Solvents Boiling Above 100°C Which Have an Azeotrope with Water Boiling Less than 100°C

Solvent	Boiling Point  (bp)	Azeotrope (bp)	% Water
Nitromethane	101.2	83.6	24
Pentachloroethane	162	95.9	--
1,1,2-Trichloroethane	113.8	86	16.4
Nitroethane	114	87	28
Dimethylsulfate	189	98.6	73
Epichlorohydrin	115	88	25
Methylchloroacetate	131	93	36
1-Chloro-2-propanol	127	95	46
1-Nitropropane	131	92	36
2-Nitropropane	120	89	29
Propylnitrate	110	85	25
Pyrazine	114	96	40
2-Ethoxyethanol	135	99.4	70
1-Methoxy-2-propanol	118	96	49
2-Methoxy-1-Propanol	130	98	67
Pyridine	115	94	41
Cyclopentanone	130	95	42
Cyclopentanol	141	96	58

A convenient property of solvents is that they have low boiling points. There are common solvents with boiling points above 100°C but their frequent use is usually because of some special properties and rather in spite of their high boiling points. In the table above I list less common solvents that are relatively high boilers but have the advantage that they possess an azeotrope with water that can distill at less than 100°C. Perhaps if this is more widely known they will get more usage.

Of these, pentachloroethane is toxic and does not seem to have any compensating virtue.

1,1,2-trichloroethane may be useful as an extraction solvent because it is more likely to be the more dense, lower layer in a liquid-liquid extraction. The lower phase is more convenient to remove from the reactor. Even as a cosolvent for extracting lipophilic materials it is likelier to give a lower layer.

Dimethylsulfate was used as a chemical weapon in WW1. It is a potent methylating agent. The first methyl is transferred to nucleophiles much more easily than the second. Although Wikipedia says that it reacts with water, this rate of reaction is not particularly consequential if it occurs at all. It can be steam-distilled and forms an azeotrope with water as you can see in the table. It can be used in excess for methylations since the excess can be removed as an azeotrope with water.

Both pyridine and pyrazine are miscible with both water and organic solvents yet they can be extracted into water as salts with such acids as oxalic, citric, or tartaric. 

pKas of Common Organic Substances.

What does pKa mean? The pKa of a neutral molecule or ion is the negative logarithm of the dissociation constant of a particular hydrogen atom under defined solvent conditions.  Thus for a molecule A with a particular attached hydrogen H that we designate as A-H then Ka=[H⁺] [A^- ] / [H-A] this is the hydrogen ion concentration in the solution multiplied by the concentration of the anion of A all divided by the concentration of the undeprotonated H-A.  pKa is –log Ka = -log [H⁺] –log [A^- ] + log [H-A].  

pKa = pH –log [A^- ] + log [H-A]  

pKa is best understood as the pH at which equal amounts of H-A and A^- exist in the solution. Put another way the pK is the pH at which H-A is one-half deprotonated in the reference solution.

The concept is not just applied to neutral substances or substances that are commonly recognized as Bronsted acids.  Basic molecules are also characterized by pKa values but these are the pKas of the corresponding fully protonated base.

then Ka=[H⁺] [B] / [H-B^+; ] pKa is –log Ka = -log [H⁺] –log [B] + log [H-B⁺] 

Thus pKa= pH –log [B] + log [H-B⁺]   

The solvent systems commonly used are aqueous sulphuric acid for measuring the pKa of strong acids.  The pKas of strong acids are usually negative numbers.  The more negative the number, the stronger the acid.  The strongest commonly known acid is hydrogen iodide.

Water is the solvent used for measuring the pKa of moderate acids and DMSO is common for measuring the pKas of weak acids such as the important class of carbon acids (hydrogens bonded directly to a carbon). 

As an example of the proper interpretation of the pKa acidity of a particular proton, we can note the two pKas important for the common solvent methanol, The pKa of Me-OH₂ is -2.5 and the pKa of the hydrogen bonded to oxygen in neutral methanol, Me-OH, is 15.5.  What the first number says is that at a pH of -2.5 (something like molar sulphuric acid), methanol in the solution is one-half protonated.  The second number tells me that even in the strongest aqueous base (pH 14) methanol is not yet half deprotonated.

Traditional Bronsted Acids	pKa
HI	-10
HBr	-9
HCl	-8
CF3SO3H	-5.1 (-5.9)
HClO4	-5.0
FSO3H	-4.8 (-6.4)
PhSO3H	-2.8
H2SO4	-2.8
HNO3	-1.3
CF3CO2H	-0.6
CCl3CO2H	-0.5
H3PO4	2.1
HF	3.2
H2CO3	3.7

In the same vein, one can look at the pKas of common protic solvents.

Acids with Deprotonated Form as Common Bases	Approx pKa
Isopropanol (isopropoxide)	17.1
t-butanol  (t-butoxide)	18.0
cyclopentadiene (cyclopentandienyl anion)	18.1
acetylene (acetylide)	25.0
triphenylmethane (triphenylmethide)	30.6
diisopropylamine (diisopropylamide)	39.0
ammonia (amide)	41.0
benzene (phenyl lithium)	43.0
ethane (like butyl lithium)	50.0
methane (methyl lithium)	58 ± 5

The table below shows the pKas of different common carboxylic acids.

Acidity of Carboxylic Acids	pKa	Reference Solvent
CF3CO2H	-0.6	water
CCl3CO2H	-0.5	water
HO2CCO2H	1.25	water
Cl2HCO2H	1.35	water
FCH2CO2H	2.60	water
ClCH2CO2H	2.86	water
O2N-Ph-CO2H	3.44	water
HCO2H	3.75	water
HO-CO-OH	3.70	water
PhCO2H	4.20	water
PhCO2H	11.0	DMSO
CH3CO2H	4.76	water
CH3CO2H	12.3	DMSO
H2N-Ph-CO2H	4.92	water
H2N-CO2H	9.8	water

The pkas of the conjugate acids of solvents are a guide to how active a Bronsted acid will be in different solvents, The more negative the pKa the more reactive the proton will be.

Conjugate Acids of Possible Solvents	pKa
CH3SCH3	-6.99
CH3O-Ph	-6.5
Ph-COOEt	-6.2
CH3OCH3	-3.8
(CH3)2CO	-2.85
CH3OH	-2.5
H2O	-1.7
CH3SOCH3	-1.5
NH2(CS)NH2	-1.26
H ( CO )NH2	-0.48
CH3(CO)NH2	0.1
NH2(CO)NH2	0.5
NH2CH2CO2H	2.35

Probably the most valuable table is the one showing carbon acids alongside other reference acids. This helps when deciding how strong a base is required for a particular deprotonation.

Organic acids	pKa
PhSO2H	1.2
PhCH=NHOH (a protonated oxime)	2.0
MeSO2H	2.3
HNO2	3.4
MeCOSH	3.4
H2CO3	3.7
P{hCH2NH2OH (a protonated hydroxylamine)	4.9
PhNHMe2 (protonated dimethylaniline)	5.1
PyrH (protonated pyridine)	5.2
MeNH2OH (protonated N-methyl hydroxylamine)	6.0
Thiophenol	6.5
H2S	7.0
phthalimide	8.3
PhB(OH)2	9.0
acetylacetone	9.0
ammonium ion	9.2
succinimide	9.6
NH4CO2 (carbamic acid zwitterions)	9.8
Phenol	10.0
Nitromethane	10.0
bicarbonate	10.2
Thiophenol (in DMSO)	10.3
Ethanethiol	10.6
Cyclohexyl ammonium	10.7
triethyl ammonium	10.8
2-carboxyethyl cyclohexanone (beta keto ester)	10.9
acetone enol	11.0
Diethylammonium	11.0
Dicyanomethane	11.4
Hydrogen peroxide	11.6
2-indanone	12.2
PhCH2NO2	12.3
CF3CH2OH	12.4
Methyl cycanoacetate	12.8
guanadinium ion	13.4
ethylacetoacetate (DMSO)	14.2
imidazole	14.5
methanol	15.5
water	15.7
ethanol	15.9
Phenylacetone	15.9
acetaldehyde	16.5
2-nitropropane	16.9
isopropanol	17.1
t-butanol	18.0
cyclopendadiene	18.1
thioacetamide	18.5
acetone	19.2
nenzylcyanide	21.9
diphenylamine	23.5
chloroform	24
phenyl methylketone	24.7
acetylene	25
acetamide	25.5
urea	26.9
3-pentanone (DMSO)	27.1
Phenyl methyl sulfone (DMSO)	29.0
ethyl acetate	30.5
triphenylmethane	30.6
2-phenyl-1,3-dithiane (DMSO)	30.7
Dimethylsulfone (DMSO)	31.1
acetonitrile (DMSO)	31.2
diphenylmethane (DMSO)	32.3
N,N-diethylacetamide (DMSO)	34.5
diisopropylamine (THF)	35.7-39
ammonia	41
toluene (DMSO)	43
benzene (CHA)	43
ethylene	44
propylene	47.1-48.0
ethane	about 50