David B. Collum
Associate Editor
The Journal of Organic Chemistry
Phone: 607- 255-5023
eFax: 202-513-8662
Email: joch2@cornell.edu
September 6, 2010
Dear Prof. Collum,
I am hereby submitting the revised version of the manuscript jo-2010-01409p for
your consideration. Yours and referees’ suggestions have been taken into account
to make the article corresponding to the requirements as detailed below.
Sincerely yours,
Professor Ivo Leito
University of Tartu
Institute of Chemistry
Ravila 14a, 50411 Tartu
ESTONIA
phone: +372-5-184-176
fax: +372-7-375-264
e-mail: ivo.leito@ut.ee
1
RE: The Journal of Organic Chemistry
Manuscript ID: jo-2010-01409p
Title: "Equilibrium Acidities of Superacids"
Author(s): Kütt, Agnes; Rodima, Toomas; Saame, Jaan; Raamat, Elin; Mäemets,
Vahur; Kaljurand, Ivari; Koppel, Ilmar; Garlyauskayte, Romute; Yagupolskii,
Yurii; Yagupolskii, Lev; Bernhardt, Eduard; Willner, Helge; Leito, Ivo
Thank you for submitting your manuscript for publication in The Journal of
Organic Chemistry (JOC). Your manuscript has been examined with the assistance
of expert reviewers who have evaluated its scientific merit and potential for
interest to the readership of the JOC. I have also reviewed your manuscript in
my office in light of their comments which are attached. On balance this
assessment is positive although some revisions are recommended. I am pleased to
invite you to submit a revised manuscript that addresses the concerns raised by
the reviewers.
To submit your revised manuscript, log into ACS Paragon Plus at
http://paragonplus.acs.org/login and select "My Authoring Activity". There you
will find your manuscript title listed under "Revisions Requested by Editorial
Office." All of your original files (except your original manuscript) are
available to you when you upload your revision. If you are replacing files,
please remove the old version of the file before uploading the new file.
When submitting your revised manuscript through ACS Paragon Plus, you must
respond to the comments made by the reviewer(s). Please use the text box
provided in the "Response to Decision Letter" section of the revision submission
Web form to indicate your detailed responses to all of the points raised by the
reviewers. You also have the option of providing an attached file with the
detailed responses.
Per our Guidelines for Authors, "if the revised manuscript is not returned to
the Editor within 45 days after the revision is requested, and the author has
not made alternative arrangements with the Editor for completion of the
manuscript, the manuscript will be deactivated".
We hope to see your revised
manuscript before October 5.
Prior to submitting the manuscript, please ensure that the manuscript satisfies
the following requirements:
Round off 13 C NMR.
Answer: 13C NMR shifts in spectra have been round off.
Number SI pages sequentially.
Answer: all SI pages have been now numbered.
Thank you for considering The Journal of Organic Chemistry as a forum for the
publication of your work.
With sincere regards,
David B. Collum
Associate Editor
The Journal of Organic Chemistry
Phone: 607- 255-5023
2
eFax: 202-513-8662
Email: joch2@cornell.edu
-----------------------------------Reviewer(s)' Comments to Author:
Reviewer: 1
Recommendation: Publish in The Journal of Organic Chemistry after minor
revisions.
Comments:
A comprehensive study of 62 acids and superacids in DCE is presented employing
176 interlinked relative acidity measurements, thus providing the largest and
most accurate superacidity scale to date. I concur with assessment that DCE is
the most convenient solvent for acids. My only objection is that in discussing
delocalisation in cyanoacid anions some papers of Vianello et al. were not
mentioned. These computational studies have convincingly shown that the excess
negative charge was very efficiently dispersed over conjugate bases making them
weakly coordinating negative ions.
Answer: The referee 1 is correct. Vianello et al. have published several
computational papers concerning cyanocarbon acids and one of them has now been
included to the list of references as ref. 29.
I strongly recommend publication of this valuable paper.
Additional Questions:
Significance: Top 10%
Interest to The Journal of Organic Chemistry readership: Top 10%
Scholarly analysis/presentation: Above Average
Are the conclusions adequately supported by the data?: Yes
Are the literature references appropriate and correct?: No
Are the compounds reported adequately characterized with regard to identity and
purity?: Yes
Reviewer: 2
Recommendation: The manuscript may be publishable, but it should be reviewed
after major revisions.
Comments:
This paper reports a valuable and potentially useful compilation of relative
acidity data. It represents a lot of painstaking work. The choice of 1,2dicholorethane as solvent is a good one and the relatively broad array of
investigated acids (with the notable absence of alkoxyaluminate, pentacyanocyclo-pentadienyl and carborane acids) makes the work relevant to practicing
chemists.
However, the presentation is flawed.
3
Answer: Some of the seemingly flawed points Referee 2 brings up could be
explained and corrected as follows.
(a). The title, abstract, table headings etc. imply that relative pKa values are
being measured when, in fact, it is the relative equilibrium tendencies of acids
to form a protonated phosphazene ion pair, presumably one that is H-bonded to
its anionic conjugate base.
Answer: This is a very important question. There is very strong evidence against
hydrogen-bonding between acid anion and protonated phosphazene base. For the
sake of completeness we present it here and also in the SI of the paper so that
it will be available for the readers.
(1) Low hydrogen bond donicity of the protonated phosphazenes was among the
goals for which phosphazene bases were initially developed by the Schwesinger
group (Liebigs Ann. 1996, 1055-1081). The proton in the protonated forms of the
bulky phosphazene bases is buried between substituents. This is especially true
if the substituent on the imino nitrogen is bulky (t-Bu in our case) and if the
substituents on the phosphorus are large, such as pyrrolidinyl (our case), tmg,
etc. The hindrance of the proton in protonated phosphazenes has been
demonstrated by X-ray diffractograms (Liebigs Ann. 1996, 1055-1081; JACS 2005,
127, 17656-17666). A particularly noteworthy feature of phosphazenium cations in
the context of this paper is their ready applicability in preparation of the socalled "naked fluorides" (Angew. Chem. Int. Ed. Engl. 1991, 30, 1372-1375).
Cations behaving as inert towards the highly HB-acceptory fluoride anion can be
safely considered the same with respect to all anions of this study.
(2) The absence of hydrogen bond between the protonated phosphazene base and
acid anions is also seen from the UV-Vis spectra that are recorded during the
measurement. When phosphazene base t-BuP1(pyrr) is used as titrant no distortion
of the spectra of acid-anion mixtures are observed. At the same time, titration
of some of the acids (1, 13, 17, 21, 24, 28, 29) with triethylamine (or being
originally triethylammonium or pyridinium salts) caused distortion of the
spectral plot (a hypsochromic shift of the maximum of spectrum) and strongly
non-consistent results. This is a clear indication of formation of a hydrogenbonded complex. The same effect was never experienced with t-BuP1(pyrr). For
double-checking some of the compounds were also titrated with an even bulkier
base t-BuP4(dma) and the spectra matched with the spectra obtained from the
titration with base t-BuP1(pyrr). The t-BuP1(pyrr) base was preferred because it
is commercially available with reasonable purity and price.
Thus, we might have relatively loosely bound ion pairs between sterically
hindered huge cation (with diameter over 9Å) and different anions of (mostly)
CH acids with well delocalized negative charge (which is also said in the text),
but not hydrogen-bonded complexes.
The latter point carries a particular irony. The authors correctly critique the
so-called NH acidity scale as an indirect method that characterizes the
hydrogen-bond acceptor strength of anions rather than the Brønsted acidity of
their parent acids.
Answer: Because trioctylammonium salt form hydrogen-bonded complexes to the acid
anion, then NH scale does not characterize the acidity of free acid but the
ability of acid anion to form hydrogen-bonded complexes with protonated
4
trioctylamine (which of course is also very useful). Therefore, in a general
case, it does not show Brønsted acidity, which assumes complete transfer of the
proton to the anion.
But they fail to see in their own work that their relative ion-pairing
equilibria are also dependent on the relative hydrogen-bond acceptor strength of
their anions.
Answer: As explained above (vide supra), there is very strong evidence against
this.
Indeed, it would be an interesting study to see IR nuNH data on the ion paired
phophazenium salts to see how (or if) their NH IR frequencies correlate (or not
correlate) with the relative ion pairing equilibria data.
Answer: As we do not have hydrogen-bonded complexes between acid anion and
protonated phosphazene base (as explained above) then NH IR frequencies should
depend only on the nature of the base and probably on the properties of ion pair,
not on the nature of acid anion. An obstacle for such IR study is the very low
concentration of the acids in our experiments and the low transparency of 1,2DCE in the mid-IR region.
Table 1 should also asterisk the value of picric acid as arbitrarily set to 0.
Answer: pKa value of picric acid has now been marked as arbitrarily chosen
anchor point 0 in the footnote of Table 1.
(b) The experimental section does not detail the method or the nature of some of
the acids. The reader is referred to earlier papers. Ref. 24 states that a
typical acid concentration was 5 x 10(-5)M. If this is the case in the present
work, then many of the data may be highly suspect. It is experimentally very
difficult to keep the concentration of water in any solvent below 10(-4)M. Thus,
some of the acids will be H30+ or more highly hydrated salts.
Answer: The "backbone" of the scale was built with CH acids, which are not
influenced by water to a large extent (see ref 22 of the main text for details).
This is because their anions have highly delocalized charge. A detailed study on
influence of traces of water in acetonitrile has been carried out in our group
and is in the process of publication (JPCA, MS No jp-2010-05670t). The results
show that even the relative acidities of acids having delocalized charges in
their anions are not much influenced up to ca 10000 ppm. Certainly the situation
in 1,2-DCE is less favorable. However, the water content was also more than
three orders of magnitude lower.
A particular concern is so-called HBF4. It does not exist. Out of a bottle it
is either solvated by HF, i.e. H(HF)n+ BF4- (if it is truly anhydrous) or H3O+
BF4-, H5O2+ BF4-, etc depending on the amount of water present.
Answer: Indeed, this is a tricky acid, not supposed to exist as such.
Nevertheless titration of Bu4N+ BF4– with acid 64 and afterwards with base tBuP1(pyrr) demonstrated the reversibility of the protonation-deprotonation
process. The formed complex HF∙∙∙BF3 seems to be stable in solution because of
5
its very low concentration and the extremely low Lewis basicity of DCE. The acid
also behaves very consistently: three measurements were carried out with it (see
Table 1) and their results are consistent with the measurements not involving
HBF4. During this experiment, it is impossible, that the acidity of pure HF was
measured by mistake (based on the moles of titrants consumed). HF is also such a
weak acid (considerably weaker than HCl) that it could not be included into the
present scale. We cannot, however rule out that the acidic species involved was
actually a hydrate, such as H2O•HBF4. This explanation along with a word of
caution has been added to the text.
The skeptical reader will wonder about the role of water in this work which does
not seem to have been explored systematically. Reproducibility of data does not
mean they are correct. It may simply mean that the water content is reproducible.
Some data may refer to ion pairs; other may refer to water-bridged ion pairs.
Answer: See above the comments on the influence of water. Table 1 includes 62
acids of different chemical nature (CH, NH, OH, etc.) which are interconnected
by 176 separate measurements of the direct acidity differences (pKa values)
between these acids. The overall acidity (i.e. free energy) change between acids
#1 and #62 is 15.3 pKa units and according to the fundamentals of the
thermodynamics (Hess Law) this overall acidity change results when separate pKa
values between arbitrarily chosen collection of acids are summed up. Indeed, one
can see that the additive stair-stepping overlapping (Table 1) really holds and
it is not dependent on the selection of the acids involved. Since the water
content during measurements was not very reproducible – varying by a factor of 5,
this consistency would not have been achieved if water would be directly
involved in the process.
There is no spectroscopic data presented to inform on this. It is possible that
the data on large organic acids are not very susceptible to traces of water but
the data on smaller, inorganic acids are much more likely to be so. Without
systematic studies on measured water concentrations all the data must be
taken ?con granulo salis?.
Answer: Please see the answers above.
In summary, the authors are to be commended for taking on a very difficult task.
The paper could be a very important contribution but it overreaches (a) and is
potentially seriously flawed (b).
Additional Questions:
Significance: Above Average
Interest to The Journal of Organic Chemistry readership: Above Average
Scholarly analysis/presentation: Above Average
Are the conclusions adequately supported by the data?: No
Are the literature references appropriate and correct?: Yes
Are the compounds reported adequately characterized with regard to identity and
purity?: No
6