Broadband Microwave Spectroscopy of Prototypical Amino Alcohols

Article pubs.acs.org/JPCA

Broadband Microwave Spectroscopy of Prototypical Amino Alcohols and Polyamines: Competition between H‑Bonded Cycles and Chains Di Zhang,† Sebastian Bocklitz,‡ and Timothy S. Zwier*,† †

Department of Chemistry, Purdue University, West Lafayette, Indiana 47907-2084, United States Institut für Physikalische Chemie, Universität Göttingen, 37077 Göttingen, Germany

‡

S Supporting Information *

ABSTRACT: The rotational spectra of the amino alcohols D-allo-threoninol, 2-amino1,3-propanediol, and 1,3-diamino-2-propanol and the triamine analog, propane-1,2,3triamine, have been investigated under jet-cooled conditions over the 7.5−18.5 GHz frequency range using chirped-pulsed Fourier transform microwave spectroscopy. Microwave transitions due to three conformers of D-allothreoninol, four conformers of 2-amino-1,3-propanediol, four conformers of 1,3-diamino-2-propanol, and four conformers of propane-1,2,3-triamine have been identified and assigned, aided by comparison of the fitted experimental rotational constants with the predictions for candidate structures based on an exhaustive conformational search using force field, ab initio and DFT methods. Distinctions between conformers with similar rotational constants were made on the basis of the observed nuclear quadrupole splittings and relative line strengths, which reflect the direction of the permanent dipole moment of the conformers. With three adjacent H-bonding substituents along the alkyl chain involving a combination of OH and NH2 groups, hydrogen-bonded cycles (3 H-bonds) and chains (2 H-bonds) remain close in energy, no matter what the OH/NH2 composition. Two families of H-bonded chains are possible, with Hbonding substituents forming curved chain or extended chain structures. Percent populations of the observed conformers were extracted from the relative intensities of their microwave spectra, which compare favorably with relative energies calculated at the B2PLYP-D3BJ/aug-cc-pVTZ level of theory. In glycerol (3 OH), D-allothreoninol (2 OH, 1 NH2), 2-amino-1,3-propanediol (2 OH, 1 NH2), and 1,3-diamino-2-propanol (1 OH, 2 NH2), H-bonded cycles are most highly populated, followed by curved chains (3 OH or 2 OH/1 NH2) or extended chains (1 OH/2 NH2). In propane-1,2,3-triamine (3 NH2), H-bonded cycles are pushed higher in energy than both curved and extended chains, which carry all the observed population. The NH2 group serves as a better H-bond acceptor than donor, as is evidenced by optimized structures in which H-bond lengths fall into the following order: r(OH···N) ≈ r(OH···O) < r(NH···N) ≈ r(NH···O).

I. INTRODUCTION Amino alcohols and their derivatives are widely used in organic synthesis and medicinal chemistry. Reduced from a chiral pool such as the L-amino acids, β-amino alcohols serve as chiral auxiliaries or ligands for asymmetric catalysis.1 Various amino alcohol derivatives also exhibit antimicrobial2 and antifungal3 activity. As a result, the amino alcohol group has been adopted in several antibiotics, including ethambutol4 prescribed for treatment of tuberculosis and other infections. With a combination of amino and hydroxyl functional groups distributed along an alkyl chain, the amino alcohols can engage in intramolecular H-bonds that dictate the conformational preferences of the molecules. One useful strategy for probing the hydrogen-bonding architecture of conformationally flexible molecules is to study them in isolated form in the gas phase, where supersonic expansion can be used to collisionally cool the sample, thereby trapping the population in the low-lying conformational minima where the conformations can be interrogated by a range of spectroscopic methods.5−7 When the molecule of interest incorporates a UV chromophore, IR/ UV double resonance methods can provide single conformation © 2015 American Chemical Society

IR spectra that report directly on the hydrogen bonding architecture via the hydride stretch fundamentals.8 However, they require the presence of an aromatic chromophore, and provide less detailed structural characterization than might be ideal. Chirped-pulse Fourier transform microwave spectroscopy (CP-FTMW)9 is a powerful alternative for the assignment and structural determination of different conformational isomers in the gas phase. It allows for the acquisition of broadband spectra at high resolution of molecules that possess permanent dipole moments. Moreover, the intensities of the rotational transitions can be related in a straightforward way to the relative populations. Thus, it is a well suited technique to examine the conformational properties of the small amino alcohol molecules in the gas phase. In a recent study from our group,10 CP-FTMW spectroscopy was used to determine the conformational preferences of a first Received: October 30, 2015 Revised: December 9, 2015 Published: December 10, 2015 55

DOI: 10.1021/acs.jpca.5b10650 J. Phys. Chem. A 2016, 120, 55−67

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The Journal of Physical Chemistry A

included on the basis of harmonic vibrational frequency calculations. The experimental methods for the CP-FTMW measurements have been described in detail elsewhere.22 Briefly, the solid sample was wrapped in cotton and inserted into a stainless steel sample holder that was heated to ∼130 °C to obtain sufficient vapor pressure and entrained in neon carrier gas at a backing pressure of 0.7 bar. The sample holder was located immediately behind a pulsed valve (Parker General Valve, Series 9) with a 1 mm diameter nozzle orifice, operating at 10 Hz. One microsecond long frequency-chirped microwave pulses spanning the 7.5−18.5 GHz range interrogated the jetcooled molecules. Upon interaction with the microwave field, a macroscopic polarization was induced in the sample, and a 20 μs free induction decay (FID) was collected and down converted for display and processing on a 12 GHz digital oscilloscope operating at a sampling rate of 40 GS/s. A total of 10 000 free-induction decays (FIDs) were averaged in the time domain, both with (signal + background) and without (background only) spectra. Limited sample sizes, especially for propane-1,2,3-triamine, prevented longer averages. The background contains resonances arising from reflecting surfaces in the chamber, which were identified and removed from the spectrum. Two related methods were employed to extract relative populations of the observed conformers from the microwave spectra. Intensities of transitions were tabulated without an attempt to normalize for changes in microwave power with frequency.9 A simple, approximate method employed in previous work,23 involved taking the sum of the intensities of each type of microwave transition (a-, b-, or c-type) for a given conformer (e.g., conformer X), dividing by the square of the associated component of the dipole moment squared, and summing:

amino alcohol, D-threoninol. With functional groups on three adjacent alkyl carbons (one NH2 and two OH groups), cooperative hydrogen-bonded networks could be formed, with examples of both cyclic and chain structures represented. In what follows, we expand our study of the amino alcohols to include D-allothreoninol, 2-amino-1,3-propanediol, and 1,3diamino-2-propanol, and supplement these studies with the triamine analog 1,2,3-triamino propane. D-Allothreoninol is a diastereomer of D-threoninol, differing in the chirality at a single site. In the other two, the terminal methyl group is removed to simplify the potential energy surface. In so doing, it is possible to concentrate more directly on the changes induced by the position and number of NH2/OH groups along the alkyl chain.

This series has as its trialcohol analog glycerol, HOCH2− CH(OH)−CH2OH, whose microwave spectrum was recently studied in detail by Ilyushin et al.11 The three adjacent OH sites in glycerol are reminiscent of the sugars.12 As we shall see, the molecules in our series have low-energy conformers that form both H-bonded chains and cycles, much as occurs in glycerol. As a result, we can compare and contrast the ways in which the chains and cycles compete with one another as a function of OH/NH2 makeup.

II. EXPERIMENTAL AND COMPUTATIONAL METHODS To identify the possible conformational minima associated with each molecule in the series, an exhaustive conformational search was carried out using the Amber* force field in the MACROMODEL13 suite of programs. Depending on the molecule, anywhere from 20 to 100 structures were found within the 50 kJ/mol energy window prescribed for the search. These structures served as starting geometries for full optimizations using ab initio and density functional theory (DFT) calculations via the Gaussian 09 suite of programs.14 For initial structure prediction, optimizations were carried out at the MP2/6-311++G(d,p) level of theory. Rotational constants at this level of theory have been shown in previous work to be in close agreement with experiment.15 Although this level of theory is useful for structure determination, the calculated energies are known to contain significant basis set superposition error.16 Therefore, further calculations were carried out, using the redefined structures of the MP2/6-311++G(d,p) method as starting point, for further optimization and energy determination. MP2/aug-cc-pVTZ calculations explored the effects of increasing the basis set on the MP2 energies. DFT calculations employing the B3LYP17 or M05-2X18 hybrid functionals, or B2PLYP19 double-hybrid functional, all with the aug-cc-pVTZ basis set, provided a range of methods between which relative energies could be compared. Dispersion correction from Grimme and co-workers with Becke−Johnson dampening was added to the B3LYP and B2PLYP calculations.19,20 Both of these levels of theory were shown to give good results for the relative energies in a recent study of monoglyme (CH3OCH2CH2OCH3), a molecule similar in size to the aminoalcohols of interest here.21 Also, the M05-2X hybrid functional has performed well in predicting relative energies in previous work.18 Tight convergence criteria were employed, and zero-point energy corrections were

PXα

∑i Ia(i) μa

2

+

∑j Ib(j) μb

2

+

∑k Ic(k) μc 2

Alternatively, a least-squares fit to the microwave spectra for each conformer was obtained by first varying the temperature to obtain a best-fit temperature (Trot = 1.5 K), and then extracting the relative population of each conformer from the normalization constants for each conformer obtained from the best-fit. The two methods yielded similar percentage populations, consistent with estimated errors of about ±5% on these percentages.

III. RESULTS AND ANALYSIS A. Nomenclature. Despite the small size of these molecules, with three adjacent hydrogen bonding substitutents involving a combination of OH and NH2 groups, several different combinations of H-bonding architecture (e.g., cycle versus chain) and backbone dihedral angles are possible. In each case, about 10 different conformations of each molecule are predicted to have energies within 500 cm−1 of the global minimum. D-Allothreoninol (2S,3R), is a diastereomer of Dthreoninol (2S, 3S). The other amino alcohols and the triamine all lack the terminal methyl group present in threoninol, giving them greater symmetry and eliminating one of the chiral centers. Nevertheless, a similar nomenclature to the one used for D-threoninol,10 which is adapted from one that is often employed for small aliphatic amino acids, was used here. 56


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The Journal of Physical Chemistry A Two examples are shown below for 2-amino-1,3-propanediol. After rotating the molecules so that as many heavy atoms as possible are placed above the plane of an upside-down Vshaped carbon framework, the substituents are listed as α-OH, β-NH2, and γ −OH from left to right. Roman numerals I, II, and III denote the direction of the H-bonds along the carbon framework, α → β → γ (I), γ → β → α (II), and γ → α → β (III). A subscript (2 or 3) is then used to denote the number of the intramolecular hydrogen bonds within the molecule, 2 for H-bonded chains and 3 for H-bonded cycles. Finally, the dihedral angles between adjacent heavy atom substituents are given in parentheses, with angles within ±10° of +60° and −60° labeled as gauche (g+ and g−, respectively) whereas those in the range between ±90° and 180° are labeled anti (a). The dihedral angle between Oα and Nβ is listed first, whereas that for Nβ with respect to Oγ is listed second. Similar bonding patterns are also present in propane-1,2,3triamine and 1,3-diamino-2 propanol. In propane-1,2,3triamine, because the β(NH2) has two hydrogen bond donors, a unique H-bonding pattern (labeled IV) is possible in which the β amine donates both to α and γ substituents, α(NH2) ← β(NH2) → γ(NH2). Finally, in 1,3-diamino-2-propanol, several structures with only a single H-bond were also predicted within 500 cm−1 of the global minimum. However, as we shall see, these structures were higher in energy, and not observed in the supersonic expansion. Finally, it is worth noting that the three propyl derivatives that form the main sequence studied here (2-amino-1,3propanediol, 1,3-diamino-2-propanol, and propane-1,2,3-triamine) are all symmetric, and thus have two identical minima on the potential energy surface related by reflection of the standard configuration through a vertical plane. This changes I3(g−g+) into II3(g+g−). In principle, tunneling can interconvert these minima, but in practice, no such tunneling splittings were observed. Because all minima of these molecules come in such identical pairs, the relative populations are unaffected by their presence.

Figure 1. (a) Experimental rotational spectrum of jet-cooled Dallothreoninol from 7.5 to 18.5 GHz. (b) Close-up of the 15.85−15.95 GHz region with calculated stick spectra due to conformer A (red), B (blue), and C (green) below, showing the quality of the fit. (c) Further expansion of 5 MHz regions around the 322−212 transitions of conformers A, C are shown in (b), to compare the experimental and calculated nuclear quadrupolar splittings for the two assigned cyclic conformers. The F′−F″ labels are included in the figure.

program26 to refine the rotational constants and expand the number of fitted transitions. Transitions due to three conformers were identified in the spectrum, with calculated stick spectra for the three shown in red (conformer A), blue (conformer B), and green (conformer C) below the experimental spectrum. The number of fitted transitions N, the average standard deviation for each fit (σ), and the resulting sets of fitted rotational constants (A, B, C), and inertial defect (Δ) are listed in Table 2. For the range of rotational transitions observed, centrifugal distortion constants provided only marginally better fits with experiment, and so are not included in the table. Figure 1b includes an expanded view of the 15.85− 15.95 GHz region, demonstrating the quality of the fit. The three assigned conformers for D-allothreoninol are all near-prolate asymmetric tops with the Ray’s asymmetry parameter κ = (2B − A − C)/(A − C)27 lying between −0.5 and −0.8. Two of them have similar κ values around −0.6, and the third one has κ = −0.75, indicating two different structural classes based on the dihedral angles between adjacent heavy atom substituents. Compared with calculation, structures II and III in Table 1 have κ values around −0.6, a value consistent with a g+g− configuration. A κ near −0.75 is consistent with any of the structures I, IV, and V, which all share a g−g− configuration, or structure VIII with its g+g+ configuration. Structures with similar κ values typically also have similar rotational constants because they share the same heavy atom configuration. For example, the experimental rotational constants for structures II and III in the g+g− family are 3132, 2180, and 1920 MHz and 3167, 2129, and 1920 MHz, respectively. These differences are not large enough to discriminate between them on the basis of rotational constants alone.

B. Microwave Spectra. 1. D-Allothreoninol. The experimental microwave spectrum of D-allothreoninol over the range of 7.5−18.5 GHz is presented in Figure 1a. With hundreds of lines observed with a range of intensities, we anticipate that, as in the case of D-threoninol, separate contributions from different conformers will contribute to the spectrum. Because each conformer exhibits a unique pattern of lines, transitions from each are intermingled with one other. To analyze the spectrum, we focused attention on the nine predicted lowest energy conformers within 500 cm−1 of the global minimum, as summarized in Table 1. The calculated rotational constants for these conformers were used as a starting point in providing predictions for the rotational spectrum, using a semirigid rotor Hamiltonian.24 The resulting spectrum was then plotted using the JB95 software developed by Plusquellic25 as a visualization and analysis tool. Tentative assignments were made on the basis of the close match-up of several strong lines in the spectrum. These experimental frequencies were then put into Pickett’s SPFIT/SPCAT 57


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Table 1. Calculated Rotational Parameters and Relative Energies of the Nine Most Stable Confirmations of D-Allothreoninol

a

Calculated rotational parameters at the MP2/6-311++G(d,p) level of theory. Rotational constants at the B2PLYP-D3BJ/aug-cc-pVTZ level of theory are also included after the slash (/). bCalculated relative energies (cm−1) at the B2PLYP-D3BJ/aug-cc-pVTZ level of theory, including harmonic zero-point energy correction.

Conclusive evidence for structural assignments comes from the different 14N nuclear quadrupole splitting patterns, which are produced by the interaction between the nuclear spin angular momentum I (I = 1 for 14N) and the electric field gradient created by the rest of the molecule at the site of each nucleus. Figure 1c shows 5 MHz regions around the 322−212 rotational transitions of the two g+g− conformers, and compares the experimental nuclear quadrupolar splittings with those calculated for the assigned structures of the two cyclic isomers. The patterns are different enough to make a clear assignment for conformer A as structure II, the II3(g+g−) conformer, whereas conformer C is assigned to structure III, the I3(g+g−) conformer. This fitting procedure determines a set of nuclear quadrupole coupling constants χ, which are very sensitive to the orientation of −NH2 group with respect to the principal inertial axis system.28 The fitted values for χ for the assigned conformers are listed in Table 2 and match nicely with those predicted by the ab initio calculations. Structures I and IV have similar quadrupole coupling constants due to the similar orientations of the amino group in these two conformations. To distinguish between them, we

Table 2. Experimental Rotational Parameters of the Three Assigned Conformers of D-Allothreoninol

a Errors in parentheses are expressed in units of the last digit. bNumber of fitted lines, including nuclear hyperfine components. cStandard deviation of the fit.

Table 3. Calculated Rotational Parameters and Relative Energies of the Eight Most Stable Confirmations of 2-Amino-1,3propanediol

A (MHz)a B (MHz) C (MHz) μa (D) μb (D) μc (D) μT (D) χaa (MHz) χbb (MHz) χcc (MHz) κ ΔE (cm−1)b

I (B)

II (A)

III (C)

IV

V (D)

VI

VII

VIII

I2(g−g−)

I3(g−g+)

II2(g−g−)

II2(g+g+)

II2(g−g+)

II2(g−g−)

III2(g−a)

II2(g−g+)

6083/6103 2279/2268 1997/1988 −1.7 0.3 0.9 1.9 −0.29 2.64 −2.36 −0.86 0

4242/4224 3134/3146 2550/2549 0.3 2.7 1.7 3.2 −2.87 1.69 1.18 −0.31 55

5996/6017 2273/2263 1977/1973 4.4 0.9 1.4 4.7 −4.67 2.75 1.91 −0.85 204

6042/6058 2258/2251 1983/1979 1.2 1.4 3.2 3.7 −0.66 2.67 −2.02 −0.86 139

7735/7727 1977/1975 1699/1695 3.5 −1.1 1.8 4.1 −3.94 1.79 2.16 −0.91 201

6033/6009 2235/2239 1951/1954 2.0 0.1 0.9 2.2 −4.48 2.79 1.69 −0.86 264

4173/4239 31673015 2196/2137 2.1 2.2 0.6 3.1 2.15 0.17 −2.32 −0.02 400

7642/76622 1952/1950 1686/1681 1.9 −0.5 −0.1 2.1 −3.83 1.81 2.02 −0.91 304

a

Calculated rotational parameters at the MP2/6-311++G(d,p) level of theory. Rotational constants at the B2PLYP-D3BJ/aug-cc-pVTZ level of theory are also included after the slash (/). bCalculated relative energies (cm−1) at the B2PLYP-D3BJ/aug-cc-pVTZ level of theory, including harmonic zero-point energy correction. 58


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the carbon framework. As a result, Ray’s asymmetry parameter gains in importance over the dihedral angles of the functional groups as a means of grouping them into different structural classes. For 2-amino 1,3 propanediol, the predicted rotational constants and asymmetry parameters for the eight lowest energy structures are summarized in Table 3, with κ values ranging between −0.02 and −0.91. Conformers fall into subgroups around four characteristic κ values (κ = −0.02, −0.3, −0.85, −0.91), with the κ = −0.91 family characteristic of the most extended structures, whereas κ = −0.02 family is most compact. When compared with the experimentally derived κ values, a clear assignment for conformer A to structure II, I3(g−g+), can be made, because it is the only one of the low-energy structures with κ values around −0.3. Conformer D is fit with rotational constants that give a κ = −0.91. Two κ = −0.91 conformers, structure V and structure VIII, are labeled as II2(g−g+), as they are extended H-bonded chains, possessing similar rotational constants, dipole moment projections, and nuclear quadrupole coupling constants. A close look at their structures reveals that they are related to each other by a rotation of the free α(OH) group in the chain structure. Comparing the measured percent populations with calculated relative energies (Table 9), we find that structure V is favored as the structure observed for conformer D. The fact that we see only one of these structures suggests the possibility that conformational interconversion may be happening during the collisional cooling in the expansion. We will consider this possibility further in the Discussion. There are two observed conformers (B and C) with κ = −0.85, and four calculated structures in this category to choose from (structures I, III, IV and VI). Conformer B is unambiguously assigned to structure I through a comparison calculated and experimental quadrupole coupling constants and electric dipole moments. Conformer C is then assigned to structure III over structure VI, which differ once again only in the orientation of the free α(OH) group in the chain structure. Exactly analogous arguments are used to assign conformer C to

make use of the direction of the dipole moment in the molecular frame, whose projections on the inertial axes determine the relative intensities of the a-, b-, and c-type microwave transitions in the spectrum. The rotational spectrum of conformer B shows strong a-type, medium strength c-type, and relatively weak b-type transitions. These data are consistent with the assignment of conformer B as structure I, which is predicted to have μa > μc > μb. C-type transitions are predicted to be strongest in structure IV, counter to experiment. Thus, we assign conformer B to structure I, labeled as II2(g−g−). 2. 2-Amino-1,3-propanediol, 1,3-Diamino-2-propanol, and Propane-1,2,3-triamine. Similar procedures were followed in arriving at assignments for the rotational spectra of 2-amino1,3-propanediol, 1,3-diamino-2-propanol, and propane-1,2,3triamine molecules, respectively. The results are summarized in Tables 3−8. These molecules possess higher symmetry than DTable 4. Experimental Rotational Parameters for the Assigned Conformers of 2-Amino-1,3-propanediol A (MHz) B (MHz) C (MHz) Δ (kHz) χaa (MHz) χbb (MHz) χcc (MHz) Nb σc/kHz κ μa:μb:μc

conformer A

conformer B

conformer C

conformer D

a

6049.922(1) 2265.006(3) 1981.188(4) 0.33(8) −0.31(3)

5981.55(7) 2257.073(1) 1965.833(9) 0.32(3) −3.93(2)

7679.43(7) 1968.92(9) 1689.01(1) −3.23(9)

1.22(3)

2.35(4)

2.28(6)

1.64(4)

1.14(3) 20 5.5 −0.28 b>c>a

−2.03(4) 15 15.2 −0.86 a>c>b

1.64(6) 13 4.4 −0.85 a>c>b

1.59(4) 9 3.1 −0.91 a>c>b

4208.577(8) 3130.694(1) 2527.345(1) 0.59(7) −2.37(2)

a

Errors in parentheses are expressed in units of the last digit. bNumber of fitted lines, including nuclear hyperfine components. cStandard deviation of the fit.

threoninol and D-allothreoninol molecules because the methyl group at the end of the threoninol structure is removed from

Table 5. Calculated Rotational Parameters of the Eight Most Stable Confirmations of 1,3-Diamino-2-propanol

A (MHz)a B (MHz) C (MHz) μa (D) μb (D) μc (D) μT (D) N1χaa (MHz) N1χbb (MHz) N1χcc (MHz) N5χaa (MHz) N5χbb (MHz) N5χcc (MHz) κ ΔE (cm−1)b

I (A)

II (C)

III (B)

IV (D)

V

VI

VII

VIII

II3(g−g+)

I2(g+g−)

II2(g+g−)

I2(g−g−)

S(g+ anti)

I2(g+g+)

I2(g+g+)

S(anti g+)

4314/4323 3019/3002 2488/2480 0.3 1.9 1.7 2.6 −1.99 −0.35 2.34 2.17 −0.52 −1.65 −0.42 0

8073/8071 1969/1969 1711/1707 −2.1 −2.3 0.5 3.1 2.39 −4.55 2.16 2.92 2.24 −5.16 −0.92 112

8062/8053 1947/1948 1695/1692 3.3 −1.7 1.5 4.0 −1.93 0.72 1.21 2.39 −4.58 2.18 −0.92 95

6132/6119 2239/2211 1981/1960 −3.3 −2.4 0.7 4.1 2.79 −3.98 1.19 −4.95 2.28 2.67 −0.88 239

5633/5640 2279/2269 1764/1758 −0.3 −2.2 0.5 2.3 −0.04 −2.19 2.23 2.42 −4.83 −2.41 −0.73 405

6209/6228 2219/2214 1968/1965 −2.4 −2.9 −0.9 3.8 1.61 −2.22 0.61 1.89 2.44 −4.33 −0.88 405

6103/6135 2206/2200 1962/1959 −2.8 −1.7 1.2 3.5 1.59 −2.14 0.55 0.69 −1.08 0.39 −0.88 377

4303/4484 2889/2729 2117/2061 1.4 −2.1 0.2 2.6 1.63 −1.71 0.08 0.97 −3.35 2.38 −0.29 490

a

Calculated rotational parameters at the MP2/6-311++G(d,p) level of theory. Rotational constants at the B2PLYP-D3BJ/aug-cc-pVTZ level of theory are also included after the slash (/). bCalculated relative energies (cm−1) at the B2PLYP-D3BJ/aug-cc-pVTZ level of theory, including harmonic zero-point energy correction. 59


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The Journal of Physical Chemistry A Table 6. Experimental Rotational Parameters for the Four Assigned Conformers of 1,3-Diamino-2-propanol A (MHz) B (MHz) C (MHz) Δ (kHz) N1χaa (MHz) N1χbb (MHz) N1χcc (MHz) N5χaa (MHz) N5χbb (MHz) N5χcc (MHz) Nb σc/kHz κ μa:μb:μc

A

B

C

D

4304.640(5)a 2985.145(8) 2465.185(1) 0.71(5) −1.66(7) −0.35(7) 2.01(7) 1.79(7) −0.45(8) −1.34(8) 11 10.7 −0.43 b>c>a

7983.566(2) 1941.489(2) 1687.348(2) 1.68(1) −1.55(6) 0.73(7) 0.81(7) 2.09(3) −3.73(4) 1.64(4) 21 15.9 −0.92 a>b>c

8000.795(8) 1961.541(9) 1701.152(5) 0.25(2) 2.14(3) −3.78(3) 1.64(3) 2.57(4) 1.79(4) −4.37(4) 17 9.6 −0.92 b>a>c

6056.698(1) 2250.505(9) 1996.815(1) 1.77(5) 2.16(5) −3.19(5) 1.03(5) −4.37(1) 2.19(1) 2.18(1) 13 14.5 −0.88 a>b>c

a Errors in parentheses are expressed in units of the last digit. bNumber of fitted lines, including nuclear hyperfine components. cStandard deviation of the fit.

Table 7. Calculated Rotational Parameters of the Eight Most Stable Confirmations of Propane-1,2,3-triamine

A (MHz)a B (MHz) C (MHz) μa (D) μb (D) μc (D) μT (D) N1χaa (MHz) N1χbb (MHz) N1χcc (MHz) N3χaa (MHz) N3χbb (MHz) N3χcc (MHz) N5χaa (MHz) N5χbb (MHz) N5χcc (MHz) κ ΔE (cm−1)b

I(A)

II(B)

III

IV(C)

V

VI(D)

VII

II2(g+g+)

IV2(g−g+)

II3(g−g+)

II2(g−g−)

I2(g−g+)

II2(g−g+)

I2(g+g+)

5805/5810 2259/2240 1969/1950 0.4 0.1 1.8 1.9 2.51 −3.65 1.15 −0.43 2.32 −1.88 0.62 −2.47 1.86 −0.85 0

7575/7518 1929/1924 1686/1680 0 −2.6 1.6 3.0 2.31 −4.37 2.06 1.64 2.59 −4.24 2.31 −4.37 2.06 −0.92 64

4143/4126 3007/2988 2452/2428 0.1 −0.1 1.4 1.4 1.71 −0.18 −1.52 −3.59 2.01 1.58 −1.82 −0.28 2.10 −0.34 201

5837/5814 2227/2219 1930/1919 2.5 −1.1 0.1 2.8 1.69 −1.63 −0.06 −3.68 2.41 1.27 2.23 1.75 −3.98 −0.85 221

7405/7356 1945/1939 1688/1682 −1.7 −1.6 1.6 2.8 2.60 1.42 −4.02 −2.64 1.19 1.44 2.35 −4.24 1.89 −0.91 171

7393/7346 1920/1915 1669/1664 −2.9 −1.4 0.5 3.3 2.35 −4.27 1.92 −2.39 1.15 1.24 −1.42 0.84 0.59 −0.91 188

5729/5716 2218/2208 1924/1912 −2.9 −0.0 2.0 3.6 0.99 −1.21 0.22 −3.78 2.35 1.43 1.65 −1.49 −0.15 −0.85 266

a

Calculated rotational parameters at the MP2/6-311++G(d,p) level of theory. Rotational constants at the B2PLYP-D3BJ/aug-cc-pVTZ level of theory are also included after the slash (/). bCalculated relative energies (cm−1) at the B2PLYP-D3BJ/aug-cc-pVTZ level of theory, including harmonic zero-point energy correction.

unambiguous assignment of conformers A, B, C, and D to structures I [II3(g−g+)], III [II2(g+g−)], II [I2(g+g−)], and IV [I2(g−g−)], respectively. For propane-1,2,3-triamine, the asymmetry parameters of the calculated structures divide into three groups with values near κ = −0.34, −0.85, and −0.91 (Table 7). Unfortunately, due to limited sample size, only a small number of the most intense rotational transitions could be definitively assigned at the present signal level, making our assignments somewhat more tentative. Nevertheless, transitions due to two structures in each of the last two families are tentatively assigned. These are confirmed and strengthened by nuclear quadrupole splittings associated with these transitions. Detailed comparison of the values of the 14N quadrupole coupling constants lead to the identification of conformer A and C as structure I and IV in the κ = −0.85 family, whereas conformers B and D are assigned to structures II and VI in the κ = −0.91 family, respectively.

structure III over structure VI, the two unassigned conformers in the κ ≈ -0.85 category. On the basis of the CP-FTMW spectrum (Figure S1), transitions due to four conformers of 1,3-diamino-2-propanol have been assigned. A wider variety of κ value groups is observed in this case than in 2-amino-1,3-propanediol. Five groups are identified (κ = −0.29, −0.42, −0.73, −0.88, and −0.92) in the eight conformations with energies within 500 cm−1 of the global minimum. Among the higher-energy structures are two (structures V and VIII) that incorporate only a single hydrogen bond (κ = −0.29 and −0.73). More complex hyperfine splitting patterns are observed with the presence of the second nitrogen atom, leading to a new set of nuclear quadrupole coupling tensors χaa, χbb, χcc for each structure as summarized in Table 5. In this way, within each subgroup determined by different κ values, the predicted 14N quadrupole coupling constants are different enough to make an 60


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percent population. It is unlikely that collisional removal of the cyclic conformer population during the cooling process was occurring, because the calculated barrier between the cycle and the global minimum chain, II2(g+g+), is calculated to be around 1300 cm−1, large enough to trap population behind it during the cooling process. A small number of very weak transitions remain unassigned in each spectrum. They might come from other conformers that lie at higher energies or 13C isotopes of more stable structures. However, due to their weak intensities, no further assignments were possible.

Table 8. Experimental Rotational Parameters of the Four Assigned Conformers of Propane 1,2,3-triamine A (MHz) B (MHz) C (MHz) N1χaa (MHz) N1χbb (MHz) N1χcc (MHz) N3χaa (MHz) N3χbb (MHz) N3χcc (MHz) N5χaa (MHz) N5χbb (MHz) N5χcc (MHz) Nb κ μa:μb:μc

A

B

C

D

5769.44(4)a 2233.75(9) 1943.57(1) 3.56(1) −4.46(4) 0.90(4) −0.14(2) 2.17(4) −2.02(4) 0.15(2) −1.94(2) 1.78(2) 14 −0.85 c>a>b

7630.95(5) 1932.55(1) 1663.83(8) 3.61(6) −4.26(8) 1.64(8) 1.28(3) 3.49(1) −3.20(1) 3.64(6) −3.33(5) 1.31(5) 16 −0.91 b>c>a

5777.45(2) 2195.76(1) 1907.41(1) 1.65(1) −1.70(3) 0.04(3) −3.60(9) 2.02(7) 1.58(7) 2.10(1) 1.37(2) −4.53(2) 18 −0.85 a>b>c

7309.08(8) 1910.06(1) 1657.83(7) 2.42(6) −4.87(1) 1.459(1) −2.30(6) 1.27(2) 1.03(2) −1.46(6) 0.49(1) 0.97(1) 9 −0.91 a>b>c

IV. DISCUSSION One of the primary motivations for studying the microwave spectroscopy of the present series of amino alcohols and triamines is the opportunity they afford for probing in some detail the inherent conformational preferences of alkyl chains decorated with amino and alcohol functional groups. Building on previous results for glycerol, with 3 OH groups,11 prototypical propyl derivatives with two OH/one NH2, one OH/two NH2, and three NH2 groups were studied. Firm assignments were made for a total of 15 conformers of four molecules were made, and their relative populations determined. A. Comparing Predicted Energies and Observed Populations. Before considering the conformational preferences of the molecules in this series, it is important first to test the levels of theory that are best used in making comparison with experiment. The principal experimental results from the microwave spectra are the fitted rotational constants, dipole moment directions, and nuclear hyperfine splitting parameters used for conformational assignments. The experimental results (rotational constants, dipole moment components, and nuclear

a

Errors in parentheses are expressed in units of the last digit. bNumber of fitted lines, including nuclear hyperfine components.

Interestingly, structure II has a central double-donor NH2 group (H2N ← HNH → NH2), and is formally a IV2(g−g+) structure in our nomenclature, forming a bifurcated chain. The lone calculated κ = −0.34 structure (structure III) adopts a cyclic conformation with three connected NH···N intramolecular hydrogen bonds. The dipole moment of this structure is rather small but is directed almost exclusively along the out-of-plane c-axis. Given the signal-to-noise ratio on the spectrum (Figure S2), we anticipated being able to observe this conformer experimentally; however, no c-type transitions were observed near their predicted frequencies. The present signal levels leads to an upper bound of 20% (for S/N = 3) on its

Table 9. Percent Populations of the Observed Conformers and Comparison of Their Relative Energies Calculated at the B2PLYP-D3BJ/aug-cc-pVTZ Level of Theory molecule D-allothreoninol

2-amino-1,3-propanediol

1,3-diamino-2-propanol

propane-1,2,3-triamine

glycerold

conformer

population (%)a

population (%)b

ΔE(B2PLYP)c (cm−1)

II (A)/cycle/II3(g+g−) I(B)/curved chain/II2(g−g−) III (C)/cycle/I3(g+g−) II (A)/cycle/I3(g−g+) I (B)/curved chain/I2(g−g−) III (C)/curved chain/II2(g−g−) V(D)/extended chain/II2(g−g+) I(A)/cycle/II3(g−g+) III(B)/extended chain/II2(g+g−) II(C)/extended chain/I2(g+g−) IV(D)/curved chain/I2(g−g−) I(A)/curved chain/II2(g+g+) II(B)/extended chain/IV2(g−g+) IV(C)/curved chain/II2(g−g−) VI(D)/extended chain/II2(g−g+) 1a/cycle/II3(g−g+) 2b/curved chain/II2(g+g+) 3b/curved chain/II2(g+g+) 5c/extended chain/II2(g+g−) 7/curved chain/I2(g+g+)

58 37 5 52 37 8 3 34 31 21 14 59 22 17 2

48 44 8 56 33 6 5 40 29 22 9 58 20 18 4

0 58 188 55 0 204 201 0 95 112 239 0 64 221 188 0 57 205 235 394

large large small small small

a

Population percentage determined by summing the total intensities of a-, b-, and c-type transitions and dividing by the square of the theoretically predicted electronic dipole moments. bPopulation percentage determined by using the scale factors obtained from the best fit to the intensities for each conformer in rotational fitting program (JB95). cCalculated relative energies (cm−1) at the B2PLYP-D3BJ/aug-cc-pVTZ level of theory, including harmonic zero-point energy correction. dTaken from ref 11 (Ilyushin et al.). 61


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The Journal of Physical Chemistry A hyperfine splittings) are compared to the different calculations that were used. The comparison revealed a good agreement among the MP2and B2PLYP methods with the experiment, strengthening the conclusion10 that MP2/6-311++G(d,p) is a good level of theory for matching experimental rotational constants with theoretical predictions. Having made conformational assignments, the other major experimental findings of the present work are the percentage populations of the assigned conformations, extracted from the relative intensities of the microwave transitions. The percent populations of the observed conformers are summarized in Table 9 for the four molecules in this series. The table also includes a comparison of their calculated relative energies at the B2PLYP-D3BJ/aug-cc-pVTZ level of theory which has proven to be most consistent among the methods across the series compared to experiment. In the Supporting Information (Table S5−S8), further comparisons of the calculated relative energies at the MP2, B3LYP-D3BJ, and M05-2X levels with the aug-ccpVTZ basis set can be found. In the Discussion that follows, we use the B2PLYP-D3BJ calculations as the principal point of comparison with experiment. Although the precise energy differences vary from one method to the next, all the dispersion-corrected functionals perform well with this large basis set, and in general appear to be converging toward similar relative energies. In most cases, the percent populations correlate remarkably well with the calculated relative energies, given the small energy differences involved. To cite some examples, in D-allothreoninol, 1,3-diamino-2propanol, and propane-1,2,3-triamine, the measured percent populations in the supersonic expansion follow the calculated energy ordering and even the magnitudes of the energy differences in most cases (Table 9). In 2-amino-1,3-propanediol, the lowest energy cyclic [I3(g−g+)] and curved-chain [I2(g−g−)] structures carry most of the population, also as predicted by theory. Even in glycerol, where previous studies had not extracted relative populations quantitatively, the qualitative population sizes match the calculated energies quite well. At the same time, the correlation between experimental populations and conformer energies is not perfect. For instance, in 2-amino-1,3-propanediol, B2PLYP calculations predict that the curved chain conformer B [I2(g−g−)] is the global minimum, with the cyclic conformer A [I3(g−g+)] slightly higher in energy, by 55 cm −1 . However, the experimental percent population of A (56%) is almost twice that of B (33%), pointing to the cycle as the global minimum. More importantly, some structures predicted by calculation to have low energies are “missing” in the expansion. For instance, in D-allothreoninol, structure IV in Table 1 (II2(g− g−) configuration) was not observed experimentally although its energy is nearly isoenergetic with structure III [I3(g+g−)], assigned to conformer C, which carries 8% of the observed population. Structural relaxation29 into a lower-energy conformation through interconversion over a low-energy barrier is suggested. This process can occur in the early stages of supersonic expansion as a result of collisions with buffer gas. Figure 2a shows the interconversion barrier between structure IV and structure I listed in Table 1 for D-allothreoninol. Both these structures belong to the II2(g−g−) structural family and differ from each other by a rotation of the free OH group in the curved-chain structure, effectively switching which lone pair on the oxygen atom is used as H-bond acceptor site. Because a low-energy interconversion barrier of 275 cm−1 is predicted, the higher-energy conformer is able to relax into the lower-energy

Figure 2. (a) Interconversion barrier between structure IV to structure I of D-allothreoninol at the B3PLYP-D3BJ/aug-cc-pVTZ level of theory. (b) Interconversion barrier between structure IV to structure I for 2-amino-1,3-propanediol at the B3PLYP-D3BJ/aug-cc-pVTZ level of theory.

minimum during the collisional cooling in the expansion. This process will increase the population of structure I (conformer B) and decrease the population of structure IV, which is not found in the expansion. In 2-amino-1,3-propanediol, a similar low-barrier pathway exists between structure IV and structure I (322 cm−1 barrier, Figure 2b), or structure VIII and structure V (324 cm−1 barrier), explaining the inability to detect population in either structure IV or VIII experimentally. Finally, in propane-1,2,3triamine (Table 7), the cyclic structure III [II3(g−g+)] is not observed experimentally, despite being lower in energy than two others that are observed (structures II and IV). The fact that the cycle is not observed is due in part to its lower dipole moment, which points almost exclusively along the c-axis; however, given the small energy difference between structures III and I, a low-energy pathway may be implicated as well. Taken as a whole, these results provide further evidence that the relative populations of conformers observed in the expansion are determined not only by their relative stabilities but also to some extent by the sizes of the isomerization barriers between them.30 Where differences occur in the ordering of populations by energy, a low-energy isomerization pathway is likely responsible for the observed discrepancy, draining population from a higher-energy minimum into a lower-energy one during the collisional cooling process. Indeed, Ruoff et al.29 have deduced on the basis of small molecule cooling in expansions that collisional removal of a higherenergy conformer is possible when the barrier to isomerization is less than 400 cm−1, consistent with our deductions. 62


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Figure 3. Calculated energy level diagrams for glycerol, 2-amino-1,3-propanediol, 1,3-diamino-2-propanol, and propane-1,2,3-triamine through B2PLYP-D3BJ/aug-cc-pVTZ level of theory.

B. Preference for Cycles versus Chains as a Function of NH2/OH Content. The small amino alcohol molecules studied in this work all possess three adjacent H-bonding substituents as a combination of NH2 and OH groups along the carbon framework. As a result, one similarity in their energy landscapes is that both cyclic and chain HB patterns are present, and in close energetic proximity. The hydrogenbonded chains incorporate two H-bonds linking adjacent substituents (α → β → γ or γ → β → α) along the carbon backbone. The cycles have three hydrogen bonds, closing the cycle by forming a hydrogen bond between the α and γ carbons. Figure 3 shows a set of energy level diagrams for 2-amino1,3-propanediol (2 OH/1 NH2), 1,3-diamino-2-propanol (1 OH/2 NH2), and propane-1,2,3-triamine (3 NH2), calculated at the B2PLYP-D3BJ/aug-cc-pVTZ level of theory that best matches with experiment. As a point of comparison, the relative energies of different structures of glycerol are also calculated at the same level of theory and are included in the figure. In all four members of the series, the lowest energy cyclic and chain structures are within around 200 cm−1 of one another. 2Amino-1,3-propanediol has the smallest gap, with chain more stable than the cycle (ΔE = Ecycle − Echain = 55 cm−1), whereas the largest gap is found in propane-1,2,3-triamine, with chain preferred over cycle again (ΔE = 201 cm−1). The calculated structures for the full set of observed conformers in the series 2-amino-1,3-propanediol, 1,3-diamino-2-propanol, propane-1,2,3-triamine, and glycerol are shown in Figures 4−7, respectively. The structures are divided into the three major H-bond structural types: cycles, curved chains, and extended chains. The observed structures of 2-amino-1,3propanediol are prototypical (Figure 4), with one cycle, two curved chains, and one extended chain detected in the expansion. As Table 10 summarizes, the OCCC and CCCO dihedral angles (e.g., G, T) configure the terminal heavy atoms in positions where they can form cyclic, curved chain, or extended chain structures. These dihedrals are both gauche (but of opposite sign) in the cycle, the curved chain has one gauche and one trans, and the extended chain has two trans. To form H-bonds, adjacent OH/NH2 functional groups must be gauche with respect to one another, with XCCY dihedrals of approximately ±60°, as summarized in Table 10. The H-bonded cycles have XCCY dihedral angles that change sign along the carbon framework [(g+g−) or (g−g+)]. When combined with two gauche XCCC and CCCY dihedrals, the

Figure 4. Calculated structures for the full set of observed conformers of 2-amino-1,3-propanediol with calculated HB distances (in Å) at the B2PLYP-D3BJ/aug-cc-pVTZ level of theory. Assigned structural types and their relative energies calculated at the same level of theory are included. The global minimum is shaded in red, and the lowest energy local minimum is shaded in blue.

Figure 5. Calculated structures for the full set of observed conformers of 1,3-diamino-2-propanol with calculated HB distances (in Å) using B2PLYP-D3BJ/aug-cc-pVTZ level of theory. Assigned structural types and their relative energies calculated at the same level of theory are included. The global minimum is shaded in red, and the lowest energy local minimum is shaded in blue.

three OH/NH2 groups are positioned on the same side of the plane of the carbon framework, where three H-bonds can be formed. Interestingly, this combination of dihedrals built off the triangular carbon framework produces nearest-neighbor (α−β, 63


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XCCC/CCCY dihedrals in the trans configuration, minimizing steric strain in the carbon framework at both ends. XCCY dihedrals of opposite sign, (g−g+) or (g+g−), produces two Hbonds of medium strength. In propane-1,2,3-triamine, the lowest energy extended chain structure is a bifurcated chain, with the central NH2 group acting as a double donor to the two terminal amino groups. Table 11 compares the key structural parameters of the lowest energy chain and cyclic structures for each molecule in the series of glycerol, 2-amino-1,3-propanediol, 1,3-diamino-2propanol, and propane-1,2,3-triamine. These structures are highlighted in red (global minimum) and blue (second lowest) in Figures 4−7. Anticipating that a short, near-linear H-bond is best, we looked for a correlation between the XH···Y−H-bond distance and bond angle (180° = linear). Indeed, this correlation is evident in Figure 8, which plots the H-bond distance versus angle of the lowest-energy cyclic and chain structures of each molecule, grouped by H-bond type. The OH group is the better H-bond donor, forming all seven of the shortest H-bonds (r(OH···Y) < 2.25 Å), whereas eight of the ten longest have the poorer NH as H-bond donor (r(NH··· Y) > 2.30 Å). The anticipation that NH2 groups would be better acceptors than OH groups is not clearly borne out by the present data, in part because the range of H-bond distances of a given type is substantial. Thus, along an alkyl chain, nearestneighbor (α−β or β−γ) and next-nearest-neighbor (α−γ) Hbonds follow the order r(OH···N) ≈ r(OH···O)< r(NH···N)≈ r(NH···O). Although the cycle seems preferable over the chain by virtue of its extra H-bond, the triangular structure leads to H-bonds that are quite strained, and of unequal strength. As Figure 8 shows, the H-bonded chains (red symbols) are intermediate in length, pitting two medium-strength H-bonds against what is often a combination of strong and weak H-bonds in the cycle.10 Interestingly, at the B2PLYP-D3BJ/aug-cc-pVTZ level of theory, H-bonded cycles are preferred in glycerol and 1,3diamino-2-propanol, whereas a curved-chain structure is lowest in propane-1,2,3-triamine. In 2-amino-1,3-propanediol, the cycle and lowest-energy curved chain are close in energy, with calculation predicting the curved-chain lower, but experimental populations pointing toward the reverse. As the preceding discussion has amply illustrated, several counterbalancing factors contribute to the relative stability of cycle and chain in any one molecule, leaving no simple explanation of these trends. It is noteworthy, however, that the extended chains are quite high in energy in the molecules with two terminal OH groups (glycerol and 2-amino-1,3-propanediol) but drop in energy in the diamino and triamino analogs with one or more NH2 group on a terminal carbon. C. Effect of the Methyl Group on Structural Preferences. Figure 9 illustrates the effect of lengthening the carbon framework by addition of a methyl group at one end of 2-amino-1,3-propanediol. Depending on the chirality of the newly formed chiral center, either D-threoninol studied in previous work10 or D-allothreoninol studied here is formed. The preference for cycles over chains is retained in both molecules. This methyl group breaks the original symmetry of 2-amino1,3-propanediol, thus generating two unique conformers on the basis of each parent conformation of 2-amino-1,3-propanediol, as illustrated in Figure 9. The relative energies of the conformers in D-threoninol and D-allothreoninol are reasonably close to those in 2-amino-1,3propanediol, indicating that the addition of the methyl group

Figure 6. Calculated structures for the full set of observed conformers of propane-1,2,3-triamine with calculated HB distances (in Å) using B2PLYP-D3BJ/aug-cc-pVTZ level of theory. Assigned structural types and their relative energies calculated at the same level of theory are included. The global minimum is shaded in red, and the lowest energy local minimum, a bifurcated extended chain, is shaded in blue. Note that the cyclic structure was not observed experimentally (see text for further discussion).

Figure 7. Calculated structures for the full set of observed conformers of glycerol with calculated HB distances (in Å) using B2PLYP-D3BJ/ aug-cc-pVTZ level of theory. Assigned structural types from ref 11 and their relative energies calculated at the same level of theory are included. The global minimum is shaded in red, and the lowest energy local minimum is shaded in blue.

Table 10. Summary of the Sets of Dihedral Angles Associated with Each of the Prototypical H-Bonded Structural Types (X, Y = OH or NH2) dihedral angles structure type cycle curved chain extended chain

XC(α)C(β)Y

XC(β)C(γ)Y

XCCC

CCCX

g− g+ g− g+ g−

g+ g+ g− g− g+

G+ T G T T

G− G T T T

β−γ) and next-nearest-neighbor (γ−α) X···Y heavy-atom distances in the cyclic structures that are nearly equal (2.8 ± 0.1 Å, Table 11), so that an H-bond that closes the cycle could be similar in strength to a nearest-neighbor H-bond in a chain. The curved chains combine XCCY dihedrals of the same sign [(g+g+) or (g−g−)] with one gauche XCCC and one trans CCCY dihedral, thereby directing the H-bonded chain from above the plane of the carbon framework to in-plane, or vice versa. This trans configuration relieves strain along the carbon backbone relative to the cycle. The extended chains have both 64


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Table 11. Summary of Calculated XH···Y HB Distances (in Å) and Bond Angles (in deg) of the Lowest Energy Chain and Cyclic Structures for Each Molecule in the Series Glycerol, 2-Amino-1,3-propanediol, 1,3-Diamino-2-propanol, and Propane-1,2,3triamine at the B2PLYP-D3BJ/aug-cc-pVTZ Level of Theory cyclic OH···O

OH···N NH···O NH···N

glycerol

2-amino

2.11/134 2.19/117 2.62/97

2.10/136

2.30/109 2.40/106

chain diamino

triamino

glycerol

2-amino

diamino

2.23/115 2.33/107

2.17/117 2.53/102

triamino

2.33/108 2.21/112 2.03/123 2.63/96 2.36/118

2.29/113 2.30/123 2.54/99

2.48/104 2.38/109

does not change the energy landscape appreciably. More striking is the fact that there are significantly fewer conformers of D-allothreoninol detected in the expansion compared to Dthreoninol. This is in keeping with the energy level diagram calculated for this pair of disastereomers, as presented in Figure 10. As described in previous work,10 15 conformations of Dthreoninol were predicted by calculation to reside within 500 cm−1 of the global minimum at the MP2/6-311++G(d,p) level of theory, whereas only six conformations were found for its allo form in the same range. As a result, the seven lowest energy conformers (2 cycles and 5 chains) are assigned for Dthreoninol in the densely populated energy level diagram whereas only three (2 cycles and 1 chain) are found for Dallothreoninol. Calculations at the B2PLYP-D3J aug-cc-pVTZ confirm this conclusion (Figure 10). The lowest cyclic and chain structures of D-threoninol and Dallothreoninol are shown in the figure, together with Newman projections along the Cβ−Cγ bond. When viewed along the Cβ−Cγ chemical bond, the CH2OH group attached to the Cβ

Figure 8. Calculated H-bond distance (Å) versus XH···Y bond angles (degrees), at the B2PLYP-D3BJ/aug-cc-pVTZ level of theory, grouped by H-bond types.

Figure 9. Structural evolution from 2-amino-1,3-propanediol (center) to D-threoninol (left) and D-allothreoninol (right). Zero-point corrected relative energies (in cm−1) calculated at the B2PLYP-D3/aug-cc-pVTZ level of theory are included. Mirror image pairs in 2-amino-1,3-propanediol are included in the boxes. 65



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AUTHOR INFORMATION

Corresponding Author

*T. S. Zwier. E-mail: [email protected]. Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS Support for this work by the National Science Foundation is gratefully acknowledged [NSF CHE-1213289 and CHE1465028 ].

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Figure 10. Energy level diagrams for all conformational minima of Dthreoninol and D-allothreoninol within 500 cm−1 of the global minimum, calculated at the B2PLYP-D3/aug-cc-pVTZ level of theory. Conformers that are assigned in the expansion are shown in red. Structures of the lowest energy chain and cyclic conformers are also plotted with their Newman projections.

atom is in an anti configuration relative to the CH3 group on the back carbon in D-threoninol for both cyclic and chain structures. However, in D-allothreoninol, with its opposite chirality on the Cγ atom, a gauche conformation is adopted in both cases. We infer that D-allothreoninol experiences a larger steric hindrance brought on by the different chiral center, which raises the energy of the structures, and leads to a more sparsely populated energy level diagram, with fewer conformers with measurable population, as observed.

V. CONCLUSIONS The conformational preferences of a prototypical set of trisubstituted aminoalcohols (2-amino-1,3-propanediol, 1,3diamino-2-propanol, and D-allothreoninol), and the triamine analog 1,2,3-triaminopropane have been explored using a combination of broadband microwave spectroscopy and theoretical calculations. Rotational constants, dipole moment directions, and nuclear quadrupolar splittings are used to make firm assignments of a total of 15 conformations of the four molecules. By placing NH2 and OH functional groups on adjacent carbons along a propyl chain, one can form hydrogenbonded networks. The low-energy structures show a remarkable variety of H-bonding architectures, including cycles, curved chains, extended chains, and bifurcated chains. These architectures are in close energetic proximity, with subtle differences between molecules depending on the NH2/OH makeup and steric effects. Extending the sequence of NH2/OH groups to four or more promises an even richer variety of possibilities worth exploring.

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REFERENCES

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jpca.5b10650. Structures, energy differences, and rotational constants for all conformational minima (within 500 cm−1 of the global minimum) of D-allothreoninol, 2-amino-1,3propanol, 1,3-diamino-2-propanol, and propane-1,2,3triamine; Figures S1 and Figure S2 of experimental rotational spectra (PDF) 66


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Broadband Microwave Spectroscopy of Prototypical Amino Alcohols

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