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Design of Exceptionally Strong Organic Superbases Based on Aromatic Pnictogen-Oxides: A Computational DFT Analysis of the Oxygen Basicity in the Gas-Phase and Acetonitrile Solution Tana Tandaric, and Robert Vianello J. Phys. Chem. A, Just Accepted Manuscript • DOI: 10.1021/acs.jpca.7b11945 • Publication Date (Web): 19 Jan 2018 Downloaded from http://pubs.acs.org on January 19, 2018

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The Journal of Physical Chemistry

Design of Exceptionally Strong Organic Superbases Based on Aromatic Pnictogen-Oxides: A Computational DFT Analysis of the Oxygen Basicity in the Gas-Phase and Acetonitrile Solution

Tana Tandarić and Robert Vianello*

Computational Organic Chemistry and Biochemistry Group, Ruđer Bošković Institute, Zagreb, Croatia * Corresponding author. Email: [email protected]. Phone: +385 1 4561117.

ABSTRACT DFT B3LYP calculations convincingly showed that aromatic pnictogen-oxides offer scaffolds suitable for tailoring powerful organic superbases exhibiting exceptional oxygen basicity in both gas-phase and polar aprotic acetonitrile solution. With their protonation enthalpies and pKa values, they surpass the basicity of classical proton sponges and related nitrogen bases. The most potent system is provided with two arsenicoxide moieties on the phenanthrene framework assisted with the two phosphazeno groups in the paraposition to both basic centers. With its proton affinity PA = 300.5 kcal mol–1, the latter system breaks the gas-phase hyperbasicity threshold of 300 kcal mol–1, while its pKa = 54.8 promotes it as an unprecedented superbase in acetonitrile. The origin of such a dramatic basicity enhancement is traced to a fine interplay between (a) steric repulsions of the two negatively charged oxygens destabilizing a neutral base, (b) a favorable intramolecular [O–H·····O]– hydrogen bonding in conjugate acids, and (c) an efficient cationic resonance upon protonation supported with the electron-donating substituents. Given the growing interest in highly basic compounds together with related basic catalysts and metal complexing agents, we hope that the results presented here would open a new avenue of research in these fields and direct the attention towards utilizing aromatic pnictogen-oxides in designing improved organic materials. 1

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INTRODUCTION Organic chemists routinely face the crucial problem of selecting the appropriate base for the catalytic reaction to be performed. Although uncharged organic bases are usually weaker than their inorganic counterparts, such as alkali-metal hydroxides, oxides and alkoxides, they have become widely used standard reagents in a broad range of chemical transformations in organic syntheses and technological processes.1–5 This is because they offer several advantages over their ionic counterparts, including milder reaction conditions, efficient solubility in most organic solvents, reduced nucleophilicity, very good stability at low temperatures, excellent recycling possibilities, and absence of a coordinating metal ion.6 With their unique characteristics, strong neutral bases enable the deprotonation of a vast array of weakly acidic systems to allow weakly coordinated and highly reactive anionic species. Therefore, it comes as no surprise that during past decades a lot of research attention has been focused on the computational design and experimental preparation of neutral organic superbases and proton sponges,7,8 as well as on the evaluation of their basicity constants and catalytic efficiencies in various solvents.9–12

The concept of superbases began with Alder's discovery of 1,8-bis(dimethylamino)naphthalene (DMAN, Figure 1) "proton sponge",13 whose basicity constants were later proposed as thresholds in defining superbases as compounds that are stronger bases than DMAN, corresponding to a gas-phase proton affinity of 245.8 kcal mol–1 and a pKa > 18.6 in acetonitrile.14 DMAN shows highly increased basicity through bidentate-type coordination by the two dimethylamino groups located at the peri-position of the naphthalene skeleton, in spite of consisting of two, normally weakly basic, aromatic tertiary amines. It turned out that such extraordinary basicity is attained by a synergy of two effects, namely (a) destabilization of neutral free base by steric and electrostatic repulsions of the peri-dimethylamino groups, and (b) strong intramolecular hydrogen bonding in the protonated form that relieves repulsions

2


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and stabilizes the system upon protonation. This discovery spurred interest in the area of neutral organic superbases, in particular, promoting a quest to create compounds with the highest basicity.7,8

Figure 1. Basicity of 1,8-bis(dimethylamino)naphthalene.

One of the early approaches to this goal consisted in placing the bulky substituents into positions ortho to the NMe2 groups,15,16 with the idea to bring the peri-nitrogen atoms into an even closer proximity in order to make the resulting base even more destabilized and therefore stronger. Indeed, in several cases this approach turned out to be successful, as, for example, 2,7-dimethoxy derivative is four orders of magnitude more basic than DMAN.17 However, even larger basicities were achieved employing Alder's concept while either changing the naphthalene framework with other carriers or replacing dimethylamino groups with more basic functionalities, including guanidine,1 phosphazene11 and cyclopropenimine groups,18,19 carbenes,20 and most recently the phosphorus ylide moiety as novel carbon bases.21 Most of these systems also rely on the enhanced basicity coming from two or more nitrogen lone pairs forced to be in proximity, while benefiting from at least one intramolecular hydrogen bonding upon protonation. In addition, interesting and promising routes in tailoring highly basic materials were offered by very flexible systems having basic moieties connected either directly through a rotatable single bond,22 or with a flexible methylene linker.23 Such compounds showed increased basicities although lacking favorable effect from the steric interactions in neutral forms, yet being able to fully optimize the cationic hydrogen bonding in conjugate acids, being the predominant reason for their amplified basicity. Furthermore, the 3



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concept of having highly basic molecules that retain a high degree of the flexibility has recently been demonstrated to be beneficial for the selective extraction of the smaller to larger size molecules, as required for the various applications.24 Lastly, in addition to systems owing its increased basicity to multiple hydrogen bonds,25,26 exceptional basicities could be reached using noncovalent interactions to promote the basicity,27–29 which also motivated researchers to recently propose "anion sponges" as close relatives of proton sponges.30,31

As mentioned, a general feature of a large number of organic superbases is the presence of two basic centers placed close to each other and oriented in such a way that the incoming proton forms a stabilizing intramolecular hydrogen bond. Basic centers are usually nitrogen moieties due to their strongly attractive interactions with protons, since nitrogen lone pair orbitals are energetically higher-lying compared to, for example, those of oxygen in ethers and ketones,32 in line with reports that ketones33 and aldehydes34 are less basic than the corresponding imines.35 Still, recently we showed that if one starts with Alder's concept of having two basic nitrogen moieties at peri-1,8 position on naphthalene and introduces two Noxide groups on the other side of the aromatic ring at 4,5 position, one arrives at molecules in which the oxygen basicity of N–oxides surpasses the nitrogen basicity within the same system.36 Moreover, such molecules containing two neighboring N–oxide moieties are several orders of magnitude stronger bases than the analogous nitrogen proton sponges in both gas-phase and acetonitrile.36 We also demonstrated that, contrary to classical proton sponges, the high basicity of such systems is almost entirely a consequence of destabilized neutral bases through the steric repulsions of the two negatively charged oxygen atoms, while only a small contribution is offered by the intramolecular [O–H·····O]– hydrogen bonding in the conjugate acids.36

Prompted by those results, the purpose of the present work is to advance this concept by replacing the Noxide moiety with other pnictogen oxides X–O (X = P, As), and investigate the susceptibility of such 4


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systems towards a proton. Their basicity parameters will be evaluated using DFT B3LYP methodology and implicit SMD solvation in both gas-phase and acetonitrile solution in order to offer guidelines for a successful design of novel superbases with exceptional basicities.

COMPUTATIONAL DETAILS Gas-phase proton affinities (PAs) and basicities (GBs) were calculated as protonation enthalpies and freeenergies, respectively, employing the B3LYP/6–311++G(2df,2pd)//B3LYP/6–31+G(d,p) level of theory, and using the following reaction:

B–H+(gas)  B(gas) + H+(gas)

(1)

where B and B–H+ denote a base in question and its conjugate acid, respectively. Frequency analysis, performed at the B3LYP/6–31+G(d,p) level, was used to calculate thermal corrections and validate the nature of the optimized stationary points. In this way, all thermodynamic values reported here correspond to a room temperature of 298.15 K and a normal pressure of 1 atm. The choice of this methodology was prompted by its demonstrated accuracy in modeling acid/base features of various organic and inorganic systems,7,8,37 and by the fact that it was recently employed to successfully describe aromaticity of benzene and naphthalene upon pnictogen substitution.38

Absolute solution phase pKa values in acetonitrile were calculated from the gas-phase basicities corrected for the solvation free-energies on structures reoptimized with the (SMD)/B3LYP/6–31+G(d,p) model, and utilizing the experimental value of ΔGSOL(H+)MeCN = –254.3 kcal mol–1.39 Atomic charges were obtained by the natural bond orbital (NBO) analysis40 as the single-point calculations at the same level of theory in acetonitrile. All calculations were performed using the Gaussian 09 software.41 5



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RESULTS AND DISCUSSION Molecules studied in this work are depicted in Figure 2 and their choice was motivated by the fact that many aromatic phosphorines and arsinines exist as well as their oxides.38,42 These are selected to allow us to estimate the basicity of the pnictogen-oxide moiety X–O (X = N, P, As) placed within the aromatic naphthalene framework, and to evaluate the effect of the electron-donating dimethylamino, guanidino and phosphazeno groups on the calculated basicities. Their basicity features will be inspected relative to benzene derivatives having one such basic moiety. A general feature of all these systems 5X–8X is the presence of two basic centers in the molecule that are oriented in such a way that the incoming proton can form an intramolecular hydrogen bond. To further test this concept, we also investigated systems in which we replaced the naphthalene scaffold with larger fluorene (9X) and phenanthrene (10X) frameworks, which are likely to bring the basic X–O groups even closer to each other, thus potentially contribute towards the basicity increase. For the latter, we only focused on the substituent effect of the phosphazeno group, since this moiety showed by far the most prominent basicity enhancement effect.

Figure 2. Schematic representation of investigated bases. In the nomenclature used throughout the paper, in the place of X we use the actual pnictogen atom, in other word X = N, P, As for nitrogen, phosphorus and arsenic, respectively.

6


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Evaluated basicity constants are given in Table 1. We calculated both PA and GB values for all investigated systems, and since these two sets are highly correlated, we will discuss only the corresponding PA values. This is justified by the fact that the latter are easier to interpret, while, at the same time, providing a good measure of the basicity in the gas-phase.7,8 All studied compounds are most favorably protonated at the pnictogen-oxide moiety, even in mono-substituted benzenes 1X–4X, in agreement with our previous work.36 Additionally, throughout the text we will discuss geometric and electronic parameters obtained at the acetonitrile solution unless stated otherwise.

Table 1. Calculated Gas Phase Proton Affinities PAs and Basicities GBs (in kcal mol–1), together with pKa Values in Acetonitrile Solution (in pKa units) as Obtained at the B3LYP/6– 311++G(2df,2pd)//B3LYP/6–31+G(d,p) Level of Theory. PA

GB

PA

pKa

GB

pKa

PA

GB

pKa

1N

219.9 212.9

9.8

1P

202.8 196.2 –7.6

1As

219.0 212.5

2N

239.9 232.9 19.9

2P

227.3 220.8 11.4

2As

257.3 251.4 42.4

3N

245.7 238.6 19.8

3P

235.3 228.5 12.0

3As

266.7 260.2 43.5

4N

252.2 245.7 23.4

4P

243.0 235.6 15.6

4As

274.1 267.0 46.8

5N

241.7 233.5 23.3

5P

210.5 203.3 –9.2

5As

228.1 221.5 14.0

6N

264.0 256.9 39.4

6P

242.4 235.3 23.8

6As

275.9 269.6 41.2

7N

279.2 273.1 43.8

7P

253.7 247.7 26.7

7As

286.8 280.9 49.3

8N

291.4 284.6 47.1

8P

265.1 257.8 31.8

8As

298.5 283.0 54.0

9N

292.4 285.7 45.4

9P

261.4 254.3 21.5

9As

292.2 285.4 47.3

10N 291.5 283.4 44.2

10P 268.6 261.9 31.1

8.7

10As 300.5 293.1 54.8

7



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Let us start our discussion with the simplest molecule, pyridine-N-oxide 1N. It is derived from pyridine, yet simple pyridines are known to be stronger solution-phase bases than their N-oxides. This has been experimentally demonstrated for various solvents, as, for example, pKa values of pyridine and 1N are 5.21 and 0.79 (in water),43 11.64 and 9.03 (in acetonitrile),44–46 5.35 and 2.69 (in methanol),45 3.57 and 1.68 (in DMF),47 and 11.54 and 8.55 (in propylene carbonate),48 respectively. Our calculated values of PA(1N) = 219.9 and GB(1N) = 212.9 kcal mol–1 show that this trend is maintained in the gas-phase as well, as 1N is intrinsically a weaker base than pyridine, whose experimental values are PA(pyridine)EXP = 222.0 and GB(pyridine)EXP = 214.7 kcal mol–1,49 with differences of –2.1 and –1.8 kcal mol–1, respectively. In this context, it is worth mentioning that phosphorous analogue 1P is much less basic than 1N, while arsenic analogue 1As only reaches the basicity level of 1N. Still, at this point it is worth emphasizing that calculations for 1N are found in excellent agreement with experimentally determined PA(1N)EXP = 220.7 and GB(1N)EXP = 213.4 kcal mol–1,49 which, together with the fact that our estimate pKa(1N) = 9.8 nicely ties in with pKa(1N)EXP = 9.03,45 lends credence to the computational methodology used here, thus suggesting that other presented results are likely to be reliable.

As a common feature, in neutral forms 1X–4X, all pnictogen–oxygen bonds (X–O) are co-planar with the aromatic ring, only with minor distortions in few cases. However, upon the protonation, the incoming proton is placed perpendicular to the aromatic ring, in agreement with previous reports.50–53 The difference occurs in the X–O bond, which remains co-planar in N-oxides, while, in phosphorus and arsenic derivatives, the protonation twists the aromatic ring at the position of the pnictogen atom and distorts the X–O bond from the plane as well (Figure 3).

8


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2N+

2P+

2As+

6As+

6As

Figure 3. Schematic representation of optimized geometries in acetonitrile solution for some illustrative examples discussed in the text, as obtained with the (SMD)/B3LYP/6–31+G(d,p) model.

Basicity of 1X (X = N, P, As) can be significantly enhanced by introducing strong electron-donating substituents in the para-position in all cases (Table 1). Although utilized dimethylamino, guanidino and phosphazeno moieties are highly basic functionalities on their own,7,8 in 2X–4X the most favorable protonation site remains the pnictogen-oxide group. The basicity increase in these systems is fully in line with the electron-donating ability of the attached substituents, in a way that substituents order as PA(R = H) < PA(R = NMe2) < PA(R = Gv) < PA(R = Pz). This suggests that the latter groups have a role of promoting the pnictogen-oxide basicity by participating in the resonance stabilization, rather than being the site of the H+ attack. Taking N-oxides as an example, the mentioned substitution increases basicity 9



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from 219.9 kcal mol–1 in 1N, over 239.9 kcal mol–1 in 2N and 245.7 kcal mol–1 in 3N, all the way to 252.2 kcal mol–1 in 4N. The latter value demonstrates an exceptional electron-donating ability of the phosphazeno group, which promotes the basicity of 4N by as much as 32.3 kcal mol–1 relative to 1N, which is really impressive for a single substitution. At the same time, 4N is already by 6.4 kcal mol–1 a stronger base than DMAN in the gas-phase and can, therefore, be classified as a superbase.

Analogous phosphorus-oxides 2P–4P also benefit from the mentioned para-substitution, but all systems are consistently weaker bases than the analogous nitrogen derivatives by around 9–13 kcal mol–1. On the other hand, the matching arsenic-oxides 2As–4As turned out to be even more potent bases than their nitrogen-oxide counterparts. The basicity increase assumes 17.4 kcal mol–1 for 2As, increases to 21.0 kcal mol–1 for 3As, and is the highest for 4As being 21.9 kcal mol–1. Combined, here the basicity enhancement of the phosphazeno group assumes huge 55.1 kcal mol–1, which is remarkable indeed. To the best of our knowledge, with PA = 274.1 kcal mol–1 and pKa = 46.8, 4As is the strongest closed-shell neutral organic superbase predicted until now, among simple systems having only one basic functionality and not benefiting from any hydrogen bonding in the conjugate acid.

In order to rationalize the presented trends in basicities, it is useful to inspect the changes in relevant geometries and bond distances induced by protonation. Interestingly, upon protonation, the X–O distances become elongated in all derivatives 1X+–4X+, for example from 1.304 Å in 1N to 1.387 Å in 1N+. Moreover, heavier derivatives undergo even a larger change, from 1.506 Å in 1P to 1.592 Å in 1P+, or from 1.658 Å in 1As to 1.767 Å in 1As+. This trend is consistent with all para-substituents, with an important observation that the elongation of the X–O bond is larger as the basicity is higher. Such geometric change is unexpected, and it comes as a result of a favorable electron density transfer from the aromatic ring to the pnictogen atom. For example, NBO charge analysis reveals that in 1N+ the charge on the incoming proton is only 0.56 |e|, while it changes from –0.62 to –0.56 |e| on the oxygen atom, and 10


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from 0.06 to –0.01 |e| on the nitrogen pnictogen atom. This confirms the strong electron donation to that part of the molecule from the rest of the system, which sums to around 0.57 |e|. In the phosphazeno derivative 4N+, this is even slightly higher as the total charge transfer to this triatomic fragment is 0.60 |e| upon protonation. In 4As+, which is by far the most basic monocyclic system examined here, this is even more significant. There, the charge on the incoming H+ is 0.54 |e|, while it changes from –1.06 to –1.83 |e| on the oxygen atom, and from 1.71 to 1.21 |e| on the arsenic atom, yielding a total of 1.73 |e| being transferred to these three atoms upon protonation, which is remarkable. This supports the idea that the formation of the XO–H+ bond (X = N, P, As) enhances cationic resonance stabilization, which is efficiently utilized by the para-substituents through the electron donation to work towards increased basicities. The latter is clearly evident in the shortening of the matching C–R bonds, where R represents the nitrogen atom of the para-substituent bonded to the ring carbon. Taking most basic 2As–4As as examples, the corresponding C(ring)–N(substituent) distances change from 1.419, 1.398 and 1.384 Å in neutral bases, respectively, to 1.319, 1.302 and 1.303 Å in conjugate acids, in the same order. Taking all together, it follows that in benzene derivatives having a single pnictogen-oxide moiety, the basicity is determined by the efficiency to delocalize an excess positive charge created upon protonation, which is assisted by the strong electron-donating substituents in the para-position.

Let us now switch our attention to systems bearing two pnictogen-oxide moieties at peri-1,8 positions on the naphthalene scaffold. System 5N is already appreciably basic, PA(5N) = 241.7 kcal mol–1, being 21.8 kcal mol–1 more basic than monomeric pyridine N-oxide 1N. The protonation of 5N again occurs on one N-oxide moiety, which then forms hydrogen bonding with the other N-oxide group, which is a motif also evident in other N-oxides 6N–8N as well. Basicity of 5N is dramatically enhanced by attaching substituents to positions 4- and 5- as the calculated PAs (pKas) of 6N–8N assume 264.0 (39.4), 279.2 (43.8) and 291.4 kcal mol–1 (47.1), respectively, spanning an increase of 49.7 kcal mol–1 and 23.7 pKa units, which is significant. To put these numbers into a perspective, let us mention that by making 4,511



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bis(N,N-dimethylamino) substitution on DMAN, yielding 1,4,5,8-tetrakis(dimethylamino)naphthalene, one increases the pKa value in DMSO only by 2.3 units.54 The demonstrated trend is also observed in the peri-phosphorus-oxides 5P–8P, although the protonation of one P–O moiety does not produce any significant hydrogen bonding among basic centers, due to already mentioned twist in the structure around the protonated pnictogen functionality. On the other hand, the other pnictogen moiety remains co-planar with its aromatic ring (Figure 3). In phosphorus systems, one notices even a larger increase on going from the unsubstituted 5P to 4,5-bisphosphazeno derivative 8P, which assumes 54.6 kcal mol–1. Yet, this is still not enough for 8P to exhibit a higher basicity than 8N, nor it is for any 5P–7P relative to 5N–7N, respectively. Completely opposite situation is observed with arsenic-oxides 5As–8As. Although 5As is only moderately basic, and its PA(5As) = 228.1 kcal mol–1 is by 13.6 kcal mol–1 lower than that for 5N, the substitution of 5As with dimethylamino, guanidino and phosphazeno moieties enhances the basicity by 47.8, 58.7, and 70.4 kcal mol–1, making 6As–8As a much stronger bases than 6N–8N. With its PA = 298.5 kcal mol–1, 8As approaches the gas-phase proton affinity of 300 kcal mol–1, proposed as a borderline between superbases and hyperbases.55

In analogy with classical proton sponges, the pronounced basicity of 5X–8X (X = N, P, As) should be a consequence of an interplay of two contributions: (a) strong electron repulsions between two neighboring negatively charged oxygen atoms, which destabilize the initial base, and (b) the formation of a favorable [O–H·····O]– hydrogen bonding, which relieves steric strain and stabilizes conjugate acid. Both contributions could be quantitatively estimated by the following two homodesmotic reactions:56,57

and 12


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OH

O

OH

O

X

X

X

X

+ EHB(nH+) R

R

R

R

R

R

R

R

Here, ESTRAIN(n) gives the steric interference of two basic pnictogen-oxide groups (X–O) in neutral bases with positive values indicating the existence of strain which contributes to basicity, whereas EHB(nH+) denotes the energy of the intramolecular hydrogen bond in conjugate acids with negative values pointing to a stabilizing hydrogen bonding that also improves the basicity. Both sets of data are presented in Table 2 and are calculated as the gas-phase reaction enthalpies in order to be compatible with the discussed differences in the proton affinities (PAs). Let us also mention that the presented equations are designed for systems with the naphthalene scaffold; for the systems with the fluorene and phenathrene scaffolds the corresponding equations are formed in an analogous way.

Table 2. Calculated Energy of the Steric Strain in Neutral Bases (ESTRAIN) and the Energy of the Intramolecular Hydrogen Bond in Conjugate Acids (EHB) as Obtained at the B3LYP/6– 311++G(2df,2pd)//B3LYP/6–31+G(d,p) Level of Theory (in kcal mol–1). ESTRAIN

EHB

ESTRAIN

EHB

ESTRAIN

EHB

5N

19.7

3.6

5P

4.7

1.8

5As

5.1

9.6

6N

20.6

2.1

6P

5.9

1.9

6As

6.7

5.9

7N

21.5

–0.8

7P

6.3

4.5

7As

–5.3

–1.3

8N

22.0

–2.7

8P

2.9

–0.2

8As

–2.3

4.4

9N

17.0

–13.1

9P

6.7

–1.8

9As

6.8

–1.1

10N 12.0

–17.1

10P 10.4

–2.2

10As 4.2

–8.7

13



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It turns out that the calculated strain in naphthalene based peri-N-oxides 5N–8N is large, and is increased in the same order from 19.7 kcal mol–1 in 5N to 22.0 kcal mol–1 in 8N, where it is the largest. This is because the N-oxide groups are not flexible enough, as it is the case with P–O and As–O groups (see later), to more efficiently diminish electrostatic repulsions from the negatively charged oxygen atoms. Distortion of the N-oxide groups from the plane of the aromatic ring follows the trend in the calculated ESTRAIN values, being lowest in 1N (11°) and largest in 4N (22°). Interestingly, these ESTRAIN values are higher than in classical proton sponges. For example, ESTRAIN and EHB contributions in DMAN are 6.1 and –12.8 kcal mol–1,58 respectively. Moreover values for 7N and 8N are even above 21.1 kcal mol–1 recently reported for the 1,8-bis(bis(diiso-propylamino)cyclopropeniminyl) naphthalene,59 suggesting that the steric strain might be the predominant factor leading to the high basicity of 5N–8N. Indeed, the hydrogen bond stabilization, EHB, in 5N+–8N+ is small, even disfavoring protonation in 5N+ and 6N+. This is because, in order to form the HB interaction, the created O–H+ bond must move from its preferred out-of-plane position, as in 1N–4N, to coplanar orientation, which turns out not to be so favorable. In addition, the formed hydrogen bonds are characterized with [O–H·····O]– bonding angles being far from ideal and clustering around 158° in all 5N+–8N+. Such diminished influence of the hydrogen bonding is completely opposite to classical proton sponges, in which this effect is dominant.7,8

Part of the motivation for the current work originates from the idea to replace the naphthalene scaffold with fluorene and phenanthrene in order to bring the basic X–O moieties even closer, thus potentially increase the strain and promote the hydrogen bonding formation. This showed to be only partially true, as the strain energies in 9N and 10N are reduced to 17.0 and 12.0 kcal mol–1, respectively, evident in a much reduced distortion of the N-oxide group, which, for example, in 9N assumes only 9.9°. Nevertheless, this unfavorable reduced impact from the ESTRAIN is overcome by a significant increase in the stability of the formed hydrogen bonding to –13.1 and –17.1 kcal mol–1, in the same order. For example, in 9N+ the hydrogen bonding angle optimizes to 178.4°, which is reflected in the mentioned increase in the EHB 14


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value. Jointly, these two effect contribute around 30 kcal mol–1 to the basicity of 9N and 10N, being much higher than around 22–24 kcal mol–1 found in 5N–8N, thus the higher basicity in the former two systems.

Relative to that, phosphorous and arsenic compounds behave similarly in a way that both contributions are much smaller in comparison to those found for N-oxides. P–O derivatives 5P–10P show moderate strain energy that is only slightly increased in 10P (10.4 kcal mol–1). There, two phosphorus-oxides approach each other at a shortest distances, which is compensated by a very significant distortion of 35°, thus the high ESTRAIN(10P) value. In other phosphorous systems, the distortion assumes between 2°–12°, therefore much lower strain energies in 5P–9P. However, large strain later allows for a more optimal hydrogen bonding, thus the most favorable EHB for 10P (–2.2 kcal mol–1). There, the corresponding [O– H·····O]– distance assumes 1.682 Å (H·····O separation here and throughout the text), while in other P–O derivatives it stretches from 2.026 Å in 9P to 3.011 Å in 7P, thus closely following a trend in the calculated EHB values. All of this is in line with the fact that 10P is the strongest base among studied phosphorous compounds, still significantly less basic than its nitrogen and arsenic alternatives.

Arsenic compounds also reveal reduced strain, which is occasionally even negative, as in 7As and 8As. It is most favorable in 6As and 9As, yet this is not so much reflected in the high basicity as the hydrogen bonding contributions are negligible. This is likely the reason to why 9As shows a significant drop in basicity relative to 8As. On the other hand, the strength of the [O–H·····O]– hydrogen bond exhibits a peak in 10As+ (–8.7 kcal mol–1), which we attribute as being predominantly responsible for the exceptional basicity of this system. There, although a significant distortion of both As–O fragments is evident, being 71.9° in protonated As–OH+ and 58.8° in the other unprotonated As–O moiety, the phenanthrene scaffold allows a proximity of these two fragments close enough for an efficient hydrogen bonding. The corresponding [O–H·····O]– distance assumes 1.530 Å, being by far the shortest such separation in all 5As+–9As+. 15



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It is of significant practical interest to estimate the pKa values of superbases in polar aprotic solvents, exemplified here with the acetonitrile solution (Table 1). For that purpose we reoptimized geometries in the acetonitrile solution using implicit SMD model. Even though we did not observe any significant changes in the resulting structures to those found in the gas-phase, our previous experience in calculating pKa data in various solutions22,23,36 shows that this approach gives somewhat more accurate pKa values than it would by just taking single-point SMD energies on geometries optimized in the gas-phase.

Although there are many factors affecting basicity in liquid media other than the intrinsic basicity,9 such as the size of the molecule, efficiency of the charge delocalization, polarity, etc., it turns out that a trend in the gas-phase basicities is well preserved in acetonitrile too. One notices a very poor basicity of 1P and 5P in solution as evidenced in negative pKa values, suggesting these systems could be protonated only with very strong acids, being in line with their lowest gas-phase basicities. Moreover, systems containing P–O groups are, as a rule, less basic than the corresponding N–O and As–O derivatives in acetonitrile as well. It turns out that the applied strategy in designing novel organic superbases, starting from the corresponding N-oxides and modifying both the basic pnictogen-oxide center and the aromatic scaffold, also worked well in the acetonitrile solution. Systems 8As and 10As are the most potent superbases investigated here in both phases. This clearly demonstrates that replacing peri-N-oxides with peri-Asoxides in naphthalene enables an increase in the pKa value of 6.9 pKa units (8As relative to 8N), while replacing naphthalene with phenanthrene contributes additional 0.8 pKa units (10As relative to 8As). With PA = 300.5 kcal mol–1, the resulting base 10As breaks the hyperbasicity threshold in the gas-phase,55 and reaches a solution-phase basicity off 55 pKa units in acetonitrile, which is really impressive. Therefore, the synthesis of molecule 10As and related derivatives is highly recommended.

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CONCLUSIONS In this work we used DFT B3LYP calculations to demonstrate that pnictogen-oxides provide very basic fragments, especially when placed on the aromatic scaffold and combined with judiciously selected electron-donating substituents. A particular basicity enhancement is achieved when two such basic spearheads are positioned in a close proximity, as in peri-position on the naphthalene ring. Their increased oxygen basicity convincingly surpasses that of related classical nitrogen proton sponges, and was determined to be a consequence of a fine interplay of several factors, including (a) destabilization of neutral bases through the steric repulsions of the two negatively charged oxygen atoms, (b) favorable intramolecular [O–H·····O]– hydrogen bonding in conjugate acids, and (c) efficiency of dispersing an excess positive charge upon protonation. The highest basicity is achieved with the two arsenic-oxide moieties on the phenanthrene framework assisted with the two phosphazeno groups in the para-position to both basic centers. With its proton affinity of PA = 300.5 kcal mol–1, compound 10As breaks the gasphase hyperbasicity threshold of 300 kcal mol–1, while its solution-phase constant approaching pKa = 55 reveals exceptional basicity in acetonitrile as well. Thus, the investigated molecules provide important rungs in the upper part of the superbasicity ladder in both phases, and their synthesis is highly recommended. In addition, the obtained insight provides guidelines in designing even more basic organic materials: one route is offered through finding even more suitable organic scaffolds that could host basic pnictogen-oxides while allowing efficient balance between maximizing strain and optimizing hydrogen bonding formation, whereas the second pathway is given through introducing more than one electrondonating substituent on the available positions on the aromatic skeleton.

Given the growing interest in highly basic compounds together with related basic catalysts and metal complexing agents, we hope that the results presented here would open a new avenue of research in these

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fields and direct the attention towards utilizing aromatic pnictogen-oxides in designing improved organic materials.

ACKNOWLEDGEMENT This work benefited from the financial support from the Croatian Science Foundation through the project grant IP–2014–09–3368. We would like to thank the Zagreb University Computing Centre (SRCE) for granting computational resources on the ISABELLA cluster and the CRO-NGI infrastructure.

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REFERENCES

1

Superbases for Organic Synthesis: Guanidines, Amidines, Phosphazenes and Related Organocatalysts; Ishikawa, T., Ed.; John Wiley & Sons: Chichester, U.K., 2009.

2

Taylor, J. E.; Bull, S. D.; Williams, J. M. Amidines, Isothioureas, and Guanidines as Nucleophilic Catalysts. Chem. Soc. Rev. 2012, 41, 2109−2121.

3

Alonso-Moreno, C.; Antiñolo, A.; Carrillo-Hermosilla, F.; Otero, A. Guanidines: From Classical Approaches to Efficient Catalytic Syntheses. Chem. Soc. Rev. 2014, 43, 3406−3425.

4

Boileau, S.; Illy, N. Activation in Anionic Polymerization: Why Phosphazene Bases are Very Exciting Promoters. Prog. Polym. Sci. 2011, 36, 1132−1151.

5

Gelbard, G.; Vielfaure-Joly, F. Polynitrogen Strong Bases as Immobilized Catalysts. React. Funct. Polym. 2001, 48, 65−74.

6

Ishikawa,T.; Harwood, L. M. Organic Superbases: The Concept at a Glance. Synlett. 2013, 24, 2507-2509.

7

Raczynska, E. D.; Gal, J.-F.; Maria, P. C. Enhanced Basicity of Push–Pull Nitrogen Bases in the Gas Phase. Chem. Rev. 2016, 116, 13454-13511.

8

Maksić, Z. B.; Kovačević, B.; Vianello, R. Advances in Determining the Absolute Proton Affinities of Neutral Organic Molecules in the Gas Phase and Their Interpretation: A Theoretical Account. Chem. Rev. 2012, 112, 5240-5270.

9

Lõkov, M.; S. Tshepelevitsh, S.; Heering, A., Plieger, P. G.; Vianello, R.; Leito, I. On the Basicity of Conjugated Nitrogen Heterocycles in Different Media. Eur. J. Org. Chem. 2017, 30, 4475-4489.

10

Saame, J.; Rodima, T.; Tshepelevitsh, S.; Kütt, A.; Kaljurand, I.; Haljasorg, T.; Koppel, I. A.; Leito, I. Experimental Basicities of Superbasic Phosphonium Ylides and Phosphazenes. J. Org. Chem. 2016, 81, 7349-7361.

19



Page 20 of 26

11

Kaljurand, I.; Saame, J.; Rodima, T.; Koppel, I.; Koppel, I. A.; Kögel, J. F.; Sundermeyer, J.; Köhn, U.; Coles, M. P.; Leito, I. Experimental Basicities of Phosphazene, Guanidinophosphazene, and Proton Sponge Superbases in the Gas Phase and Solution. J. Phys. Chem. A. 2016, 120, 25912604.

12

Kaupmees, K.; Trummal, A.; Leito, I. Basicities of Strong Bases in Water: A Computational Study. Croat. Chem. Acta 2014, 87, 385-395.

13

Alder, R. W.; Bowman, P. S.; Steele, W. R. S.; Winterman, D. P. The Remarkable Basicity of 1,8Bis(dimethylamino)naphthalene. Chem. Commun. 1968, 723–724.

14

Kaljurand, I.; Kütt, A.; Sooväli, L.; Rodima, T.; Mäemets, V.; Leito, I.; Koppel, I. A. Extension of the Self-Consistent Spectrophotometric Basicity Scale in Acetonitrile to a Full Span of 28 pKa Units: Unification of Different Basicity Scales. J. Org. Chem. 2005, 70, 1019-1028.

15

Alder, R.W.; Goode, N.C.; Miller, N.; Hibbert, F.; Hunte, K. P. P.; Robbins, H. J. Extremely Strong but Sluggish Amine Bases. J. Chem. Soc. Chem. Commun. 1978, 9, 89-90.

16

Hibbert, F.; Simpson G. R. Acid-Base Properties of Highly Substituted Diaminonaphthalenes. J. Chem. Soc., Perkin Trans. 2 1987, 2, 243-246.

17

Filatova, E. A.; Pozharskii, A. F.; Gulevskaya, A. V.; Vistorobskii, N. V.; Ozeryanskii, V. A. Synthesis of 2-Alkynyl-, 4-Alkynyl-, and 2,7-Dialkynyl-1,8-bis(dimethylamino)naphthalenes and the Unexpected Influence of ortho-Alkynyl Groups on Their Basicity. Synlett. 2013, 24, 2515-2518.

18

Nacsa, E. D.; Lambert, T. H. Higher-Order Cyclopropenimine Superbases: Direct Neutral Brønsted Base Catalyzed Michael Reactions with α-Aryl Esters. J. Am. Chem. Soc. 2015, 137, 10246–10253.

19

Stukenbroeker, T. S.; Bandar, J. S.; Zhang, X.; Lambert, T. H.; Waymouth, R. M. Cyclopropenimine Superbases: Competitive Initiation Processes in Lactide Polymerization. ACS Macro Lett. 2015, 4, 853–856.

20


Page 21 of 26 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


20

Lo, R.; Ganguly, B. In Silico Studies in Exploiting Weak Noncovalent C–H+···π and π–π

Interactions To Achieve Dual Properties: Hyperbasicity and Multiple Dihydrogen Storage Materials with Paracyclophane-Based Carbene Derivatives. J. Phys. Chem. C. 2013, 117, 19325-19333. 21

Kögel, J. F.; Margetić, D.; Xie, X.; Finger, L. H.; Sundermeyer, J. A. Phosphorus Bisylide: Exploring a New Class of Superbases with Two Interacting Carbon Atoms as Basicity Centers. Angew. Chem. 2017, 56, 3090-3093.

22

Schwamm, R. J.; Vianello, R.; Maršavelski, A.; García, M. A.; Claramunt, R. M.; Alkorta, I.; Saame, J.; Leito, I.; Fitchett, C. M.; Edwards, A. J., et al. 15N NMR Spectroscopy, X-ray and Neutron Diffraction, Quantum-Chemical Calculations, and UV/Vis-Spectrophotometric Titrations as Complementary Techniques for the Analysis of Pyridine-Supported Bicyclic Guanidine Superbases. J. Org. Chem. 2016, 81, 7612–7625.

23

Coles, M. P.; Aragon–Saez, P. J.; Oakley, S. H.; Hitchcock, P. B.; Davidson, M. G.; Maksić, Z. B.; Vianello, R.; Leito, I.; Kaljurand, I.; Apperley, D. C. Superbasicity of a Bis–Guanidino Compound with a Flexible Linker: A Theoretical and Experimental Study. J. Am. Chem. Soc. 2009, 131, 16858–16868.

24

Singh, A.; Ojha, A. K.; Jang, H. M. Strategic Design and Utilization of Molecular Flexibility for Straddling the Application of Organic Superbases: A DFT Study. ChemistrySelect 2018, 3, 837– 842.

25

Bachrach, S. M. Extended Hydrogen Bond Network Enabled Superbases. Org. Lett. 2012, 14, 5598-5601.

26

Tian, Z.; Fattahi, A.; Lis, L.; Kass, S. R. Neutral Intramolecular Hydrogen-Bonded Bases. Croat. Chem. Acta. 2009, 82, 41–45.

21



Page 22 of 26

27

Martín-Fernández, C.; Montero-Campillo, M. M.; Alkorta, I.; Yáñez, M.; Mó, O.; Elguero, J. Large Proton-Affinity Enhancements Triggered by Noncovalent Interactions. Chem. Eur. J., in print. DOI: 10.1002/chem.201705047

28

Gámez, J. A.; Corral, I.; Mó, O.; Yáñez, M. Unexpected Gas-Phase Ion Chemistry Results Unraveled by Computational Chemistry. Curr. Org. Chem. 2010, 14, 1600-1611.

29

Lamsabhi, A. M.; Vallejos, M. M.; Herrera, B.; Mó, O.; Yáñez, M. Effect of Beryllium Bonds on the Keto–Enol Tautomerism of Formamide Derivatives: A Subtle Basicity-Acidity Balance. Theor. Chem. Acc. 2016, 135, 1-9.

30

Brea, O.; Corral, I.; Mó, O.; Yáñez, M.; Alkorta, I.; Elguero, J. Beryllium-Based Anion Sponges: Close Relatives of Proton Sponges. Chem. Eur. J. 2016, 22, 18322-18325.

31

Montero-Campillo, M. M.; Corral, I.; Mó, O.; Yáñez, M.; Alkorta, I.; Elguero, J. Beryllium-Based Fluorenes as Efficient Anion Sponges. Phys. Chem. Chem. Phys. 2017, 19, 23052-23059.

32

Maksić, Z. B.; Vianello, R. Physical Origin of Chemical Phenomena: Interpretation of Acidity, Basicity, and Hydride Affinity by Trichotomy Paradigm. Pure Appl. Chem. 2007, 79, 1003.

33

Despotović, I.; Maksić, Z. B.; Vianello, R. Design of Bronsted Neutral Organic Bases and Superbases by Computational DFT Methods: Cyclic and Polycyclic Quinones and [3]Carbonylradialenes. Eur. J. Org. Chem. 2007, 20, 3402-3413.

34

Despotović, I.; Maksić, Z. B.; Vianello, R. Engineering Neutral Organic Bases and Superbases by Computational DFT Methods - Carbonyl Polyenes. Eur. J. Org. Chem. 2006, 24, 5505-5514.

35

Despotović, I.; Maksić, Z. B.; Vianello, R. Computational Design of Brønsted Neutral Organic Superbases – [3]iminoradialenes and Quinonimines are Important Synthetic Targets. New J. Chem. 2007, 31, 52-62.

36

Despotović, I.; Vianello, R. Engineering Exceptionally Strong Oxygen Superbases with 1,8Diazanaphthalene di-N-Oxides. Chem. Commun. 2014, 50, 10941-10944. 22


Page 23 of 26 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


37

Raczyńska, E. D.; Makowski, M.; Hallmann, M.; Kamińska, B. Geometric and Energetic Consequences of Prototropy for Adenine and its Structural Models – A Review. RSC Adv. 2015, 5, 36587-36604, and references cited therein.

38

Sánchez-Sanz, G. Aromatic Behaviour of Benzene and Naphthalene upon Pnictogen Substitution. Tetrahedron. 2015, 71, 826-839.

39

Fawcett, W. R. The Ionic Work Function and its Role in Estimating Absolute Electrode Potentials. Langmuir. 2008, 24, 9868-9875.

40

Foster, J. P.; Weinhold, F. Natural hybrid orbitals. J. Am. Chem. Soc. 1980, 102, 7211–7218.

41

Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A., et al. Gaussian 09, Revision A.02; Gaussian, Inc.: Wallingford CT, 2009.

42

Chemistry of Heterocyclic Compounds: The Heterocyclic Derivatives of Phosphorus, Arsenic, Antimony and Bismuth; Mann, F. G., Ed.; John Wiley & Sons, 1970.

43

Perrin, D. D. Dissociation Constants of Organic Bases in Aqueous Solutions, Butterworths: London, 1965.

44

Kaljurand, I.; Rodima, T.; Leito, I.; Koppel, I. A.; Schwesinger, R. Self-Consistent Spectrophotometric Basicity Scale in Acetonitrile Covering the Range between Pyridine and DBU. J. Org. Chem. 2000, 65, 6202-6208.

45

Makowski, M.; Kozak, A.; Chmurzyński, L. A Comparison of Basicities of Substituted Pyridines and Pyridine N-Oxides. Polish. J. Chem. 2002, 76, 581-588.

46

Wróbel, R.; Kaczmarczyk R. E.; Chmurzyński, L. Potentiometric Determination of Standard Acidity and Cationic Standard Homoconjugation Constants of Substituted Pyridine N-Oxide Systems in (Acetonitrile + Methanol). J. Chem. Thermodynamics. 1999, 31, 1561-1571.

23



Page 24 of 26

47

Chmurzyński, L.; Warnke, Z. Acid-Base Equilibria of Substituted Pyridine N-Oxides in N,NDimethylformamide and Dimethyl Sulfoxide. Austr. J. Chem. 1993, 46, 185-194.

48

Wawrzynów, A.; Chmurzyński, L. A Comparison of Acid – Base Properties of Substituted Pyridines and their N-Oxides in Propylene Carbonate. J. Chem. Thermodynamics. 1998, 30, 713722.

49

Linstrom, P. J.; Mallard, W. G. Eds., NIST Chemistry WebBook, NIST Standard Reference Database Number 69, National Institute of Standards and Technology, Gaithersburg MD, 20899, http://webbook.nist.gov

50

Makowski, M.; Liwo, A.; Wróbel, R.; Chmurzyński, L. Ab Initio Study of Energetics of Protonation and Hydrogen Bonding of Pyridine N-Oxide and Its Derivatives. J. Phys. Chem. A. 1999, 103, 11104-11108.

51

Butler, M.; Arroyo Mañez, P.; Cabrera, G. M. An Experimental and Computational Study on the Dissociation Behavior of Hydroxypyridine N-Oxides in Atmospheric Pressure Ionization Mass Spectrometry. J. Mass Spectrom. 2010, 45, 536-544.

52

Abraham, M. H.; Honcharova, L.; Rocco, S. A.; Acree, W. E. Jr.; De Fina, K. M. The Lipophilicity and Hydrogen Bond Strength of N-Oxides and Protonated -N-Oxides. New J. Chem. 2011, 35, 930936.

53

Vianello, R. Protonation of Azines and Purines as a Model for the Electrophilic Aromatic Substitution – Rationalization by Triadic Formula. Acta Chim. Slov. 2011, 58, 509-520.

54

Ozeryanskii, V. A.; Vlasenko, M. P; Pozharskii, A. F. "Proton Sponge" Amides: Unusual Chemistry and Conversion into Superbasic 6,7-Bis(Dimethylamino)Perimidines. Tetrahedron. 2013, 69, 1919-1929.

55

Vianello, R.; Maksić, Z. B. Interpretation of Brønsted Acidity by Triadic Paradigm: A G3 Study of Mineral Acids. J. Phys. Chem. A. 2007, 111, 11718-11724. 24


Page 25 of 26 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


56

George, P.; Trachtman, M.; Bock, C. W.;. Brett, A. M. An Alternative Approach to the Problem of Assessing Destabilization Energies (Strain Energies) in Cyclic Hydrocarbons. Tetrahedron. 1976, 32, 317-323.

57

George, P.; Trachtman, M.; Bock, C. W.;. Brett, A. M.Homodesmotic Reactions for the Assessment of Stabilization Energies in Benzenoid and other Conjugated Cyclic Hydrocarbons. J. Chem. Soc. Perkin Trans. 2. 1976, 1222-1227.

58

Raab V.; Gauchenova E.; Merkoulov A.; Harms,K.; Sundermeyer, J.; Kovačević, B.; Maksić, Z. B. 1,8-Bis(hexamethyltriaminophosphazenyl)naphthalene, HMPN: A Superbasic Bisphosphazene "Proton Sponge". J. Am. Chem. Soc. 2005, 127, 15738-15743.

59

Vazdar, K.; Kunetskiy, R.; Saame, J.; Kaupmees, K.; Leito, I.; Jahn, U. Very Strong Organosuperbases Formed by Combining Imidazole and Guanidine Bases: Synthesis, Structure, and Basicity. Angew. Chem. Int. Ed. 2014, 53, 1435-1438.

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