Author Topic: Synthesis of 2,5-dimethoxy-1-ethylbenzene  (Read 1804 times)

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scarmani

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Synthesis of 2,5-dimethoxy-1-ethylbenzene
« on: August 20, 2003, 05:55:00 AM »
Swim found the following information -- inscribed in invisible ink -- on a transparency concealed within an opaque fish-tank. 

After rinsing with toluene and brushing off all the deceased toucans, swim was able to read:


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"You can reduce 2,5-dimethoxyacetophenone to 2,5-dimethoxyethylbenzene with Zn/Hg and HCl in 50% yield too, see JOC 25, 1245 (1960)"

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Surprisingly, the text of that very reference constituted the next paragraph Swim read:

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"Mossy zinc (140g) was amalgamated by a standard procedure* and the amalgam refluxed with 263 mL of concd. hydrochloric acid and 175 mL of water while 35 g. of 2,5-dimethoxyacetophenone was added over a 1-hr perod.  Reflux was continued for 22h during which time 97 mL of additional concd. hydrocloric acid was added in 10-mL increments.  The oily upper layer was then separated, dried with calcium chloride and fractionated under reduced pressure.  The main fraction, b.p. 65-67.5°C/ 5mm, consisted of 15.7 g (49%) of a pale yellow liquid.  Refractionation gave a colorless analytical sample, b.p. 68-70°C/ 7mm, f.p. -4 to -6.5°C."

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Swim was tickled to find that the *'ed reference to standard zinc amalgamation was the next item quoted on the transparency:

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"The procedure originally used by Clemmensen is satisfactory for the reduction of many carbonyl compounds which are appreciably soluble in the acid mixture, or which melt below the boiling point of the reaction.  The exact proportions of zinc and hydrochloric acid employed are not of great importance provided that both are present in large excess... 

The use of mechanical stirring has been reported, but in most cases sufficient agitation is provided by the ebullition of the hot acid.

The physical form of the zinc appears not to be critical, since zinc turnings, zinc wool, granulated zinc, zinc powder, and mossy zinc have given good results.  Mossy zinc has been most commonly used...

The zinc is ordinarily amalgamated by treatement with 5% - 10% weight of mercuric chloride in the form of a 5 - 10% aqueous solution.  The time required for amalgamation can be diminished by employing a solution of mercuric chloride in very dilute hydrochloric acid.  In order to obtain a homogenous amalgam, it is advisible to shake or stir the mixture during tha amalgamation.

Preparation of Zinc Amalgam:  A mixture of 100g mossy zinc, 5 to 10 g. of mercuric chlorie, 5 cc. concentrated hydrochloric acid and 100 to 150 cc. of water is stirred for five minutes.  The aqueous solution is decanted, and the amalgamated zinc is covered with 75cc of water and 100cc of concentrated hydrocloric acid.  The material to be reduced, [usually about 40g], is then added immediately and the reaction is started."

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a brief additional reference to 2,5-dimethoxy-1-ethylbenzene was included:

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"A pale straw colored liquid was distilled at 120°-140°C at the water pump to give 2,5-dimethoxy-1-ethylbenzene as a white fluid product."

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This confirmed the description of a white fluid, but did not give much insight into the pressure at which the boiling point was measured.

It was here that the transparent text launched into a puzzling continuation, which piqued my interest.  It did not appear to be a reference to published material:


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"140 g mossy zinc -- [aside: mossy zinc == jagged, solid, bitesized nuggets of zinc, as though molten metal drops had been gleefully splattered onto a cold irregular surface] -- was weighed out and placed into a large three necked roundbottomed flask equipped with overhead stirrer, addition funnel & reflux condensor.  175 mL of water was measured and poured in with the zinc.

7 g of mercuric chloride was cautiously weighed out and tapped into the roundbottomed flask.  7 mL of concentrated hydrochloric acid was measured and poured into the roundbottommed flask.

The various apparatii (addition funnel, reflux condenser, stirrer shaft / adapter) were placed securely in the necks of the roundbottomed flask and stirring was initiated immediately, and continued for five minutes.  The zinc turned dull grey, followed by an identical color change in the water (with slight fizzing observed), and subsequently bright patches of exposed elemental zinc could be seen.

After five minutes, the aqueous solution was decanted into an appropriate waste receptacle.  The amalgamated zinc was retained in the roundbottom, which had become warm to the touch.

To this approximately 140g of amalgamated zinc, was added 175 mL of water and then, gradually, 263 mL of conc. hydrochloric acid.  Moderate amounts of heat and bubbling hydrogen gas were generated during the addition of the hydrochloric acid. 

Once all the hydrochloric acid had been added through the addition funnel, stirring and heating were started.  After about 20 minutes, reflux had been established

At this point, 35 g. of pale yellow, pungent 2,5-dimethoxyacetophenone was measured out and added to the addition funnel.  While placing the 2,5-dimethoxyacetophenone in the addition funnel, it was observed that Residual traces of concentrated hydrochloric acid on the addition funnel caused the initial few droplets of the acetophenone to rapidly darken to an orange-brown color.  Most of the acetophenone was unaffected.

The addition funnel stopcock was adjusted so that the acetophenone dripped out at the rate of about a drop every two seconds into the refluxing reaction mixture...(introduced to the reaction mixture dropwise over the course of 1 hour.)

Once the addition of acetophenone was complete, reflux was continued for an additional 22 hours.  At two hour intervals, 10mL of concentrated HCl was added.

During the course of the reaction, the aqueous layer progressed from pale gray to dark brown and finally to a clear, dim bluish color [?].  It is surmised that the unfortunate use of a stainless steel stirring rod (which was corroded by the HCl liquid & fumes) was responsible for the brown / blue discolorations of the aqueous phase.

Throughout the course of the reaction, the added acetophenone was an oily upper layer... initially pale yellow, gradually becoming a water-white, oily fluid, and then in the last several hours, increasingly brown and viscous oil that began to coat the sides of the roundbottom.  It was hypothesized that the clear white oil observed in the middle stretch of the reaction was mostly desired product, and the viscous brown material that developed towards the end consisted of unwanted products of polymerizations and side reactions from prolonged reflux.

After 22 hours, the reflux was stopped and the aqueous layer was decanted into a separatory funnel.

There was some residual zinc amalgam remaining in the flask's round bottom.  It was cautiously rinsed out and disposed of in the same waste container as previous mercury-containing waste.

The separatory funnel now contained: lower dim blue aqueous layer, and and upper, viscous brown oily layer of about 35mL volume, which clung to the glass sides of containers it was in, and broke into rubbery droplets when agitated in water.

The viscous brown oil was fully separated but not washed or dried.  It was left to sit in the dark at room temperature in a sealed container for about a day.

The brown oil was then placed in a small round-bottomed flask.  A vacuum distillation setup was assembled with an oil-bath as the heat source & a jacketed condensor leading to another small round-bottomed recieving flask.

A vacuum of 1.8 - 2.0 mm Hg (measured in the Vacuum Line, NOT inside the distillation apparatus) was established. (i.e., a vacuum of 1800 to 2000 microns, which was the highest pressure that could be measured with available equipment) and immediately there was bumping of the crude product, probably due to the absense of boiling chips & presence of residual water (since product had not been dried).

The bumping was not severe enough to be problematic, and after several minutes of vacuum, subsided.  There was no appreciable decrease in the volume of the crude product.

After consultation of a nomograph plus calculation of theoretical b.p. using Clausius / Cla-pey-ron equation, it was expected that the b.p. of desired product would be about 45°C at 2mm Hg.

With this in mind, the temperature of the oilbath was raised gradually.  As minutes passed, the oilbath temperature rose through 30°C, then 40°C and 50°C without any discernable activity in the distillation flask.

Finally, with the oilbath temperature above 60°C, sporadic bumping / bubbling was once again observed in the brown oily crude product.

It became apparent that the size of the distillation setup was too large for the modest amount of liquid being distilled, since despite the occasional bump, no liquid was seen condensing in the condenser, (and very little even on the sides of the roundbottom distilling flask.)

Also of concern was the oilbath's high temperature relative to the calculated theoretical boiling point of the desired product at the measured pressure (65 to 70°C oil vs. about 45° expected distillation temperature).  Due to such concern, the oil temperature was maintained at no more than 70°C, to avoid potential severe bumping.

However, with only sporadic bloops in the distillation flask, no significant vapor was being produced and no progress was made in vacuum distillation.  Eventually distillation was terminated and plans were made to alter the setup to better conform to the small scale of distillation being performed.

A mini-scale vacuum distillation setup was assembled, which used a two-necked, standard joint "test tube" as the distillation flask and a small roundbottom as the recieving flask.  The crude product was placed in the test tube, attached to which was a thermometer/inlet adapter,  and a three-way distillation adapter.  The distillation adapter was connected directly to the receiving flask, without a jacketed condenser intervening. Although no boiling stones were available, a small stirbar was included in the distillation vessel and the oilbath was also stirred magnetically using a stirrer/hotplate.

This time, the oilbath was heated more agressively and the vacuum was strengthened to 0.4 mm Hg (400 microns) - again, measured in the vacuum line, not within the distillation apparatus.  The oilbath again reached a temperature of about 60°C before any activity was observed in the distillation "flask".  Again, the crude product began bumping despite the stirbar.  Nevertheless, heating of the oilbath continued and the temperature of the distilling vapor was monitored.  Once the oilbath had reached a temperature of about 80°C, the rate of bumping increased and a pale/clear, low-viscosity oily fluid began condensing on the side of the distillation "flask" (test-tube) and also on the thermometer bulb.  ...the thermometer inside the distillation container shot up to 65°C.

As the oilbath temperature was increased to 100°C, enough vapor was generated that pale/clear oil began condensing in the distillation adaptor and dripping into the recieving flask.  The temperature of the distilling vapor remained steady at 65°C but the rate of distillation increased as the oilbath temperature was raised.

The attainment of successful vaccuum distillation was heartening, but the unexpectedly high temperature of the distilling product was disheartening.  Although the references suggested a boiling point of about 65°C, it was at a pressure of 5mm, not at 0.5mm.  Equations were double-checked, but consistently it was calculated that the boiling point of the expected product, 2,5-dimethoxy-1-ethylbenzene, should have been much lower at the pressure of 0.4 mm Hg.

Nevertheless, all other aspects of the distilling substance matched description, and distillation was continued over the course of about an hour, yeilding about 10mL of clear/pale oil in the recieving flask and about 25mL of extremely viscous, tacky black muck in the distillation vessel (similar to taffy / cool tar in consistency).

It is of concern that the 10mL of pale oil obtained is not the desired 2,5-dimethoxy-1-ethylbenzene, although in most respects it matches descriptions of the substance... the boiling point of the liquid at low pressure does not correspond to the calculated boiling point."

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Here, Swim abruptly encountered the lower edge of the transparency.

After reading through all that verbigarbage, I felt a sense of cameraderie and empathy for the unknown author, and took a few minutes to scribble out my own calculations of the boiling point of 2,5-dimethoxy-1-ethylbenzene

The most accurate data point provided in the references was "68°C to 70°C at 7mm Hg."

The Clausius Cla-pey-ron equation for calculating phase transition to gas is given as


p = p° exp ( (-deltaH / R) * (1/T - 1/T°) )

substituting knowns and assuming the heat of vaporisation for 2,5-dimethoxy-ethylbenzene is ~50 [J/mol-°K], this yields

0.4 torr = 7 torr *  e ^ { (-50/8.314)[ J/mol-°K ] * (1/ (273+69)°K - (1 / ???)°K) }

From this calculation, Swim gets an expected boiling point of around 33°C at 0.4 mm Hg.  This does not match very well with the author's reported distillation temperature of 65°C to 70°C at 0.4 mm Hg.

Thus, Swim also wonders if the mysterious author of the transparent saga is justified in his concern about the identity of the product.

Swim notices that the author is measuring his vacuum outside the vacuum apparatus, AFTER the distilling vapor has been condensed.  Swim wonders if the pressure conditions INSIDE the distillation flask may have been different -- the pressure higher due to vapor of the distilling crude product.

It makes sense that the pressure should drop after the vapor is condensed at low temperature in the recieving flask.  Thus, the measured pressure in the vacuum line could be lower than the actual pressure experienced by the distilling substances, perhaps explaining the higher than expected boiling point?

As a last note: it occurs to Swim that the f.p. of 2,5-dimethoxy-1-ethylbenzene was provided in one of the references (-4 to -7 °C), but that the author of the bizzarre, concealed transparency made no mention of checking the f.p. of his unknown product.

Swim thinks that perhaps this is the next thing the author should try, if he hasn't already done so.

What do y'all think?



scarmani

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Discrepant F.P -- Definitely Wrong Product?
« Reply #1 on: August 21, 2003, 10:47:00 AM »
After examining the opaque fishtank more carefully, Swim found a second transparency hidden amongst the rushes!!!  Peering at it by the guttering light of a grim vivisectionists' lantern, Swim was barely able to make out some words...  as it turns out, the author of the transparencies has done a crude F.P. test:

"Pale colorless oil obtained by vacuum distillation was placed in a test tube, which was lowered into an icewater / calcium chloride bath (measured temperature of bath = -15°C).

After 30 minutes in the test tube, no crystalization or solidification of oil had been observed.  It was concluded that the pale oil did not have an F.P. of between -4°C to -8°C and thus could not have been the desired product, 2,5-dimethoxy-ethylbenzene."

Golly Gee Willikers.  Swim hates to say it, but it looks like the mysterious author's creeping suspicions have lept up violently with Ginsu knives and confirmed themselves.

Swim has a feeling the mysterious author might attempt a rerun of the zinc amalgam / long reflux.  He wishes that he could help the author.  Swim wonders if others have Any ideas?


scarmani

  • Guest
Consistent Results
« Reply #2 on: September 11, 2003, 03:47:00 AM »
Swim was - unsurprisingly - unsurprised when he stared at the laser and watched the boats go by in the summer to see how it works with the tentacles.  Needless to say, the bottle contained a message which specified:

"A reassay of the zinc amalgam reduction of 2,5-dimethoxyacetophenone to 2,5-dimethoxy-1-ethylbenzene was completed, minus the difficulties that had plagued the virgin run.  An acid-compatible stirring apparatus was utilized.  Heat input was stable and controlled in a manner that maximized the 'steady ebullition' to 'tar generation' ratio.  In short, the procedure was completed without notable malfunction.

The dark oil was separated and fractionated under ~1mm Hg with a 300 mm Vigreux column, attached to a Liebig condenser and thence, by two way adapter, to recieving flask in one neck, and bleed-in capillary in the second.

In the distillation flask, there had been placed some considerable quantity of shredded teflon tape, as it was hoped that this would moderate problems with bumping.

There was immediate violent bumping upon application of the vacuum.  It was conjectured that this was caused by residual water in the product, as said product had not been dried. 

After several minutes, the bumping subsided.  Heat was then gradually applied, and over the course of a few dozen minutes, the severe bumping was reinitiated, and the condensing ring of vapor coaxed up the vigreux column.  At the juncture of the vigreux column and liebig condenser, a thermometer which had theretofore been reading 30°C rose to 40°C, and settled at 40°C for a few minutes.  However, the very severe and sporadic bumping caused the temperature reading to surge above 40°C and then return.  Since the theoretical boiling point of the 2,5-dimethoxy-1-ethylbenzene at ~1mm reduced pressure was calculated as 30°C to 40°C, it was hoped that the surges in measured temperature were due to superheated vapor and did not reflect the boiling point of the distillate itself.

However, as condensate began collecting in the recieving flask in earnest, the thermometer hit 65°C and sat there for the remaining three hours of fractionation.

The pale straw-yellow oil fraction obtained matched all visual descriptions of 2,5-dimethoxy-1-ethylbenzene but failed to have the theoretically calculated boiling point.  Since the boiling points of products from both synthetic attempts were identical, and they differed from the boiling point of the starting product, it is hoped that the obtained product is indeed 2,5-dimethoxy-1-ethylbenzene, and that for some reason the observed boiling point differs from the theoretical.


Rhodium

  • Guest
1-Ethyl-2,5-dimethoxybenzene Synthesis
« Reply #3 on: September 12, 2003, 04:10:00 AM »
I must thank you for writing the very interesting posts above, even if I haven't replied before, but until now I have been unable to really help you with any hard facts. Below I have however pasted two complete preparations of 2,5-dimethoxyethylbenzene from the literature (one which you have already quoted from), complete with some physical properties. I hope it will be of use to you at this point.

Never use calculated boiling points for identification purposes, as nomographs and the like seldom are very reliable.
If all properties of a substance makes sense, except a calculated bp, then do not assume that the substance isn't what you hope it is, blame the bp - such properties can only be determined experimentally (just like a melting point).



1-Ethyl-2,5-dimethoxybenzene
J. Org. Chem. 25, 1245-1247 (1960)

Mossy zinc (140 g) was amalgamated by a standard procedure11 and the amalgam refluxed with 263 mL of conc. hydrochloric acid and 175 mL of water while 35g of 2,5-dimethoxyacetophenone was added over a one hour period. Reflux was continued for 22 h, during which time 97 mL of additional conc hydrochloric acid was added in 10-mL increments. The oily upper layer was then separated, dried with calcium chloride and fractionated under reduced pressure. The main fraction, bp 65-67.5°C/5mmHg, consisted of 15.7 g (49%) of a pale yellow liquid. Refractionation gave a colorless analytical sample, bp 68-70°C/7mmHg, mp -4°C to -6.5°C.

1-Ethyl-2,5-dimethoxybenzene
J. Org. Chem. 52, 2297-2299 (1987)

To a mixture of 100g (0.555 mol) of 2,5-dimethoxyacetophenone and 70.5 g (1.25 mol) of potassium hydroxide in 500 mL of triethylene glycol was added 80 mL of 85% hydrazine hydrate. The mixture was refluxed for 4 h with removal of water by distillation, allowing the pot temperature to reach 190°C, and then refluxed for another 1 h. The cooled reaction mixture and aqueous distillate (which contained some codistilled product) were combined, diluted with 1 L of water, and extracted
with CH2Cl2 (5x100 mL). The combined organic fraction was dried over MgSO4, filtered, and reduced in vacuo to give an oil, which was further purified by vacuum distillation to give 73.4 g (80% yield) of a colorless oil: bp 104-105°C/7mmHg.

L_jamf

  • Guest
rhodium, you recommend that one should ...
« Reply #4 on: September 12, 2003, 07:53:00 PM »
rhodium, you recommend that one should "never use calculated boiling points for identification purposes, as nomographs and the like seldom are very reliable," but which properties would you try to match for purposes of product identification? is index of refraction at room temperature a good identifying trait?

since swis only obtained product at 65 degrees centigrade (and not the anticipated temperature), swim suspects that the purity of the fraction is definitely questionable. swim thinks that refractionation with a shorter column might be a good idea, as 30 cm is a long for a vigreux column (too much of a temperature gradient generated). in that vein, how much substance is swis working with? based on that reference, swim suspects it can't be much more than 100 mL  ;) .

also, has swis considered using a chaser solvent? swim knows that it's a good technique when product losses in a column are considerable.

were swis to move onto another step in a synth, how would impurities affect the next portion of that synth? that would be swim's concern, as it could very well botch things to have extraneous side-reactions subtracting from the yield of the next portion of the procedure.

(-1)^(.5) think swis is on the right track and that his penchant for detailed documentation is valuable to the site, especially for a newbee like myself.

kudos (mmmm, they taste good)


Rhodium

  • Guest
Identifying products requires analytical equipment
« Reply #5 on: September 13, 2003, 03:15:00 AM »
which properties would you try to match for purposes of product identification?

You should rather use measured bp's from the literature, or if possible perform a atmospherical boiling point test.

Calculated vacuum bp's can be very different from real world data, and should only be used to give a rough idea about identity.

is index of refraction at room temperature a good identifying trait?

Yes, using a good refractometer, and performing the measurement at the same temp as the literature reference value.

The traditional way of identification has always been to measure the melting point of the substance (or of a derivative if it is a liquid). See for example

Post 443176

(Rhodium: "More articles about Ephedrine/Pseudoephedrine", Stimulants)
where they identify the products through reporting the melting points, boiling points, density, refractive index, specific rotation, solubilities, crystal shapes, elemental analysis, and even the mp for 3-7 different salts/derivatives of each isomer is presented (where applicable). It takes time and patience to identify something with 100% certainity.

TLC can usually also be used to give a good hint of identity, especially if you have a reference sample to compare with.

If all identification tests are inconclusive, but you have verified by TLC that you have a pure substance which is dissimilar to your starting material, then assume that you have gotten your desired product and continue to the next step in your synthesis. Then see if you can prove the identity of THAT substance using any of the above methods, and if you arrive at the conclusion that you at that point have the substance you should have, then you can assume that the intermediate also was the correct substance.

Proving the identity of any substance without sophisticated analytical equipment is a hard task, and you usually need to combine clues from several methods to be able to determine anything with a good degree of confidence.

scarmani

  • Guest
Saga Continues
« Reply #6 on: September 24, 2003, 04:45:00 AM »
Thank you highly, Rhodium.  Encouragement has been extracted from you.

After feeding circus peanuts to albino pachyderms, the following data were obtained.  They continued the sequence of strange undulations until the crowd was stilled into a diethyly quiet.  You could hear a pin drop, or a reaction fume.  It was like Lincoln's tomb... but don't assume.

The first packet quoted a religious text:

"A solution of 8.16 g of 2,5-dimethoxy-1-ethylbenzene in 30 mL CH2Cl2 was cooled to 0 °C with good stirring and under an inert atmosphere of He. There was then added 11.7 mL anhydrous stannic chloride, followed by 3.95 mL dichloromethyl methyl ether dropwise over the course of 0.5 h. The stirred reaction mixture was allowed to come up to room temperature, then held on the steam bath for 1 h. The reaction mixture was poured into 1 L water, extracted with 3x75 mL CH2Cl2, and the pooled extracts washed with dilute HCl. The organic phase was stripped under vacuum yielding 10.8 g of a dark viscous oil. This was distilled at 90-110 °C at 0.2 mm/Hg to yield a colorless oil that, on cooling, set to white crystals. The yield of 2,5-dimethoxy-4-ethylbenzaldehyde was 5.9 g of material that had a mp of 46-47 °C. After purification through the bisulfite complex, the mp increased to 47-48 °C. The use of the Vilsmeier aldehyde synthesis (with POCl3 and N-methylformanilide) gave results that were totally unpredictable. The malononitrile derivative (from 0.3 g of this aldehyde and 0.3 g malononitrile in 5 mL EtOH and a drop of triethylamine) formed red crystals which, on recrystallization from toluene, had a mp of 123-124 °C"

The remainder of the information appeared to be an attempt at reproduction, but at an enlargement of twofold.

"The following procedure was performed under a fume hood.

16.4 grams of 2,5-dimethoxy-1-ethylbenzene (pale yellow oil; crude product from the Clemmensen reduction of 2,5-dimethoxy-acetophenone; fractionated under vacuum: the fraction with a b.p. of 65 C @ 0.7 mm Hg) was placed in a 250 mL roundbottomed flask that had been resting in an icebath.  65 mL of dichloromethane was added, followed by a stirbar.

a two way adapter was placed in the neck of the flask and clipped.  a thermometer/inlet adapter, with hose barb, was placed in the vertical arm and clipped.   a thermometer was inserted through inlet adapter and clamped.

a vacuum adapter (for the introduction of inert gas through hose barb) was placed in the side arm of the two way adapter and clipped.  a syringe adapter (an inlet adaptor fitter with a rubber self-sealing plug through which air-sensitive reagents could be injected), was placed in the neck of the vacuum adapter and clipped.

rubber tubing was attached to both hose barbs, and the flow of inert gas through the glassware was started by weighting down the rubber nozzle of a large Helium tank.

once it seemed that flask had been flushed of atmosphere, and the temperature of the flask's contents was 0 C, a 100 mL vial of stannic chloride (SnCl4) was retrieved.  magnetic stirring was started.  a square of Parafilm was prepared in advance of vial-uncapping, because it was expected that SnCl4 would fume heavily in air.

the cap of the vial was removed cautiously, and moderately vigorous white fuming was rapidly cut off by placement of parafilm over neck of vial.

a gas-tight syringe was used to pierce the Parafilm membrane and draw several milliliters of SnCl4 for injection into the roundbottomed flask.  during the injection, magnetic stirring and the flow of inert gas through the apparatus was maintained.

the syringe was difficult to draw and had limited capacity, and it was also found that the self-sealing rubber plug of the syringe adapter was difficult to pierce, making the injection process challenging.

as the addition of the sensitive reagent progressed, the flow of Helium from the Helium tank became more rapid, probably due to the improvised method of regulating gas flow.  because it was inconvenient to interrupt the injection of the SnCl4 to adjust the flow rate of Helium, the rapid flow was allowed to continue.

As SnCl4 was added, the initially very pale clear yellow solution darkened to an amber color.  it was also noted that copious white fumes appeared at the exhaust hose as each increment of SnCl4 was added, and little transparent crystals formed at the tip. 

these fumes, venting rapidly due to the heavy flow of Helium, were not expected and caused some initial concern.  however it was concluded that they were due to SnCl4 vapor being carried along with the Helium stream and creating white fumes uppon hitting air.   it was noted that the interior of the flask remained entirely clear and free of the fumes.

with several refillings of the syringe, a total of 22 mL of SnCl4 was added.  the syringe barrel and plunger were then rinsed with DCM followed by acetone.

a 25 mL vial of Dichloromethyl Methyl Ether was then placed in the fume hood and, as with the prior injection, a square of parafilm was prepared to cover the vial after uncapping (bearing in mind the very toxic and carcinogenic nature of DCMME vapor).  the cap was removed, but when parafilm was placed over the mouth of the vial, it melted wherever it contacted the rim of the vial due to DCMME dissolution.  the parafilm was removed, the syringe was inserted through the open neck of the vial and 8 mL of DCMME was drawn without much difficulty.  The vial was recapped and returned to storage cabinet.

The syringe of DCMME was injected through the syringe adapter and supported in place by resting on a clamp.  Over the course of 30 minutes, the 8 mL of DCMME was manually added dropwise through the syringe into the mixture.  Maintaining a steady drip rate over the 30 minute period through the syringe was a labor-intensive operation.

as the first few drops hit the DCM/precursor/SnCl4 mixture, it turned dark brown.  over the course of the 30 min addition, the dark color deepened and developed into an intensely dark metallic green.  the temperature remained steady at 0 C.

midway through the addition of DCMME, the flow of inert atmosphere was checked and found to be nonexistant.  The Helium tank was checked and found to be empty.  this caused profound concern because it was initially considered that reaction could not continue unless inert atmosphere flow was maintained.  However, after second thought it was noted that the flask was still filled with inert atmosphere, and no fumes were observed either inside the flask or coming from the exhaust hose.  It was reasoned that if air diffused into the reaction flask, the worst outcome was some degree of fuming (which had already occurred), and a quantitatively minor destruction of SnCl4 reagent.

therefore, the addition of DCMME was continued and a hose clamp was placed partially tightened on the exhaust hose to retard diffusion of air into reaction vessel.

Once the DCMME addition was completed, the icebath was removed and the reaction vessel (still deep green) was allowed to come up from 0 C to room temperature over the course of about 30 minutes with continued stirring.  no visible changes occurred.

while the reaction flask was coming to room temperature, a large beaker of water was brought to a boil, to serve as a steam bath.

upon reaching room temperature, the flask was placed over the beaker of steaming water and brought to a heat of about 50 C.  at this point, it was noticed that boiling in the flask had begun, and small puffs of white SnCl4 fumes were being emitted by the exhaust hose.  the solution had turned an darkly obsidian, iridescent, metallic green-blue.

because of the toxicity of DCMME, and desire to avoid boiling and fumes since no reflux was mentioned, aluminum foil around the mouth of the steam-water flask was removed, reducing amount of steam retention and lowering heat of reaction flask.  the fumes at the exhaust hose subsided and boiling slowed to a mild rate.

temperature was maintained, with continued stirring, at ~45 C for duration of 1 hour. 
by the end of this period, the 2 foot length of rubber exhaust tubing turned dark green and appeared degraded by corrosive fumes.  the solution had turned quite dark, almost black.

after the reaction apparatus had been disassembled, it was also noted that the self-sealing rubber injection plug for the syringe adapter had been attacked by the aggressive reagents used.  the tips and edges of the rubber appeared charred and the interior hollow had turned from rubber-red to black.


at the end of the hour, the "steam-bath" was removed and stirring discontinued.  The apparatus was dismantled and the reaction was cautiously quenched by pouring mixture into 2 L cold water under the fume hood.

Small amounts of thick, heavy gray fumes were generated and clung to the surface of the water.  Huge globules of the DCM-based reaction mixture gathered at the water's surface and plumetted through the water, forming a very dense dark layer of liquid at the bottom of the container.

After being allowed to rest for 1 day, mixture was retrieved from storage cabinet.  Most of the water was poured off, and the remaining water and bottom layer of DCM/reaction mixture were extracted three times with 150 mL of DCM.  Again, this was an interesting process to observe, as the water and DCM layers remained clearly distinct, with the DCM efficiently retrieving all the oily product residue that clung to the  sides of the flask, and then cascading through the water in dense, darkly colored globules and droplets and merging with the dense organic layer.

The ~500 mL of pooled DCM extracts were then washed once with dilute hydrochloric acid, prepared by adding 4 mL of 37% hydrochloric acid to 200 mL of water.  The DCM extracts remained a dark brown-black color during the washing, and the dilute hydrochloric acid remained clear.

The DCM layer was separated and set aside for future fractionation.



Questions:

Although no fuming was observed in reaction flask, what is the likelihood that lack of inert gas flow during much of the reaction resulted in undesired results?

Was the fuming observed during the addition of the SnCl4 to be expected, or did it signal inadequate inert atmosphere procedures?  Is the vapor pressure of SnCl4 at 0 C sufficient to explain the observed fumes?

When reaction was placed over steam bath, was it problematic that reaction mixture begain to boil at 50 C?  Was it better to maintain reaction at reflux? or to reduce heat.  Was 45 C an adequate temperature for the procedure as described?

In regards to the attack of the reagents on the rubber venting hose, and more significantly the rubber syringe inlet, what modifications are advisable to avoid excessive corrosion?  Is the use of disposable septa recommended with aggressive reagents?

Is it expected that the washing of the DCM extracts with the dilute hydrochloric acid did not visibly remove any component of the reaction mixture?

Given the description, would it be advisable to proceed with the fractionation of the reaction mixture under vacuum, with the aim of isolating the desired product, 4-ethyl-2,5-dimethoxybenzaldehyde?

Along the lines of fractionation technique, is it useful to swathe the Vigreux column in cotton in order to speed the climb of vapor up the column?"

thus concluded the latest Werd of this twisted tale.  additional elephants may be bamboozled in the near future.  Werd.


scarmani

  • Guest
Changing Title of Thread?
« Reply #7 on: September 27, 2003, 05:56:00 AM »
Swim would like to change the title of this thread, but swim notices that the "Edit" option has dissapeared.  Swim would like to avoid crossposting or making redundant posts, but the initial name of the thread no longer describes its current contents. 

Could a moderator rename the thread?  Or should swim begin a new thread?  Swim says thanks.