DOI:10.1021/jo101589h
Published on Web 10/14/2010J.Org.Chem.2010,75,8351–83548351
r 2010American Chemical Society
/joc
Drying of Organic Solvents:Quantitative Evaluation of the
Efficiency of Several Desiccants
D.Bradley G.Williams*and Michelle Lawton
Rearch Centre for Synthesis and Catalysis,Department of Chemistry,University of Johannesburg,
P.O.Box 524,Auckland Park 2006,South Africa
bwilliams@uj.ac.za Received August 12,
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2010
Various commonly ud organic solvents were dried with veral different drying agents.A glovebox-bound coulometric Karl Fischer apparatus with a two-compartment measuring cell was ud to determine the efficiency of the drying process.Recommendations are made relating to optimum drying agents/conditions that can be ud to rapidly and reliably generate solvents with low residual water content by means of commonly available materials found in most synthesis laboratories.The practical method provides for safer handling and drying of solvents than methods calling for the u
of reactive metals,metal hydrides,or solvent distillation.
Introduction
Laboratories involved with synthesis require efficient methods with which to dry organic solvents.Typically,prescribed methods 1are taken from the literature where little or no quantitative analysis accompanies the recommended drying method.Frequently,such methods call for the u of highly reactive metals (such as sodium)or metal hydrides,which increas the risk of fires or explosions in the laboratory.This situation is aggravated by hot solvents that are prent during the distillation process that removes the solvent from the desiccant.While many laboratories employ relatively expensive commercially available drying trains that u filled cartridges to dry solvents (the systems appear to be largely bad on the pioneering work of Grubbs 2in this context),a large number of laboratories do not have access to such
facilities.Accordingly,urs of the published drying methods rely upon procedures that generally have little or no quanti-fied basis of application and generate samples of unknown water content.In a rather elegant exception,Burfield and co-workers published a ries of papers 3some three decades ago in which the efficacy of veral drying agents was investi-gated making u of tritiated water-do
ped solvents.The drying process was followed by scintillation readings,and veral shortcomings were noted in “standard”drying prac-tices.Despite this rather extensive analysis,many of the methods identified as inept are still in u today.
In altogether a different context,we required solvents that were reliably dried to levels of water in the sub-10ppm range in order to test some principles of Lewis acid catalysis.4Since even the notable work of Burfield did not give the information needed to prepare super dry solvents required for our earlier study,we investigated the drying of veral solvents as followed by coulometric Karl Fischer titrations.The titrator instru-ment was houd inside a glovebox for ultimate analytical nsitivity andinstrument stability.While veral other methods 3,5
(1)(a)Perrin,D.D.;Armarego,W.L.F.Purification of Laboratory Chemicals ;Pergamon Press:New York,1988and references cited therein.(b)Furniss,B.S.;Hannaford,A.J.;Smith,P.W.G.;Tatchell,A.R.Vogel’s Textbook of Practical Organic Chemistry ,5th ed.;Pearson:Harlow,1989and references cited therein.
(2)Pangborn,A.B.;Giardello,M.A.;Grubbs,R.H.;Ron,R.K.;Timmers,F.J.Organometallics 1996,15,1518.
(3)(a)Burfield,D.R.Anal.Chem.1976,48,2285.(b)Burfield,D.R.;Lee,K.H.;Smithers,R.H.J.Org.Chem.1977,42,3060.(c)Burfield,D.R.;Gan,G.H.;Smithers,R.H.J.Appl.Chem.Biotechnol.1978,28,23.(d)Burfield,D.R.;Smithers,R.H.J.Org.Chem.1978,43,3966.(e)Burfield,D.R.;Smithers,R.H.;Tan,A.S.C.J.Org.Chem.1981,46,629.(f)Burfield,D.R.;Smithers,R.H.J.Org.Chem.1983,48,2420.(g)Burfield,D.R.J.Org.Chem.1984,49,3852and references cited therein.
(4)Williams,D.B.G.;Lawton,M.J.Mol.Catal.A 2010,317,68.
(5)(a)Bower,J.H.J.Res.Nat.Stand.1934,12,241.(b)Trusll,F.;Diehl,H.Anal.Chem.1963,35,674.(c)Meeker,R.L.;Critchfield,F.;Bishop,E.F.Anal.Chem.1962,34,1510.(d)Garrigues,S.;Gallignani,M.;de la Guardia,M.Anal.Chim.Acta 1993,281,259.(e)Pinheiro,C.;Lima,J.C.;Parola,A.J.Sens.Act.B:Chem.2006,114,978.(f)Veillet,S.;Tomao,V.;Visinoni,F.;Chemat,F.Anal.Chim.Acta 2009,632,203.
JOC Article Williams and Lawton have been developed for water determination in solvents,
advances to the design and nsitivity of particularly coulo-
metric Karl Fischer titrators since Burfield’s day now allow
accurate measurements of water in organic solvents at the
ppm level.6The objective of the prent study was not to
comprehensively cover a wide cross ction of drying agents
(Burfield and co-workers have already adequately per-
formed this task,highlighting problem areas in the process,
particularly in their minal paper on the topic3b)but to
generate sufficient data to allow a practical,safe,and easy-
to-reproduce approach to drying veral common solvents to
be recommended for everyday u.
Results and Discussion
廉洁文化墙
For this study,tetrahydrofuran(THF),toluene,dichloro-
methane(DCM),acetonitrile,methanol,and ethanol were
employed.Initially,the water content of the“wet”solvents
(i.e.,as obtained from commercial sources as analytical
reagent-grade or HPLC-grade solvents)was measured.Ac-
cordingly,samples of about3.0mL(the exact amount added
was accurately determined by weighing the filled syringe on a
three decimal balance inside the glovebox and also the empty
syringe after injecting the sample into the cell and calculating
the difference)were injected into the anode compartment of
the measuring cell of the Karl Fischer apparatus(n=6per
sample).Where moisture content was very low for acetoni-
trile(e below,Table4),larger sample sizes(of10.0mL)
were employed as a countercheck to ensure accuracy.How-
ever,this approach results in very inefficient u of the
Hydranal solution ud for the Karl Fischer titration and
also of rapid filling of the anode compartment of the measur-
ing cell.It was therefore not followed as a matter of cour
since the accuracy was found to be the same for the different
sample sizes.Samples of solvents removed directly from the
bottles as received were analyzed:the data are ud as a
measure against which to judge the success of a given drying
初中语文课文目录
agent for a lected solvent.When the solvents were dried,
drying was performed in triplicate.Each dried sample was
analyzed six times to provide statistically acceptable precision
data.
Tetrahydrofuran
THF is one of the mainstay solvents in synthesis labora-tories.It is often predried over KOH pellets after which it is dried by heating under reflux over sodium wire in the prence of benzophenone as indicator.1Under the condi-tions,THF was found to be dried to approximately43ppm water content(Table1).Matters significantly improve by simply allowing the solvent to stand over activated3A molec-ular sieves(Table1).Here,a20%mass/volume(m/v) loading of the desiccant allows low ppm levels to be achieved after48h.Lower mass loadings also give good results but take significantly longer(about5days)to achieve single digit ppm levels of residual moisture.Several types of silica were assd for their desiccating ability,including standard silica(70-230mesh)typically employed in gravity column chromatography.Silica of some description is readily available in most sy
nthesis laboratories making it an obvious target as a desiccant.There was esntially no correlation between pore size and drying efficiency with the various silicas ud.
A much stronger linear correlation was noted in respect of particle size,with finer particles given superior drying effi-ciencies in a given period of time(Figure1;single passage of the solvent over a column of the silica,10%m/v).While silica was reasonably good as a desiccant,neutral alumina was much better,rivaling the ultimate efficiency of molecular sieves after a single pass of the THF over a column of the activated alumina.For rapid drying,neutral alumina is the drying agent of choice,followed by storage over3A molec-ular sieves if storage is necessary.Otherwi,simple storage over3A molecular sieves provides THF with very low water content within48-72h.While THF may be polymerized to some extent upon standing with strongly Lewis/Brønsted acidic materials,this was not found to be problematic in the prent instance given the short residence time of the THF on the alumina:samples of THF that had been pasd over the alumina were evaporated to dryness with no significant residue remaining.
T ABLE1.Water Content in THF after Drying a
desiccant time(h)
residual water
content(ppm) none,“wet”solvent107.8(0.7 sodium/benzophenone b4843.4(0.7 3A molecular sieves(10%m/v)2427.7(1.0 3A molecular sieves(20%m/v)2414.7(0.3 3A molecular sieves(20%m/v)48 6.1(0.2 3A molecular sieves(20%m/v)72 4.1(0.1 silica(28-200mesh)c,d c56.2(2.5 silica(35-60mesh)c,e c105.7(3.5 silica(60-100mesh)c,e c89.4(2.8 silica(70-230mesh)c,e c82.5(1.2 silica(100-200mesh)c,e c74.6(2.9 silica(200-425mesh)c,e c59.5(3.7 silica(100-200mesh)c,f c69.0(3.3 silica(200-425mesh)c,f c60.8(1.9 neutral alumina c c 5.9(0.4 a Drying was performed in triplicate;n=6for each dried solvent analyzed,providing n=18for each desiccant.b THF was distilled from the desiccant once the indicator had turned a persistent blue color.
c Solvent was pas
d over a column of th
e desiccant,10%m/v,inside the glovebox.The system was not assd for“breakthrough”o
f , to establish the capacity of the desiccant.d Silica(pore size22A).e Silica (pore size60A).f Silica(pore size100A
).
刘瑾简介
F IGURE1.Linear dependency of the drying efficiency by columns of60A silica(10%m/v)of THF with respect to silica particle size (data taken from Table1).
(6)(a)Anonymous.Fundamentals of the Coulometric Karl Fischer Titration with Selected Applications,Mettler Toledo,Switzerland,2003.(b)Dantan,N.; Frenzel,W.;K€u ppers,S.Talanta2000,52,101.
8352J.Org.Chem.Vol.75,No.24,2010
Williams and Lawton JOC Article
Toluene
Toluene can be predried using CaCl2,CaH2,or CaSO4and
is most commonly dried by heating over sodium with benzo-
phenone as indicator.1Such treatment(Na/benzophenone)
reduced the water content from225ppm to about34ppm in
our hands(Table2).Storage of the“wet”toluene over3A
molecular sieves for24h or simple passage thereof over a
column of silica readily provided“super dry”toluene with a
moisture content in the low single digit ppm range.Either of
the methods may be conveniently ud to rapidly provide dry toluene suitable for the most demanding of reactions.
Dichloromethane
Dichloromethane is relatively easy to dry.It is not particu-larly hygroscopic,and even commercially available material has a low water content.Heating DCM over CaH2appears to be the method of choice for drying this solvent,1conditions which provided samples with a moisture content of about 13ppm(Table3).In contrast,simple storage of the solvent over activated3A molecular sieves or passage thereof over a column of activated silica provided significantly drier material with very low water content in the single digit ppm range.
Acetonitrile
Acetonitrile is a polar,aprotic solvent with high solvating ability.It has a high affinity for water and can be difficult to dry.1Burfield3b found that P2O5was particularly efficient at removing water from acetonitrile,where a desiccant loading of5%(w/v)with24h of static drying leaves a residual water content of9ppm.In our hands,as was found for THF as described above,treatment of acetonitrile with3A molecu-lar sieves or neutral alumina readily gave solvent with very low residual moisture content(Table4).Again,passage over neutral alumina followed by storage over3A molecular sieves is a highly desirable method to rapidly and confidently cure access to dry acetonitrile.The reliability of the method was checked by making u of a larger sample size,namely 10.0mL of the solvent for samples dried over3A molecular sieves(10%m/v)for24h,providing esntially identical results to tho derived from the smaller(3.0mL)sample sizes.
Methanol and Ethanol
Lower alcohols are typically dried by heating over iodine-activated magnesium with a magnesium loading of0.5-5.0g/L.1Several other desiccants,including KOH,BaO,and CaO,1,3have also been recommended.KOH and Mg/I2are found to provide methanol with a water content of33and 54ppm,respectively(Table5).Molecular sieves(3A)were efficient at drying this solvent only when prent at a loading of10%m/v or higher and when the solvent was left to stand over the sieves for a
minimum period of72h.Optimum drying is obtained with storage of the methanol over20% m/v3A molecular sieves for5days,by which time the water content reduces to about10ppm.
Ethanol behaved similarly,requiring a minimum of10% m/v of activated3A molecular sieves before efficient drying is noted,optimally also after a period of5days over10%or 20%m/v of the sieves,under nitrogen(Table6).Powdered KOH proved a rather active desiccant for methanol,and ethanol and may be ud in a predrying step prior to storage
T ABLE2.Water Content in Toluene after Drying a腊日杜甫
desiccant time(h)residual water content(ppm)
none,“wet”solvent224.9(1.3 Sodium/benzophenone b4831.4(1.9 3A molecular sieves(10%m/v)240.9(0.3 silica(10%m/v)c c 2.1(0.2 a Drying was performed in triplicate;n=6for each dried solvent analyzed,providing n=18for each desiccant.b Toluene was distilled from the desiccant once the indicator had turned a persistent blue color.
c Solvent was pas
d over a column of silica(por
e size22A,28-200 mesh)inside the glovebox.The system was not assd for“break-through”o
f ,to establish the capacity of the desiccant.
T ABLE3.Water Content in DCM after Drying a
desiccant time(h)residual water content(ppm)
none,“wet”solvent22.4(1.2 CaH2b2412.9(1.3 3A molecular sieves(10%m/v)240.1(0.1 silica(10%m/v)c c 1.3(0.3 a Drying was performed in triplicate;n=6for each dried solvent analyzed,providing n=18for each desiccant.b Dichloromethane was distilled from the desiccant.c Solvent was pasd over a column of silica (pore size22A,28-200mesh)inside the glovebox.The system was not assd for“breakthrough”of ,to establish the capacity of the desiccant.T ABLE4.Water Content in Acetonitrile after Drying a
desiccant time(h)
residual water
content(ppm) none,“wet”solvent142.0(1.2
3A molecular sieves(5%m/v)24 4.0(0.7
48 1.8(0.5
72<dl b,c
3A molecular sieves(10%m/v)240.5(0.4(0.7(0.1)d
48<dl b,c
activated neutral alumina(10%m/v)e;e 5.9(0.4hit现在分词
a Drying was performed in triplicate;n=6for each dried solvent analyzed,providing n=18for each desiccant.
b For2.6and8.7g sample sizes(3.0and10.0mL).c<dl=below detection limit of the Karl Fischer instrument.d10.0mL sample sizes(instead of the customary3.0mL)of the solvent gave the results in parenthes.e Solvent was pasd over a column of alumina inside the glovebox.The system was not assd for “breakthrough”of ,to establish the capacity of the desiccant.
T ABLE5.Water Content in Methanol after Drying a
desiccant time(h)
residual water
content(ppm) none,“wet”solvent175.1(0.4 KOH powder(10%m/v)b2433.1(0.9 Mg/I2(0.5g Mg/L)b53.6(0.6 3A molecular sieves(5%m/v)2477.3(0.7
4846.8(0.6
刘字怎么写好看7234.2(0.4
12026.5(1.1 3A molecular sieves(10%m/v)2440.6(0.6
4829.4(0.8
7220.1(0.6
12018.2(0.9 3A molecular sieves(20%m/v)2428.1(0.4
4823.1(0.6
7219.2(0.6
12010.5(0.9 a Drying was performed in triplicate;n=6for each dried solvent analyzed,providing n=18for each desiccant.b Methanol was distilled from the desiccant once the magnesium had been consumed.
J.Org.Chem.Vol.75,No.24,20108353
JOC Article Williams and Lawton
over activated3A molecular sieves to provide ultimate drying efficiency.
Conclusions
This work shows that the u of activated3A molecular sieves,silica,or alumina readily and reliably provides dry solvents with residual moisture in the sub-10ppm range.The method is practical,requires no special apparatus(apart from a column within which to hou the silica or alumina and a two-necked flask for collecting the solvent under inert atmosphere using standard Schlenk techniques),and pro-vides a safe method that does not make u of highly reactive materials such as sodium or metal hydrides.The develop-ments here clearly indicate that laboratories currently mak-ing u of such methods could consider terminating such practices in favo
r of the safer methods detailed here which are,in the event,more efficient at drying solvents.[CAUTION!We did not test for the removal of peroxides from solvents such as tetrahydrofuran,so the usual precautions should be followed(such as testing for the prence of peroxides or performing a chemical quench of the reactive species1) with solvents for which the prence of peroxides may be an issue.For a discussion on the removal of peroxides, including the u of chemical and absorptive methods (with alumina and zeolites),the reader is advid to consult ref7].亲爱的罪人
Experimental Section
Analytical reagent-or HPLC-grade solvents were obtained from commercial sources and ud as is or were dried using the various methods described herein.Desiccants(3A molecular sieves,various silicas,neutral alumina)were obtained from commercial suppliers and were predried at300°C for24h immediately before u.Solvents were dried either by allowing them to stand over the desiccant under nitrogen or by passing the solvent over a column of the desiccant as specified,inside the glovebox.Each solvent was dried in triplicate.Each dried solvent was analyzed six times,providing n=18per solvent per desiccant.A coulometric Karl Fischer titrator fitted with a diaphragm cell(this tup is preferred for low-level moisture determinations)was ud inside a glovebox under nitrogen (<1ppm oxygen,<1ppm moisture).Each part of the cell (anode and cathode)was charged with the ap
propriate com-mercial solution(Hydranal)suited thereto.The titrator was primed by allowing it to equilibrate and stabilize,which removes all residual water from the measuring cell.The accuracy of the titrator was measured against a100ppm certified reference material and gave an average reading of98.3(0.6ppm water for4.0mL sample sizes(the amount of sample added was accurately determined by weighing the filled syringe and the empty syringe after injection of the sample,using a three decimal balance inside the glovebox)of the reference material,well within acceptable accuracy and precision ranges.
Acknowledgment.We thank the University of Johannesburg, Sasol,NRF,and THRIP for funding.
T ABLE6.Water Content in Ethanol after Drying a
desiccant time(h)residual water content(ppm)
none,“wet”solvent1428.3(3.8 KOH powder(10%m/v)b2426.4(0.6 3A molecular sieves(5%m/v)24262.6(2.0
48106.5(0.7
7255.1(0.9
12014.5(0.4 3A molecular sieves(10%m/v)24186.1(0.9
4869.5(0.6
7236.9(1.0
12012.3(0.9 3A molecular sieves(20%m/v)24119.8(0.7
4825.0(0.7
7220.5(0.5
1208.2(0.4
a Drying was performed in triplicate;n=6for each dried solvent analyzed,providing n=18for each desiccant.
b Ethanol was distilled from the desiccant.
(7)Wortel,Th.M.;van Bekkum,H.J.Org.Chem.1980,45,4763.
8354J.Org.Chem.Vol.75,No.24,2010
