth.Commun. 32(23), 3565-3574 (2002)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/para-nitration.bentonite-hno3.pdf)

Abstract

Selective mono nitration of Aromatic hydrocarbons and benzylic oxidations can be achieved in high yield using reusable catalyst/reagent system consisting of bentonite clay and dilute HNO3 under relatively mild experimental conditions. The dual behavior of the catalyst reagent system is utilized for the regioselective synthesis of a variety of industrially important compounds.

psyloxy

  • Guest
additional info
« Reply #12 on: September 28, 2003, 05:05:00 PM »
OTC anilines

1) para-aminobenzoic acid (PABA), ~$6 per 60g from vitamin shops, much cheaper from any chem supplier
    decarboxylation at 180°C, methylamine.carbonate as byproduct[1,2,3]

2) acetanilide (N-acetylaniline) - innocent material?, ~50$/Kg from chem supplier - hydrolysis gives aniline[4].

tosyl iodide

sodium tosylate and I2 will give tosyliodide in 100% yield[5]. Yeah, I know I2 is watched in th US and pricey. But it could be an alternative for a rich and lazy european.

[1] Weith; CHBEAM; Chem.Ber.; 12; 1879; 103.
[2] Meisenheimer; v. Budkewicz; Kananow; JLACBF; Justus Liebigs Ann. Chem.; 423; 1921; 90, 91.
[3] McMaster; Shriner; JACSAT; J.Amer.Chem.Soc.; 45; 1923; 752.
[4] Aman, Ahmed M.; Brown, R. S.; JACSAT; J.Amer.Chem.Soc.; EN; 121; 19; 1999; 4598 - 4607.
[5] Oae, Shigeru; Togo, Hideo; BCSJA8; Bull.Chem.Soc.Jpn.; EN; 56; 12; 1983; 3813-3817.
--psyloxy

psyloxy

  • Guest
parts of Tetrahedron; 59; 8; 2003; 1317 - 1326
« Reply #13 on: September 30, 2003, 04:23:00 PM »
The most recent covering of that topic in the literature:
Conversion of anilines to sulfonyl chlorides via their diazonium salts is a known but little used reaction. The diazonium salt is allowed to react with sulfur dioxide and HCl in the presence of copper(I) or (II) salts to afford the sulfonyl chloride directly. This process was attractive because it offered one-pot access to our desired sulfonyl chloride 3 with complete regiochemical control starting from the readily available 15 (Scheme 7).
Scheme 7:
cmpd. 15 is 4-[4-(-4-Triflouromethyl-phenyl)-thiazol-2-yl]-phenylamine hydrobromide

cmpds 3,20,21 and 18 result from substitution of the -NH2 in 15 with R.

3 : R=SO2Cl
18: R=SO3H
20: R=SO2Br
21: R=Cl

Thus, treatment of the hydrobromide salt of aniline 15 with sodium nitrite in a mixture of glacial acetic acid and aqueous hydrochloric acid afforded the corresponding diazonium salt. Treatment of the resulting slurry with sulfur dioxide and copper salts afforded a mixture of sulfonyl halides 3 and 20, which crystallized directly from the reaction mixture. Some undesired aryl chloride 21 and bromide 14 (via a Sandmeyer reaction) as well as sulfonic acid 18 were also generated, but these were all removed in the crystallization.

Further optimization of these conditions was pursued to ensure that this process can be performed safely.

Diazotization of 15 occurs rapidly to afford a bright, yellow diazonium salt, much of which is out of solution. Thermal analyses of these solids showed their potential for extremely rapid, exothermic decomposition. In contrast, in solution, only slow and low energy decompositions were observed. Thus, a process was developed in which all of the diazonium salt remained in solution and in which the chlorosulfonylation reaction was executed at or below room temperature. The solubility of the diazonium salt in several water miscible organic solvents was found to decrease in the following order: DMF>THF, acetonitrile>acetone> dioxane. Further evaluation demonstrated that acetonitrile was the best solvent for our process.

For the chlorosulfonylation step, both copper(I) and copper(II) salts (chlorides, bromides, acetates and triflates) were effective in catalyzing the reaction with sulfur dioxide. With copper(I) salts the reaction was generally faster and more vigorous than with copper(II) salts. The latter were preferred since they allowed better control of temperature and foaming, which is caused by the liberation of nitrogen during this step. Aryl chloride 21 and sulfonic acid 18 are the principal side products in this reaction. Optimization studies showed that minimizing the amount of water and increasing the SO2 concentration reduces the formation of 18 and 21, respectively (Table 2).


Entry Equiv. SO2   Rxn time (h) 3vs21   3yield, A% purity
1      2.2         23            4/l      75%   94.9 A%
2     10.0          7           13/1      90%   97.8 A%
3     16.0          3           18/1      92%   98.2 A%
4     32.0          3           36/l      93%   99.1 A%



 The reaction rate, yield and purity of the product increased as more SO2 was used. On the other hand, it is also important to keep the excess of corrosive SO2 to a minimum. Thus, we arrived at an optimum charge of --20 equiv. Of SO2. The gas can be introduced by either adding a 30% solution in acetic acid (saturated) or by passing gaseous SO2 into the reaction mixture directly. On larger scale condensation of the gas can be conveniently achieved by introduction into a closed vessel at a pressure of 5 psig at 5°C. Emission of SO2 can be controlled by using a caustic scrubber in the venting lines of the reaction vessel and water for the bay scrubber.

Under optimum conditions, a mixture of 3 and 20 was produced in a 2.6:l ratio and 84% overall yield starting with the HBr salt of aniline 15, which was prepared from readily available bromoketone 6 (F3C-PhCOCH2Br). The use of a mixture of sulfonyl halides was inconsequential for the next step. Pure sulfonyl chloride could be prepared by using either the HCl salt of 15 (prepared from chloroketone 7) or its free base. Pure sulfonyl bromide 20 could be prepared by running the reaction with concentrated HBr instead of concentrated HCl. Detailed hazard evaluation showed that our optimum process was operationally safe. Subsequent reaction of aniline free base 15 on multi-kg scale afforded sulfonyl chloride 3 in a reproducible 90% overall yield and excellent purity.

Table 3. Diazotization: acetonitrile, acetic, HCl, 1.2 equiv. NaNO2, 5°C Chlorosulfonylation: 21-33 equiv. SO2, 1.26 equiv. CuCl2, RT age

Substrate       Product                   Yield
para-toluidine  toluenesulfonylchloride   99%
etc...

In an effort to demonstrate the scope of our newly developed diazotization/chlorosulfonylation procedure we examined five other anilines (Table 3). In each case, corresponding sulfonyl chloride was isolated in high yield and purity (>98%) after filtration of the crude reaction mixtures. Impurities were rejected to the acetonitrile-rich mother liquors and recrystallization of the products was not necessary. The procedure is most likely safe in these cases too since all diazonium salts were completely solubilized. In the case of aniline 28 some diazonium salt was out of solution. It is projected that some additional development on a case-by-case basis can circumvent this potential problem.

In conclusion the diazotization/chlorosulfonation reaction outlined above provides the most practical and economic approach to sulfonyl chloride 3. All operations are performed in the 5-25°C range, and inexpensive and readily available reagents are used. The desired product can be isolated directly from the crude reaction mixture via a simple filtration. Importantly, starting with regioisomerically pure aniline 15 guarantees the production of pure sulfonyl chloride 3. It should be noted that solubilization of the diazonium salt intermediate significantly reduces the potential hazard of working with this high-energy species. Indeed, this process has been safely scaled up to prepare multi-kg quantities of sulfonyl chloride 3 in high yield and purity.

4-[4-(-4-Triflouromethyl-phenyl)-thiazol-2-yl]-phenylsulfonylchloride.

From 15.HBr salt: the aniline hydrobromide salt 15 (50 g, 0.125 mol) was suspended in 500 mL of acetonitrile and cooled over an ice bath. Concentrated HCl (200 ml.) was added to afford a creamy mixture. A solution of NaNO2 (10.3 g, 0.150 mol) in 25 mL of water was added via an addition funnel over 10 min. The temperature rose to 10°C during the addition, and an HPLC assay after 25 min showed complete conversion to the diazonium salt. A 30 wt% saturated solution of SO2 in acetic acid (300 mL) was poured into the reaction mixture. Then, a solution of CuCl2*2H2O (10.6 g) in 25 mL of water was added. In a few minutes, the dark solution yielded thick brown precipitates. Over time, tan solids of the sulfonyl chloride formed. After stirring for 2.5 h these solids were filtered and rinsed 250 mL of acetic acid, 200 mL l:l mixture of acetic acid/water and 800 mL of water. The solids were dried to afford sulfonyl chloride 3 (44 g, 92.5% pure, 81% yield) as a light yellow solid. This product was a 72:28 mixture of sulfonyl chloride and sulfonyl bromide, as determined by titration.

From 15 free base: in a glass pressure vessel, aniline freebase 15 (16.04 g, 50 mmol) was dissolved in 400 mL of acetonitrile at room temperature, and 40 mL of acetic acid was added. Concentrated HCl (40 mL) was added slowly over 2 min to afford a thick slurry, which was cooled to 5°C. A solution of NaNO2 (4.14 g, 60 mmol) in 10 mL of water was added over 1 min, and the resulting solution was stirred for 20 min at 5°C. The vessel was pressurized over 35 min with SO2 gas (88.7 g, l.38 mol) from a cylinder to 5 psig, keeping the temperature at <10'C. Then, a solution of CuCl2.2H20 (8.52 g, 50 mmol) in 10 mL of water was added. The temperature was allowed to rise to 18°C over 10 min and the mixture was stirred for 4 h at room temperature. The slurry was filtered and rinsed sequentially with 50 mL of acetonitrile, 150 mL of water, and 50 mL of acetonitrile. The solids were vacuum dried overnight to afford sulfonyl chloride 3 (18.6 g, 99.5% pure, 91% yield).

4.2.15. 4-Benzoyl-benzenesulfonyl chloride (23) (representative procedure).

4-Aminobenzophenone 22 (3.94 g, 20.0 mmol) was dissolved in 160 mL of acetonitrile and after cooling to 0-5°C, 16 mL of acetic acid and 8 mL of concentrated HCl were added. To the mixture was added NaNO2 (l.66 g, in 3 mL water) over 10 min at < 5°C. After stirring 20 min, SO2 gas (42 g) was bubbled in over 40 min keeping the mixture <7°C. A solution of CuCl2 (3.4 g, 25 mmol) in water (3 mL) was added and the mixture was allowed to warm and stir for 16 h at room temperature. The mixture was concentrated to 80 mL and was cooled to 0-5°C. The solids were filtered, washed with 20 mL of water, and dried to afford sulfonyl chloride 23 (5.27 g, 94% yield) as a pink solid; mp 96-97°C. 1H NMR (400 MHz, CDCl3): S 7.55 (m, 2H), 7.66 (m, lH), 7.82 (m, 2H), 8.00 (m, 2H), 8.17 (m, 2H). 13C NMR (100 MHz, CDCl3): S 127.0, 128.7, 130.l, 130.7, 133.6, 136.0, 143.5, 146.6, 194.5. Anal. Calcd for C13H9ClO3S (280.73): C, 55.62; H, 3.23; Cl, 12.63; S, 11.42. Found: C, 55.55; H, 3.23; Cl, 12.54; S, 11.25.
4.2.14.

Full Ref:  Ikemoto, Norihiro; Liu, Jinchu; Brands, Karel M. J.; McNamara, James M.; Reider, Paul J.; TETRAB; Tetrahedron; EN; 59; 8; 2003; 1317 - 1326.

--psyloxy--