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Aust. J. Chem. 2014, 67, 1056–1062 http://dx.doi.org/10.1071/CH14182

Effect of Intramolecular Hydrogen Bonds on the Gas-Phase Basicity of Guanidines Zoran GlasovacA,B and Mirjana Eckert-MaksicÁ A

Laboratory for Physical-Organic Chemistry, Division of Organic Chemistry and Biochemistry, RuXer Bosˇkovic´ Institute, HR-10000 Zagreb, Croatia. B Corresponding author. Email: [email protected]

Three series of novel trisubstituted guanidines containing at least one hydrogen bond accepting (HBA) group were modelled using B3LYP/6–311þG(2df,p)//B3LYP/6–31G(d) calculations. Their structure was modified by incorporating a variety of different HBA groups covering a wide range of hydrogen bond strengths. Calculated gas-phase basicities (GBs) ranged from 1035 to 1181 kJ mol1 depending on the nature of the substituent. To rationalise changes in the GB, a correlation of GB against two independent variables (pKHB and s4B) was conducted where pKHB served as the descriptor of the hydrogen bond strength and s4B was introduced to describe changes in the GBs in the open-chain model systems, i.e. in the absence of intramolecular hydrogen bond (IMHB), caused by the electronic effect of the propyl-HBA substituent. A very good correlation of the calculated gas-phase basicities against these two independent variables was established for all three sets of the bases. Manuscript received: 29 March 2014. Manuscript accepted: 8 May 2014. Published online: 12 June 2014.

Introduction Intramolecular hydrogen bond (IMHB) has been recognised as an important building block in the design of neutral organic superbases[1–5] since the discovery of the archetypal ‘Proton spongeÒ’[6] in the late 1960s of the past century. Besides structurally rigid superbases, high gas-phase basicity of simple alkyl diamines,[7–11] aminoalcohols,[7,11] and even arginine[12,13] has been attributed to formation of the rather strong IMHBs upon protonation. Furthermore, Raczyn´ska and Gal found that the gas-phase basicity (GB) of amidines and guanidines depends on both the nature of the hydrogen bond acceptor (HBA) and the ring size formed upon establishing IMHB.[14,15] They measured GBs of 1030–1056 kJ mol1 for a set of tetramethyl and tetraethyl guanidines containing methoxy or dimethylamino group as a HBA and either ethyl or propyl chain as a spacer. A particularly revealing approach was introduced by Maksic´ and coworkers who designed novel guanidines, cyclopropenimines, and other superbasic systems by introducing multiple substituents capable of forming IMHBs which act cooperatively to enhance the gas-phase proton affinities.[3,16,17] Based on the concept of multiple IMHBs, Margetic´[2] proposed a new guanidine base bearing three 2-(4-imidazolyl)propyl substituents with the estimated proton affinity (PA) of 1151 kJ mol1, while Coles, Maksic´ and coworkers[18] calculated a PA of 1130 kJ mol1 for the methylene-N,N0 -bis-(1,5,7triazabicyclo[4.4.0]dec-1-ene). Some of these theoretical results were subsequently confirmed by the gas-phase basicity measurements.[19,20] Recently, Baric´ et al. designed a set of guanidine bases in silico with gas-phase PAs of up to 1227 kJ mol1 using various hydrogen bond accepting groups (HBA groups), such as urea, guanidine, phosphinoxide, phosphoramide, and Journal compilation Ó CSIRO 2014

phosphazene, separated from guanidine by a pentyl group.[21] This brief overview clearly illustrates that the existing basicity scale in the region of superbases could be filled up and even extended merely by changing the strength of IMHB. Hydrogen bonding between guanidines and other functional groups has also been found in organocatalysis where catalytic complex formation can have crucial impact on the reaction rate, outcome, and stereoselectivity if chiral guanidine is employed as the catalyst.[2,22,23] It is reasonable to assume that the presence of IMHB in guanidine catalyst can obscure the formation of such hydrogen-bonded catalytic complexes. Therefore, investigation of the hydrogen bonding in guanidine derivatives is of considerable importance for the rational design of novel organocatalysts where IMHB can be used to increase the basicity of the catalyst without affecting formation of the catalytic complex. The understanding of the intrinsic (gas-phase) properties of such guanidine derivatives represents the first step in that direction. The strength of the IMHBs in aforementioned guanidine derivatives strongly depends on the nature of the hydrogen bond acceptor and hydrogen bond donor. For instance, taking 3-dimethylaminopropyl substituted guanidines and their 3-methoxypropyl counterparts as an example, we note that the former are more basic and exhibit more pronounced increase in GB along with a higher number of substituents capable of forming IMHB.[19,20] To establish the connection between these results and the structure of the base, various theoretical[24–30] and experimental[31–33] descriptors for the intra- and intermolecular hydrogen bonds could be used. In a recent work, we tried to correlate literature known pKHB values with experimentally determined GBs for some N2-heteroalkyl- and N2-2(2-pyridyl)ethyl)- substituted N1,N3-diisopropylguanidines.[19] www.publish.csiro.au/journals/ajc

Gas-Phase Basicity of Guanidines

1057

N R1

N H

X

DMG: R1 Me DMG: R1 i -Pr

NH

TRIS: R1(CH2)3X

R1

18 X H

X 3

2

sp HB acceptors

sp HB acceptors carbonyl oxygen

1 N(CH3)2

O

7

2 OCH3

N CH3

3 SCH3 8

N

CH3

CH3

O S

S

10

pyridines

12

2–(C5H4N)

13

2–(p–NO2C5H3N)

14

2–(p–CNC5H3N)

15

2–(p–CH3OC5H3N)

16

2–(p–(CH3)2NC5H3N)

17

2–(p–(CH2)4NC5H3N)

CH3 N

O

CH3

9

O O

6

N

O

4 P(O)(CH3)2 5

imidazoles CH3

N

N

11 CH3

Chart 1. Schematic representation of the structures of all investigated guanidine bases. Compound numbering was done by combining the guanidine substructure identifier (e.g. DMG) with the number representing a specific HBA group (1–17) or hydrogen atom (18) attached to the propylene spacer.

It was shown that a good correlation exists between GB and pKHB values of the heteroalkyl substituent that were taken from the tabulated values for the most similar neutral molecule. As this work included only a limited set of bases, we thought it would be worth examining whether such a correlation holds for guanidine bases containing a wide variety of HBA groups and if it is possible to use known pKHB(HBA) values to predict GB or hydrogen bond energy (DEHB) of structurally similar and yet unknown guanidine bases. For this purpose, we computationally designed trisubstituted guanidine bases 1–17 containing at least one propyl chain with a hydrogen bond accepting (HBA) group at the terminal position. The other substituents attached to the guanidine subunit encompassed methyl, isopropyl, or two propyl-HBA chains. As a result, the GB values were tuned by the change in electronic effects of the alkyl substituents and by multiple IMHB. The choice of the HBA groups was made by matching to specific pKHB values[32] to ensure systematic change in the hydrogen bond energies (DEHB) and their contribution to the gas-phase basicity. Experimental Computational Details The optimisation of geometries was carried out using the Gaussian03 suite of programs[34] employing the density functional theory hybrid functional B3LYP[35–38] in conjunction with the 6–31G(d) basis set. The minima on the Born– Oppenheimer potential energy surface were confirmed to be true minima by a vibrational analysis. The resulting frequencies were also used to calculate zero-point energies, thermal corrections for enthalpies, and entropies without any scaling or corrections for internal or hindered rotations. Refinement of the electronic energies was carried out by single-point calculations at B3LYP/6–311þG(2df,p)//B3LYP/6–31G(d) level of theory. Geometries of the optimised structures were generated and visualised by MOLDEN 5.0.[39] The gas-phase basicities of the investigated molecules were calculated as the difference in Gibbs energies between neutral guanidines and their protonated forms. Analogously, proton affinities (PAs) were calculated as

the difference in enthalpies of the base–conjugated acid pair. In both cases, appropriate contributions of the proton and work term were included in the calculations. Results and Discussion Three series of novel trisubstituted guanidines bearing one (DMG and DIG series) or three (TRIS series) substituents incorporating hydrogen bond accepting subunit were fully optimised. HBA groups were chosen from the published pKHB values to cover a broad range from 0.16 to 3.5 pKHB units.[32] The model compounds were grouped according to the nature of the heteroatom engaged in hydrogen bonding into two main groups: sp3-hybridised (DMG:1–DMG:6 and their DIG and TRIS analogues) and sp2-hybridised (all other bases). In sulfone, sulfoxide, and phosphinoxide HBA groups, the oxygen atom was also considered to be sp3-hybridised because the S–O and P–O bonds are strongly polarised with bond orders being lower than 2.[40,41] The selected HBA groups used in all three series are listed in Chart 1. It should be noted that owing to flexibility of the chains in all studied bases and their protonated forms, several conformers can exist. Based on previous studies,[16] IMHB in this type of species can be established in two ways forming larger 8- or 9membered cycle (1,3-HB, c1, and c2 in Fig. 1) being mutually different only in dihedral angles within the propylene spacer or by forming smaller 6- or 7-membered cycle (ipso-HB, c3 in Fig. 1).[16,21] The larger 8-membered ring is preferred in e.g. TRIS:1H1, as evidenced by the crystal structure of its hexafluorophosphate salt.[42] However, in most of the compounds calculated here, IMHB is incorporated in a 7- or 9-membered cycle, and determining which of them is preferable is not straightforward. Therefore, we optimised three different hydrogen-bonded conformations of the five selected acid–base pairs, involving 9-membered (c1, c2) and 7-membered (c3) rings, with HBA groups being pyridine, N-methylimidazole, dimethylamido, phosphinoxide, or sulfone substructure. Calculated relative enthalpy (Hrel) values for these selected examples in a DMG series are shown in Fig. 1. Also included are the

1058

Z. Glasovac and M. Eckert-Maksic´

c1

c2

c3

oc

H rel [kJ mol–1] DMG:4

5.7 (0.0)

0.0 (1.1)

7.5 (0.8)

15.5 (61.7)

DMG:6

5.6 (0.0)

0.0 (2.7)

8.7 (2.9)

8.2 (40.0)

DMG:8

0.0 (0.0)

1.2 (6.3)

4.7 (3.5)

12.1 (51.2)

DMG:11

4.4 (7.6)

0.0 (0.0)

4.5 (8.2)

7.7 (49.6)

DMG:12

5.4 (6.8)

0.0 (0.0)

8.6 (7.2)

5.8 (39.6)

Fig. 1. Relative enthalpy (Hrel) values for three different optimised hydrogen-bonded and ‘open-chain’ conformations (c1–c3 and oc) of the five selected base–conjugated acid pairs in the DMG series; relative enthalpies for conjugate acids are given in parentheses. The considered conformations are exemplified by corresponding structures of DMG:8.

relevant data for the ‘open-chain’ (unfolded) conformer (oc) in which IMHB does not exist. The latter structure was used as the reference structure for a rough estimation of the hydrogen bond energies.[16] Enthalpies of all three conformers fall within 10 kJ mol1 and it is therefore expected that all of them contribute to the energy of the system. However, c3 conformer was not identified as the most stable one in either of the tested structures. To simplify further discussion, only the lowest energy geometry of each structure will be considered. Consequently, for the remaining molecules, we optimised only c1 and c2 conformers for each of the compounds and the lower energy structure was used for the GB calculations. In addition, for all the species, the energy of the ‘open-chain’ conformer (denoted with a suffix ‘_oc’ after the compound number) was calculated. Calculated gas-phase basicities (GBs) for all three sets of studied guanidine bases and their ‘open-chain‘ analogues are summarised in Table 1 whereas their PAs are listed in Tables S1–S6 (Supplementary Material). GB values for the DMG series range from 1035 to 1087 kJ mol1 and the PAs were estimated to fall between 1069 and 1119 kJ mol1. As the applied calculation method is known to overestimate GB values by ,10 kJ mol1, the latter need to be appropriately scaled.[19] The obtained GB values of the most basic derivatives DMG:17 and DMG:11 are 1078 and 1072 kJ mol1, respectively that are comparable with the recently measured GBs of N1,N3-bis-(3-dimethylaminopropyl)-N2-propyland N,N0 ,N00 -tris-(2-(2-pyridyl)ethyl)-guanidine.[19] Scaled values calculated for all studied molecules are given in the Supplementary Material (Tables S1, S3, and S5). However, for further discussion on the substituent effects and the hydrogen bonding energies, we shall use the unscaled GBs because it is not possible to estimate the appropriate scaling factors for the open-chain structures and therefore using the scaled GBs would lead to inconsistencies in the results. Going from the dimethylguanidine (DMG) to diisopropylguanidine (DIG) series of bases, GBs values increase by 1–13 kJ mol1 depending on the structure of the HBA unit (Table 1) that is in good agreement with the recently obtained experimental data

for N1,N3-dimethyl- and N1,N3-diisopropyl-N2-2-(2-pyridyl) ethylguanidine (DGB ¼ 8 kJ mol1).[19] Interestingly, the lowest increase in GBs upon replacement of the methyl with the isopropyl groups was encountered for DMG:15–DMG:17 with high pKHB(HBA) values. In these three molecules, the HBA group is pyridine with a strong electron-donating group in the para position which allows effective stabilisation of the conjugate acid through the IMHB, thus reducing the sensitivity of the guanidinium moiety towards the replacement of the alkyl groups. On the other hand, in the case of DMG:13 and DMG:14 in which the pyridine subunit contains electronwithdrawing substituents in the para position, a larger increase in GB (7 kJ mol1) upon replacement of the methyl with the isopropyl group is observed. The gas-phase basicities of the TRIS series of guanidines were calculated to lie above 1100 kJ mol1 for most of the examined bases. Among them, the most basic compound is predicted to be TRIS:17 with p-pyrrolidinylpyridine as HBA group with a GB of 1181 kJ mol1 (1138 kJ mol1 if scaled as commented above) that is comparable with the basicity of recently published bisimidazolyden-guanidine bases.[44] It should be also noted that even TRIS:13, with the lowest GB in this series, is more basic than the well-known commercially available bicyclic base MTBD by ,15 kJ mol1. Calculated hydrogen bond energies (DEHB) of the TRIS derivatives are significantly larger than those of their DMG and DIG analogues as expected due to cooperative action of three IMHBs. Specifically, the observed increase in the GB values is in the range of 16 (for TRIS:13) to 93 (for TRIS:17) kJ mol1 when compared with the DMG counterparts. This is almost a 10-fold stronger effect than observed upon replacement of the methyl with the propyl group. More precisely, in the TRIS series, DEHB contributes ,5–10 % to the GB, as compared with contributions of 2–4 % and 1–4 % for DMG and DIG groups of bases, respectively. It is also important to note that 4-pyrrolidinylpyridine HBA has a strong impact on the GB in the ‘open-chain’ series. For example, incorporation of two additional propyl-HBA substituents on going from DMG:17_oc to TRIS:17_oc causes


1059

Molecule (M) S:1 S:2

S ¼ DMG

S ¼ DIG

S ¼ TRIS

D D pKHB(X)C GB(M) DED HB GB(M) DEHB GB(M) DEHB

2.17 1.00

S:3

0.16

S:4

3.53

S:5

2.54

S:6

1.10

S:7

1.17

S:8

2.44

S:9

2.61

S:10

2.72

S:11

2.72

S:12

1.86

S:13

(0.85)E

S:14

0.92

S:15

2.13

S:16

2.80

S:17

2.93

S:18

–

1051 (1025) 1039 (1020) 1035 (1017) 1066 (1021) 1048 (1013) 1036 (1006) 1047 (1022) 1066 (1030) 1070 (1034) 1069 (1036) 1081 (1041) 1062 (1031) 1036 (1011) 1039 (1013) 1071 (1035) 1083 (1043) 1087 (1045) (1024)

29 23 21 46 38 32 31 39 41 44 42 34 27 28 37 43 44

1056 (1041) 1051 (1038) 1044 (1034) 1073 (1035) 1059 (1028) 1046 (1024) 1059 (1036) 1079 (1041) 1081 (1048) 1078 (1050) 1091 (1054) 1067 (1043) 1044 (1023) 1046 (1027) 1074 (1049) 1085 (1056) 1088 (1054) (1040)

22 16 14 41 33 25 27 35 37 38 41 28 22 23 31 36 37

1098 (1046) 1076 (1023) 1060 (1024) 1142 (1035) 1104 (1014) 1063 (999) 1105 (1028) 1144 (1054) 1153 (1063) 1155 (1073) 1155 (1083) 1116 (1059) 1053 (1015) 1058 (1017) 1137 (1062) 1171 (1079) 1181 (1098) (1042)

71

1100

GB [kJ mol–1]

Table 1. pKHB of the HBA groups, gas-phase basicities (GB), and hydrogen bond energies (DEHB) of the hydrogen-bonded and ‘open-chain’ conformers of the series of N2-substituted-N1,N3-dimethylguanidine (DMG) calculated at B3LYP/6-3111G(2df,p)//B3LYP/6-31G (d) level of theoryA,B

DMG:12 – DMG:17

1090

DMG:7 – DMG:9

1080

DMG:1 – DMG:6

1070

DMG:10 – DMG:11

12

7

1050

M –D

3

4

8

D

1

1040

9 11 10

17

G:

: MG

1060

5

y 9.164x 1029.6 R 2 0.903

6

1030 2

1020

53

y 24.130x 1016.9 R 2 0.994

0

1

2

3

4

pKHB 46 116 103 78 85 106 110 98 92 75 57 58 82 99 97

All energies are given in kJ mol1. Values in parentheses are related to the ‘open-chain’ systems. C For a definition of X, see Chart 1. All pKHB values were taken from Ref. [32] D DEHB ¼ PA(M) – PA(M_oc). E Value is derived from Taft’s relationship between pKHB and substituent constants for the pyridine set of bases (see Supplementary Material).[43] A B

an increase in GB by 53 kJ mol1. Generally, the DGB(DMGTRIS) in the ‘open-chain’ series range from 7 to 53 kJ mol1. Substituent Effects on the Gas-Phase Basicity As mentioned in the Introduction section, our main goal in this work was to examine whether a simple relationship between the gas-phase basicity or hydrogen bond energy and the structure of the bases exist. In 1969, Taft and co-workers showed that a good correlation between pKa(BHþ)H2O and pKHB(B) holds for the structurally related bases (pyridines, primary amines, and carbonyl compounds).[31,32] Although pKHB parameters were developed for a description of intermolecular hydrogen bonding, our recent results[19] indicated that the same data could be used for our set of bases with IMHB. To the best of our

Fig. 2. Correlation between GB(DMG) and pKHB of the various hydrogen bond accepting groups.

knowledge, to date, no other work dealing with comparison of pKHB with acid–base properties has been conducted on molecules with intramolecular hydrogen bonding neither in the gas phase nor in solution. Three sets of the proposed guanidine bases represent suitable samples for further testing the GB–pKHB linear relationship. Since the published pKHB values refer to measurements conducted in CCl4 where little or no specific solvent–solute interactions could be expected, we decided to use these values in combination with the gas-phase basicities and hydrogen bond energies. The resulting correlations between the GBcalc (calculated gas-phase basicities) and pKHB values for the DMG series of bases is presented in Fig. 2, whereas the corresponding plots for the DIG and TRIS series are shown in Figs S2 and S3 in the Supplementary Material. Analysis of the correlations shown in Fig. 2 reveals that only pyridine derivatives DMG:12–DMG:17 follow a linear trend, with satisfactory correlation parameters. On the other hand, GB values for compounds DMG:1–DMG:6 poorly correlate with pKHB that is not surprising because they encompass mutually dissimilar HBA groups. Furthermore, data of the carbonyl analogues DMG:7–DMG:9 lie significantly above the latter regression line being closer to the data corresponding to pyridines. The same trends were also observed in the plots derived from the data of the bases belonging to the DIG and TRIS series. The influence of the substituents on the properties and reactivity has been usually interpreted using Hammet’s s parameters or their variants parameterised byTaft.[43] Although originally developed for derivatives of benzoic acids, they were successfully applied to describe the effect of substituent attached directly to the (de)protonation centre.[45,46] Raczyn´ska and Gal showed that the GBs of a series of phenylamidines and phenyltetramethylguanidines correlate well with Taft’s substituent polarisation effect.[14] As in our case, because HBA groups are attached to the guanidine unit via propyl chain, we assumed that the electronic effect of the entire propyl-HBA group would be more appropriate for discussing changes in basicities. Only few s parameters describing the effect of the substituted alkyl groups have been published to date, none of which include substituted propyl chains.[43] To circumvent this problem, we decided to introduce a new parameter, denoted as s4B (Eqn 1), which describes a change in the proton affinity of the considered ‘open-chain’ conformers with respect to the propyl derivative DMG:18. The calculated change in PAs in the ‘open-chain’ analogues is solely caused by the electronic effects of the propyl-HBA groups without any contribution from IMHB. s4B ðHBAÞ ¼ PAcalc ðM ocÞ PAcalc ðS : 18Þ

ð1Þ


σ4B(HBA)DIG

1060

25

Table 2. Statistical data obtained by correlation according to Eqn 1 for the three series of the guanidine basesA

20 15 10 5

20

10

DGB(M) [kJ mol1]

y 0.898x 0.57 R 2 0.993

Molecule (M)

0 5

10

0

20

30

σ4B(HBA)DMG

10 15 20

Fig. 3. Correlation between s4B structural parameters evaluated for the DMG and DIG series of compounds. 1100

GBcalc [kJ mol–1]

1090 1080 1070

y 8.02x 1039.6 R 2 0.975

1060 1050 DMG:1

1040 DMG:2

1030 2

1

S:1 S:2 S:3 S:4 S:5 S:6 S:7 S:8 S:9 S:10 S:11 S:12 S:13 S:14 S:15 S:16 S:17 MUEB a b c R2

s4B

S ¼ DMG

S ¼ DIG

S ¼ TRIS

0.59 2.87 2.98 6.27 10.71 17.40 1.80 7.76 11.06 6.76 18.17 7.21 11.19 9.86 12.60 19.65 21.98

7 6 0 1 1 5 0 1 1 1 1 0 1 2 2 1 2 2 8.02 1.00 1039.58 0.975

10 2 0 1 0 5 3 4 3 3 5 2 2 1 1 3 2 2 8.02 0.86 1047.9 0.948

19 5 6 1 1 8 17 7 6 13 10 6 8 7 3 1 3 6 24.21 2.01 1062.9 0.956

1020 0

1

2

3

pKHB (b/a)

4

5

6

7

σ4B

Fig. 4. Correlation between GB calculated for the DMG series of bases and two independent variables, pKHB and s4B.

The same approach was then applied to calculate the s4B parameters for the other two sets of bases (DIG and TRIS series). The s4B values obtained for these three groups of guanidine derivatives correlate well mutually as exemplified for s4B(HBA)DMG and s4B(HBA)DIG in Fig. 3. The slope of the line shown in Fig. 4 is lower than 1, indicating smaller impact of the substituents on the GB values across the DIG:X_oc than in DMG:X_oc series. It appears that the isopropyl groups, which amplify basicity through polarisation effects,[43] concurrently attenuate the influence of the HBA group replacement on the GB. A similar trend was obtained for the correlation of s4B(HBA)DMG and s4B(HBA)TRIS, with a slope of 2.413, intercept of 0.315, and R2 of 0.990. This in turn implies that the effect of the substituents on the GB in the TRIS series is larger than in the DMG series of bases as expected owing to the presence of three equivalent HBA-substituted propyl chains. Incidentally, the above-mentioned slope of 2.4 is lower than the expected value of 3, indicating even stronger attenuation of the influence of the HBA group replacement than in the DIG series. Based on the good correlation between s4B parameters obtained for all three series of bases, we decided to use the s4B values calculated for the DMG set of molecules as the second independent variable in the correlation between GB(M) and (pKHB; s4B) for all three series of the investigated bases according to Eqn 2: GBðMÞ ¼ a pKHB ðHBAÞ þ b s4B ðHBAÞ þ c where M stands for DMG, DIG, or TRIS.

ð2Þ

pKHB values are given in Table 1; DGB values represent deviation of the calculated GBs from the correlation line. The statistical data are given for the correlations obtained in the presence of outlying points. B MUE ¼ mean unsigned error. A

Correlation between GB(DMG) and the two independent variables resulted in a linear relationship with a regression coefficient R2 of 0.975 (Fig. 4). Also, no clustering of the bases with structurally similar HBA groups into separate subgroups was observed. Only three bases (DMG:1, DMG:2, and DMG:6) were found to deviate significantly from the correlation line. Upon removal of these outliers, R2 increases to 0.996. It could also be noted that the slope and the intercept are very similar to the previously published GB–pKHB correlation of five measured N2-substituted-N1,N3-diisopropylguanidines.[19] The analogous correlations were also conducted for DIG and TRIS series (Figs S4 and S5 in the Supplementary Material) and the resulting statistical data are summarised in Table 2. Usage of s4B parameters with other two series resulted in graphs with somewhat larger scattering of the data than in the DMG case. 3-Dimethylaminopropyl derivatives (DIG:1 and TRIS:1) appeared to be particularly problematic cases, with data points located away from the regression line. It should also be noted that in the DIG and TRIS series, carbonyl-containing bases were positioned above the correlation line. This holds in particular for TRIS:7 which deviates by 17 kJ mol1 from the correlation line and therefore this base was removed from the correlation. After removal of the aforementioned outliers, the regression coefficients for these two series increased from 0.948 (0.956) to 0.972 (0.978) where the data obtained for the TRIS series are given in parentheses. A similar correlation was obtained when PAs were used instead of GB values (Fig. S6 in the Supplementary Material). We assume that larger scattering of the data observed for the DIG and TRIS series could be at least partially ascribed to steric effects.


1061

(a) 50.0

substituent on the PA of unfolded bases. Combining this parameter with pKHB resulted in a very good correlation with GB for all three groups of guanidine bases possessing intramolecular hydrogen bond with only one or two strong off-liners. In addition, hydrogen bond energy (DEHB) was better correlated against pKHB without s4B contribution although some HBA structure-dependent scattering was observed for the TRIS derivatives.

ΔE HB(DMG) [kJ mol–1]

45.0 40.0 35.0 30.0 25.0 20.0

Pyridines and imidazoles

15.0

Carbonyls

10.0

S–O and P–O

5.0

Supplementary Material

Sulfide, amine and ether

0 0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

pK HB

ΔE HB(TRIS) [kJ mol–1]

(b) 140.0 120.0 100.0

Carbonyls

80.0

Pyridines

S–O and P–O

Acknowledgements

60.0

Pyridines and imidazoles

40.0

Carbonyls

20.0

S–O and P–O Sulfide, amine and ether

0 0

0.5

1.0

Calculated energy data of the lowest energy conformers for all hydrogen-bonded and open-chain structures, PAs, scaled GBs, plots of the GBs against pKHB or two independent variables (pKHB and s4B) for the DIG and TRIS series, and Cartesian coordinates for all optimised minima are available on the Journal’s website.

1.5

2.0

2.5

3.0

3.5

4.0

pK HB Fig. 5. Correlation between hydrogen bond energies (DEHB) and pKHB for the (a) DMG and (b) TRIS series of bases.

Finally, we also examined the correlation between DEHB and pKHB for all three series of bases and the results are presented in Fig. 5. Analysis of the data shows that in the case of DMG derivatives, a linear trend with a good regression coefficient (R2 ¼ 0.966) was attained, but only when DMG:1 and DMG:2 were omitted from the correlation. The plot of DEHB against pKHB for the DIG series (see Fig. S7 in the Supplementary Material) resulted in slightly more pronounced scattering (R2 ¼ 0.941), whereas for the TRIS group of bases (Fig. 5b), a strong dependence on the structure of the HBA groups was observed. Using s4B parameters in conjunction with pKHB did not improve the correlations but rather had the opposite effect. In this case, separate correlation lines for different families of bases were found (Fig. S8 in the Supplementary Material). Conclusion Three series of the strong neutral organic bases based on guanidine subunit were modelled using B3LYP/6–311þG(2df,p)// B3LYP/6–31G(d) level of theory and their gas-phase basicities were calculated to lie above 1000 kJ mol1, with the most basic derivatives being in the range of 1150–1190 kJ mol1. Contribution of intramolecular hydrogen bond energy (DEHB) to the basicity was determined as the difference between PA values of the lowest energy hydrogen bonded structures and their ‘open-chain’ analogues providing strong variation of the GB values (i.e. up to 130 kJ mol1). Both GB and DEHB values were correlated against pKHB that was used as the descriptor of the IMHB strength, and a satisfactory correlation was obtained only for a series of derivatives containing pyridine HBA groups. To take into account structural diversity of the hydrogen bond accepting (HBA) groups in our systems, we introduced a s4B parameter that describes the effect of the HBA-containing

Support from the Ministry of Science, Education and Sports of Croatia (Project No. 098–0982933–2920) and the Croatian Academy of Science and Arts (HAZU project ‘Polyfunctional guanidines: Design, synthesis, and catalytic properties of novel superbases’) are gratefully acknowledged. We would also like to thank the Computing Center of the University of Zagreb (SRCE) for allocation of computer time on the Isabella cluster. We thank Dr Davor Margetic´ for calculation of GB of N-methylimidazole derivative TRIS:11.

References [1] R. W. Alder, Chem. Rev. 1989, 89, 1215. doi:10.1021/CR00095A015 [2] D. Margetic´, in Superbases for Organic Synthesis (Ed. T. Ishikawa) 2009, Ch. 2, pp. 9–48 (John Wiley and Sons, Ltd: Chichester). For the reviews on usage of superbases in organocatalysis, see also other chapters. [3] Z. B. Maksic´, B. Kovacˇevic´, R. Vianello, Chem. Rev. 2012, 112, 5240. doi:10.1021/CR100458V [4] (a) M. Meot-Ner (Mautner), Chem. Rev. 2005, 105, 213. doi:10.1021/ CR9411785 (b) M. Meot-Ner (Mautner), Chem. Rev. 2012, 112, PR22. doi:10.1021/CR200430N [5] J. Sundermeyer, V. Raab, E. Gaoutchenova, U. Garrelts, N. Abacilar, K. Harms, in Activating Unreactive Substrates: The Role of Secondary Interactions (Eds C. Bolm, F. E. Hahn) 2009, Ch. 2, pp. 17–37 (WileyVCH Verlag GmbH & Co. KGaA: Weinheim). [6] R. W. Alder, P. S. Bowman, W. R. S. Steele, D. R. Winterman, Chem. Commun. 1968, 723. doi:10.1039/C19680000723 [7] G. Bouchoux, J.-Y. Salpin, Mass Spectrom. Rev. 2012, 31, 353. doi:10.1002/MAS.20343 [8] E.-I. Roõ˜m, A. Ku¨tt, I. Kaljurand, I. Koppel, I. Leito, I. A. Koppel, M. Mishima, K. Goto, Y. Miyahara, Chem. –Eur. J. 2007, 13, 7631. doi:10.1002/CHEM.200700097 [9] G. Bouchoux, D.-A. Buisson, Int. J. Mass Spectrom. 2006, 249–250, 412. doi:10.1016/J.IJMS.2005.11.023 [10] R. Yamdagni, P. Kebarle, J. Am. Chem. Soc. 1973, 95, 3504. doi:10.1021/JA00792A010 [11] M. Meot-Ner, P. Hamlet, E. P. Hunter, F. H. Field, J. Am. Chem. Soc. 1980, 102, 6393. doi:10.1021/JA00534A019 [12] G. Bouchoux, Mass Spectrom. Rev. 2012, 31, 391. doi:10.1002/MAS. 20349 [13] G. Bouchoux, S. Desaphy, S. Bourcier, C. Malosse, R. N. Biboum Bimbong, J. Phys. Chem. B 2008, 112, 3410. doi:10.1021/JP709677C [14] E. D. Raczyn´ska, M. Decouzon, J.-F. Gal, P.-C. Maria, G. Gelbard, F. Vielfaure-Joly, J. Phys. Org. Chem. 2001, 14, 25. doi:10.1002/10991395(200101)14:1,25::AID-POC332.3.0.CO;2-E [15] M. Decouzon, J.-F. Gal, P.-C. Maria, E. D. Raczyn´ska, Rapid Commun. Mass Spectrom. 1993, 7, 599. doi:10.1002/RCM.1290070708

1062

[16] B. Kovacˇevic´, Z. Glasovac, Z. B. Maksic´, J. Phys. Org. Chem. 2002, 15, 765. doi:10.1002/POC.552 [17] Z. Gattin, B. Kovacˇevic´, Z. B. Maksic´, Eur. J. Org. Chem. 2005, 3206. doi:10.1002/EJOC.200500054 [18] M. P. Coles, P. J. Aragoń-Saéz, S. H. Oakley, P. B. Hitchcock, M. G. Davidson, Z. B. Maksic´, R. Vianello, I. Leito, I. Kaljurand, D. C. Apperley, J. Am. Chem. Soc. 2009, 131, 16858. doi:10.1021/ JA906618G [19] Z. Glasovac, F. Pavosˇevic´, V. Sˇtrukil, M. Eckert-Maksic´, M. Schlangen, R. Kretschmer, Int. J. Mass Spectrom. 2013, 354–355, 113. doi:10.1016/J.IJMS.2013.06.012 [20] Z. Glasovac, V. Sˇtrukil, M. Eckert-Maksic´, D. Schro¨der, M. Kaczorowska, H. Schwarz, Int. J. Mass Spectrom. 2008, 270, 39. doi:10.1016/J.IJMS.2007.11.008 [21] D. Baric´, I. Dragicˇevic´, B. Kovacˇevic´, J. Org. Chem. 2013, 78, 4075. doi:10.1021/JO400396D [22] P. Selig, Synthesis 2013, 45, 703. doi:10.1055/S-0032-1318154 [23] D. Leow, C.-H. Tan, Synlett 2010, 1589. doi:10.1055/S-0029-1219937 [24] S. Grabowski, Hydrogen Bonding – New Insights 2006 (Springer: Dodrecht). [25] S. J. Grabowski, Chem. Rev. 2011, 111, 2597. doi:10.1021/ CR800346F [26] R. W. F. Bader, Atoms in Molecules: A Quantum Theory 1997 (Oxford University Press: New York, NY). [27] A. J. Green, P. L. A. Popelier, J. Chem. Inf. Model. 2014, 54, 553. doi:10.1021/CI400657C [28] S. J. Grabowski, J. Phys. Org. Chem. 2004, 17, 18. doi:10.1002/ POC.685 [29] S. J. Grabowski, Chem. Phys. Lett. 2001, 338, 361. doi:10.1016/ S0009-2614(01)00265-2 [30] A. E. Reed, L. A. Curtiss, F. Weinhold, Chem. Rev. 1988, 88, 899. doi:10.1021/CR00088A005 [31] R. W. Taft, D. Gurka, L. Joris, P. von R. Schleyer, J. W. Rakshys, J. Am. Chem. Soc. 1969, 91, 4801. doi:10.1021/JA01045A038 [32] C. Laurence, J. F. Gal, Lewis Basicity and Affinity Scales: Data and Measurements 2010, Ch. 4, pp. 111–227 and the references therein (John Wiley and Sons, Ltd: Chichester). [33] M. H. Abraham, J. Phys. Org. Chem. 1993, 6, 660. doi:10.1002/POC. 610061204 [34] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, J. A. Montgomery, Jr, T. Vreven, K. N. Kudin,


[35] [36] [37] [38] [39] [40] [41] [42] [43] [44] [45] [46]

J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, C. Gonzalez, J. A. Pople, Gaussian 03, Revision D.02 2003 (Gaussian Inc.: Wallingford, CT). A. D. Becke, J. Chem. Phys. 1993, 98, 5648. doi:10.1063/1.464913 C. Lee, W. Yang, R. G. Parr, Phys. Rev. B 1988, 37, 785. doi:10.1103/ PHYSREVB.37.785 B. Miehlich, A. Savin, H. Stoll, H. Preuss, Chem. Phys. Lett. 1989, 157, 200. doi:10.1016/0009-2614(89)87234-3 P. J. Stephens, F. J. Devlin, C. F. Chabalowski, M. J. J. Frisch, J. Phys. Chem. 1994, 98, 11623. doi:10.1021/J100096A001 G. Schaftenaar, J. H. Nordik, J. Comput. Aided Mol. Des. 2000, 14, 123. doi:10.1023/A:1008193805436 D. B. Chesnut, L. D. Quin, J. Comput. Chem. 2004, 25, 734. doi:10.1002/JCC.20003 D. B. Chesnut, A. Savin, J. Am. Chem. Soc. 1999, 121, 2335. doi:10.1021/JA984314M Z. Glasovac, B. Kovacˇevic´, E. Mesˇtrovic´, M. Eckert-Maksic´, Tetrahedron Lett. 2005, 46, 8733. doi:10.1016/J.TETLET.2005.10.035 C. Hansch, A. Leo, R. W. Taft, Chem. Rev. 1991, 91, 165. doi:10.1021/ CR00002A004 K. Vazdar, R. Kunetskiy, J. Saame, K. Kaupmees, I. Leito, U. Jahn, Angew. Chem. Int. Ed. 2014, 53, 1435. doi:10.1002/ANIE.201307212 R. A. L. Peerboom, L. J. de Koning, N. M. M. Nibbering, J. Am. Soc. Mass Spectrom. 1994, 5, 159. doi:10.1016/1044-0305(94)85029-1 M. Eckert-Maksic´, Z. Glasovac, J. Phys. Org. Chem. 2005, 18, 763. doi:10.1002/POC.930