Antoncho
(Official Hive Translator)
03-16-03 11:51
No 417550
      Methyl tosylate: _finally_ , OTC!!!
(Rated as: excellent)
 Bookmark   

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 DMSs (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 [victors 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 theres 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, theres 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 beakers bottom, theres 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 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 theres 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 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 sepd, 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 shouldnt really matter what kind of Cu we use here.


Now comes the juiciest part. In the patent the exerpts from which youre 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 for 10mins


5. Chill, filter, rextallize


6. React w/methanol as described earlier.

7. Voila!wink





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

Anyone wants to try this?smile





Yours,

Antoncho


P.S. I rated this post of mine at HyperLab (Post 417284 (Antoncho: " : -, !!!", Russian HyperLab)), but Ill reset the rating after you rate this onesmilelaughblush
 
 
 
 
    bottleneck
(Hive Bee)
03-16-03 12:17
No 417556
      Hey Antoncho, why not obtain these esters by...  Bookmark   

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
(Hive Bee)
03-17-03 15:16
No 418068
      Well, having looked at some patents, I guess...  Bookmark   

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
(Official Hive Translator)
03-21-03 10:22
No 419743
      Time for a lil dreamin'....
(Rated as: good read)
 Bookmark   

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 didnt cut it: the foam-like aniline salt just floated on top. To SWIMs 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 nitritecrazy SWIM is pretty absent-mindedsmile 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 lets 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 SWIMs apartment. Meanwhile, it was already 11 pm in the evening and SWIMs wife and parents were preparing themselves for the nights sleeplaugh.

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 frown maybee 2mls total.

SWIM couldnt 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. SWIMll see if it solidifies in the fridge (mp supposed to bee circa 15 C). Chemexper lists benzenesulfonyl chloride as Toxic (yknow, that skull picture), although toluenesulfonyl chloride and methyl benzenesulfonate are listed as only corrosive (can anyone tell me whats 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, Im very much in need of your input smile[yeah, I always say that][hope you like it and so onsmile]


Antoncho
 
 
 
 
    Vitus_Verdegast
(Hive Bee)
03-21-03 11:42
No 419759
      WARNING!! VERY TOXIC!!  Bookmark   


. 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!!shocked


http://www.metafilter.com/comments.mefi/21638
 
 
 
 
    Vitus_Verdegast
(Hive Bee)
03-21-03 11:47
No 419763
      SO2 fumes  Bookmark   


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. ?


http://www.metafilter.com/comments.mefi/21638
 
 
 
 
    yellium
(I'm Yust a Typo)
03-23-03 15:23
No 420427
      I wuldn't worry about the toxicity of ...  Bookmark   

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
(Hive Addict)
09-03-03 23:22
No 457066
      general rxn schemes for sulfochloride synthesis
(Rated as: good read)
 Bookmark   


[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
(Hive Bee)
09-10-03 18:34
No 458188
      Some alkylations with alkyl tosylates, Pt. 1
(Rated as: excellent)
 Bookmark   

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 wink)


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: 42-43C).
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: 81-82C) 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 185-186C (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: 42-43C). 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.




The candle that burns twice as bright burns half as long
 
 
 
 
    Lego
(Hive Bee)
09-10-03 18:43
No 458190
      Some alkylations with alkyl tosylates, Pt. 2
(Rated as: excellent)
 Bookmark   

About the alkylation of phenols with p-toluensulfonic acid esters
Monatshefte fuer Chemie, 1951, 82, 588-593 (http://www.angelfire.lycos.com/scifi2/lego/journals/29.djvu)
Translated excerpt

[...]
We found that the best way to alkylate phenols is the reaction in aqeuous NaOH. The ester are more reactive than the halides: Higher alkyl-groups could be inserted fast and without difficulties. If higher alkyls (more than 12 C-atoms) were used a small amount of the corresponding alcohol was formed by saponification of the ester. The alcohol could easily be removed (e.g. recrystallization).
The alkylation with primary aliphatic mono- or polyalcohols made no problems, secondary alcohols gave lower yields. In case of cycloaliphatic alcohols the yield decreased to 20%. In both of these cases the smell of olefin was present.
[...]
The allylation led to polymerisation if the temperature was too high. p-Toluenesulfonicacid benzylester was very reactive and showed drastic side reactions, therefore we got in aqeous media only few benzylphenylether. In this single case the reaction of an absolute ethanolic soultion with sodium phenolat was advantagous.
[...]
Ortho oder para substituents increasing the acidity of phenols made the alkylation more difficult. In ortho position to the phenolic hydroxyl group even a methyl-group obstructs.

Table 1. Methylation and ethylation of phenolic hydroxy groups.
Ether Molar amout of phenol Molar amount of ester Concentration of NaOH Reaction temperature, C Yield in % Comments
Anisole 0.2 0.2 2 N 70-90 82.7 ---
Guaiacol 0.5 0.5 3 N 70-90 46.0 N2-atmosphere used, side product: 26& veratrole
Veratrole 0.2 0.4 2 N 70-90 75.4 N2-atmosphere used
Nerolin, 0.1 0.1 2 N 70-90 96.3 ---
p-Methoxyacetophenone 0.475 0.48 3 N 70-90 85.0 ---
o-Methoxybenzaldehyde 0.2 0.2 3 N 70-90 70.0 ---
Hydroquinone dimethylether, 1,4-dimethoxybenzene 0.2 0.4 2 N 70-90 77.8 N2-atmosphere used
Phenethole 0.2 0.2 3 N 95 78.7 ---
Nerolin Neu, ethyl-2-naphtyl ether 0.2 0.2 3 N 95 90.0 ---
Hydroquinon diethylether 0.2 0.4 3 N 95 85.0 N2-atmosphere used


Table 2. Alkylation of phenolic hydroxyl groups with p-toluene sulfonic acid esters of higher, poly- and substituted alcohols.
Product Molar amout of phenol Molar amount of ester Reaction temperature, C Yield, % Comments
n-Propylphenylether 0.2 0.2 115 78.0 ---
n-Butylphenylether 0.2 0.2 115 79.2 ---
iso-Amylphenylether 0.2 0.2 115 79.1 ---
n-Hexylphenylether 0.2 0.2 115 84.2 ---
n-Octylphenylether 0.1 0.1 115 83.0 ---
n-Dodecylphenylether 0.1 0.1 115 85.0 ---
n-Octadecylphenylether 0.1 0.1 115 66.0 ---
iso-Propylphenylether 0.2 0.2 60-80 55.5 ---
Cyclohexylphenylether 0.1 0.1 60-80 17.0 ---
1,2-Diphenoxyethan 0.2 0.1 105 84.0 aus Glycoldi-tosylate
1,6-Diphenoxyhexan 0.2 0.1 108 98.0 aus Hexandiol-(1,6)-di-tosylate
1-Methoxy-2-phenoxyethan 0.2 0.2 95 76.8 from 2-Methoxy-ethyl-tosylate
2-Chloroethylphenylether 0.2 0.2 110 81.0 ---


Table 3. Influence of substituents on methylation of phenolic hydroxy-groups
Product boiling point, C/mm Hg n20D melting point, C Yield, %
o-Nitroanisole 134/9 1.5616 --- 65.0
m-Nitroanisole 121-123/8 --- 38 94.2
p-Nitroanisole --- --- 52 85.0
Methyl-o-toylether 55.5/9.5 1.5183 --- 76.0
Methyl-m-toylether 56.5/9 1.5147 --- 86.0
Methyl-p-toylether 56.2/9 1.5132 --- 83.0
o-Chloroanisole 77-78/10 1.5451 --- 63.0
m-Chloroanisole 70/9 1.5365 --- 86.0
p-Chloroanisole 71,5/9 1.5351 --- 82.7


Table 4. Aklyation with p-toluenesulfonicacid esters without isolating the ester
Ether Molar amount of sulfonyl chloride Molar amount of alcohol Molar amount of NaOH Reaction temperature, C Reaction time, h Molar amount of phenol Molar amout of NaOH Temperature of alkylation, C Yield in % based on sulfonyl chlroide Yield in % based on phenol
Nerolin Neu 0.25 0.45 0.25 15 3 0.2 0.2 95 77 96
Propyl-phenyl 0.66 1 2.5 35 0.5 0.66 --- 115 74 74
iso-Butyl-kreysl- 0.66 1 2.5 35 0.5 0.66 --- 115 75 75
n-Butyl-phenyl 0.25 0.25 0.25 15 to 20 4 0.2 0.2 115 67 84
n-Butyl-phenyl 0.25 0.25 --- -5 to -2 4 0.2 0.45 95 46.2 57.7


Experimetal

Phenetol.
19 g (0,2 mol) phenol were dissolved in 65 ml 3N NaOH (0.2 mol NaOH), treated wtih 40 g ethyl-p-tosylate, stirred and heated to reflux for 1 h. 10 ml 6 N NaOH were added and heating was continued for further 0.5 h.
After cooling the upper organic layer was taken up in Et[2]O, the etheral solution washed with dilute NaOH and H2O and dried. After evaporation the product was distilled in vacuo.
Yield: 19.2 g phenylethylether (78.7%)

[...]

Allylphenylether.
0.2 mol allyl-tosylate, 0.2 mol phenol and 6 N NaOH were stirred, the reaction temperature increased to 45-60C without external heating. After completion of the reaction the reaction was cooled, extracted with Et2O and worked-up as usual.
Yield: 15.7 allylphenylether, 58.6%

[...]

Benzylphenylether.
4.8 g Na (0.2 mol) were dissolved in 100 ml EtOH and treated with 19 g freshly distilled anhydrous phenol (0.2 mol). To this alcoholic phenolate solution 52.4 benzyl-toylsate (0.2 mol) were added and this mixture was stirred for 2 h at 60-70C. After addition of H2O benzylphenylether precipitated, it was filtered, washed and dried.
Yield: 36.4 (98.8%)
Before adding H2O most of the EtOH could be evaporated.

Nerolin Neu.
To 47.5 g p-toluenesulfonyl chloride (0.25 mol) and 20 g EtOH (0.45 mol) 40 ml 25%NaOH were added at 15C and stirred at this temperature for 3 h. 29 g [beta]-naphthole (0.2 mol), 8 g NaOH (0.2 mol) and 10 ml H2O were added to get a ~4 N NaOH solution.
This mixture was heated on a boiling water bath, then 10 ml 6 N NaOH were added and heated for further 30 min. After cooling the formed crystals are filtrated, washed with dilute NaOH and H2O and dried.
Yield: 33.0 g [beta]-naphthylethylether, melting point 36. Yield: 96% (based on used [beta]-naphthol), 77% (based on p-toluensulfonyl chloride)
The other experiments of Table 4 were carried out as described.

n-Butylphenyl ether.
18.5 n-butanol (0.25 mol) and 40 g pyridine (0.5 mol) were stirred at -5C, treated with 47.5 g p-toluenesulfonyl chloride (0.25 mol) and stirred for 4 h at -5C to -2C.
19 g Phenol (0.2 mol), 32 ccm 6 N NaOH (0.2 mol) and 10 g NaOH (0.25 mol) and heated and stirred on a boiling waterbath. After adding further 10 ml NaOH and heating for a short time the reaction mixture is cooled, treated with H2O and HCl and extracted with Et2O. The organic phase is washed with HCl, NaOH and H2O and dried. After usual workup 17.3 g n-butylphenyl ehter with a boiling point of 88C/9.5 mm Hg and n20D: 1.4978 are obtained.
Yield: 57.7% (based on phenol), 46.2% (based on p-toluenesulfonyl chloride and butanol)


Conclusion

[...]
The preparation of ethers does not require the isolation of the sulfonicacid ester.



The candle that burns twice as bright burns half as long
 
 
 
 
    Lego
(Hive Bee)
09-10-03 18:50
No 458191
      Some alkylations with alkyl tosylates, Pt. 3
(Rated as: excellent)
 Bookmark   

Monatshefte fuer Chemie, 1951, 82, 594-599.djvu (http://www.angelfire.lycos.com/scifi2/lego/journals/30.djvu)
About the alkylation of alcohols, thioalcohols and thiophenols with p-toluenesulfonicacid esters.

[...]

Table 1. Preparation of dialkylethers with p-toluenesulfonicacid esters and sodium alcoholates in benzene
Ether Molar amount of alcohol Molar amout of ester Yield, %
Ethyl-n-octyl n-Octyl; 0.1 Ethyl; 0.1 40.3
n-Butyl-n-octyl n-Butyl; 0.1 n-Octyl; 0.1 52
n-Butyl-n-octyl n-Octyl; 0.1 n-Butyl; 0.1 59.5
Ethylbenzyl Benzyl; 0.2 Ethyl; 0.2 62


Table 2. Alkylation of thioalcohols and thiophenols with p-toluenesulfonicacid esters
Sulfide Used thioalcohol Molar amout Reaction time, h Reaction temperature, C Yield, % Comments
Ethyl-p-tolyl p-Thiocresol 0.1 0.5 97 76.0 91-92/9 mm; n20D: 1.5568
n-Butyl-p-tolyl p-Thiocresol 0.1 0.5 112 83.5 120-122/9 mm; n20D: 1.5408
n-Dodecyl-p-tolyl p-Thiocresol 0.1 0.75 114 83.2 Melting point: 31-31.5 C
Ethylen-bis-p-tolyl p-Thiocresol 0.2 3 114 95.0 Melting point: 80 C
n-Dodecyl-n-butyl n-Butyl 0.15 0.75 113 81.09 168-171/9 mm; n20D: 1.4648
n-Butyl-iso-propyl n-Butyl 0.2 4 60-80 75.0 78,5-79/61 mm; n20D: 1.4479
n-Butyl-iso-propyl iso-Propyl 0.2 4 60-80 92.5 78,5-79/61 mm; n20D: 1.4479

9 By-product: 13.3% Di-n-dodecylsulfid

n-Dodecyl-p-tolylsulfide.
13 p-thiocresol, 16 ml 6 N NaOH (0.1 mol) and 34 g n-dodecyl-tosylate (0.1 mol) were stirred on an oilbath at ~150C for 45 min and refluxed. After cooling H2O was added and the formed white product was recrystallized.
Yield: 24.3 g (83.2%).

[...]

n-Butyl-iso-propylsulfide
15.2 iso-Propylthioalcohol (0.2 mol) were dissolved in 32 ml 6N NaOH, treated with 46 g n-butyl-tosylate (0.2 mol) and heated on the waterbath for 4 h at 60-80C.
After usual workup and vaccum distillation 24.4 g n-butyl-iso-propylsulfid was obtained (92.5%). [...]
The other sulfides were prepared as described (see Table 2.)


Now the deluxe version: wink

J. Org. Chem., 1990, 55, 5639-5646.pdf
Selective functionalization of calix[4]arenes at the upper rim
No DOI found

Nomenclature overkill (short version: 2 phenolic hydroxy groups are methylated)
A suspension of calix[4]arene (2) (30.0 g, 70.7 mmol), potassium carbonate (anhydrous, 10.7 g, 77.4 mmol), and methyl tosylate (26.3 g, 141.4 mmol) was refluxed in CH3CN (500 mL) for 24 h. After evaporation of the solvent, the mixture was taken up in CH2Cl2 (500 mL) and washed with 1 N HCl (2 x 50 mL) and brine (50 mL). The organic layer was dried with MgS04, and the solvent was evaporated to afford 5 as a pure white solid yield 30.8 g (97%); mp >300 "C.


Lego's voice: Although the authors are sometimes a bit vague and has some problems with nomenclature this method is suited for clandestine purposes. No special equipment is needed, only standard chemicals are used, the reaction is carried out on a multigram scale and the product is sufficient pure.


Proposal for alkylation of hydroxyaldehydes:

Dissolve the hydroxaldehyde in EtOH (~750 ml/1 mol) containing an equal molar amount of KOH (56.10 g/mol) or NaOH (40.00 g/mol).
Add an equal molar amount of methyl tosylate (186.23 g/mol).
Reflux for 1.5-2 h.
Pour in H2O (~4 times).
Extract several times with Et2O (other nonpolar solvent will work, too).
Wash the organic phase two times with alkaline solution (e.g. 5% KOH in H2O).
Wash the organic phase with H2O.
Dry with Na2SO4 or MgSO4.
Evaporation of the solvent yields the alkylated product.
If the product is unpure distillation or recrystallization can bee used to purify the product.

For alkylation of polyhydroxybenzaldehydes (e.g. 2,5-dihydroxybenzaldehyde or 3,4,5-trihydroxybenzaldehyde) one have to use the double resp. triple amount of methyl tosylate and KOH/NaOH.
For 2,5-dihydroxybenzaldehyde an inert gas atmosphere (N2 or Ar) to prevent oxidation will increase the yield.

For alkylation with higher alkyls one have to change the molar weight of the alkylating agent (e.g. 200.256 g/mol for ethyl tosylate, 212.266 g/mol for allyl tosylate).


Please note: The german articles were sometimes unprecise, old nomenclature, measuring units and terminology were used. As this is a translation one has to doublecheck the article and the translation before using these procedures. It is the own responsibility of every bee and chemist.

The candle that burns twice as bright burns half as long
 
 
 
 
    yinga
(Hive Bee)
09-23-03 20:52
No 460592
      aminophenols?  Bookmark   

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
(Hive Addict)
09-25-03 05:06
No 460878
      OTC anilines  Bookmark   

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
(Chief Bee)
09-25-03 14:32
No 460972
      Para-Nitration with Bentonite Clay/Dilute HNO3
(Rated as: good read)
 Bookmark   

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) (../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
(Hive Addict)
09-28-03 17:05
No 461471
      additional info  Bookmark   

OTC anilines

1) para-aminobenzoic acid (PABA), ~$6 per 60g from vitamin shops, much cheaper from any chem supplier
    decarboxylation at 180C, 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
(Hive Addict)
09-30-03 16:23
No 461888
      parts of Tetrahedron; 59; 8; 2003; 1317 - 1326
(Rated as: excellent)
 Bookmark   

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 5C. 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, 5C 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 5-25C 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 10C 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 5C. 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 5C. 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 18C 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 0-5C, 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 < 5C. After stirring 20 min, SO2 gas (42 g) was bubbled in over 40 min keeping the mixture <7C. 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 0-5C. 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 96-97C. 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--