N,N′-Bis[tris­(hy­droxy­meth­yl)meth­yl]propane-1,3-di­amine (bis-tris propane)

Angel-Nieto, I.; Arroyo-Carmona, R.E.; Pérez-Benítez, A.; Bernès, S.

doi:10.1107/S241431462500954X

organic compounds

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Volume 10| Part 11| November 2025| x250954

https://doi.org/10.1107/S241431462500954X

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N,N′-Bis[tris(hydroxymethyl)methyl]propane-1,3-diamine (bis-tris propane)

Ismael Angel-Nieto,^a Rosa Elena Arroyo-Carmona,^b Aarón Pérez-Benítez ^b and Sylvain Bernès ^a ^*

^aInstituto de Física Luis Rivera Terrazas, Benemérita Universidad Autónoma de Puebla, Av. San Claudio y 18 Sur, 72570 Puebla, Pue., Mexico, and ^bFacultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, 72570 Puebla, Pue., Mexico
^*Correspondence e-mail: [email protected]

Edited by M. Bolte, Goethe-Universität Frankfurt, Germany (Received 24 October 2025; accepted 29 October 2025; online 6 November 2025)

The title compound, C₁₁H₂₆N₂O₆, used for the preparation of buffer solutions and high-nuclearity coordination complexes, crystallizes with a half molecule in the asymmetric unit. The full molecule is completed through mirror symmetry m in the space group Pnma. The molecular shape is bent and, as a consequence, some H atoms are disordered to avoid too short H⋯H intramolecular contacts. Molecules in the crystal are linked via O—H⋯N and N—H⋯O hydrogen bonds, forming chains along [100], which are further packed through other O—H⋯O hydrogen bonds between hydroxy groups. The here-reported structure probably represents the less-stable form in a set of polymorphs.

Keywords: crystal structure; supramolecular structure; hydrogen bonds; polymorphism propensity.

CCDC reference: 2498903

Structure description

1,3-Bis[tris(hydroxymethyl)methylamino]propane, also known as bis-tris propane or BTP, is a diaminopolyol used in biochemistry and molecular biology for the preparation of buffer solutions in the wide pH range 6.0–9.5. It is readily soluble in water, and can be recrystallized as large plate-shaped single crystals (Fig. 1, inset).

Figure 1
Molecular structure of the title compound, with displacement ellipsoids for non-H atoms at the 30% probability level. H atoms with dashed bonds are disordered counterparts for crystallographically equivalent H atoms generated through m symmetry (x, $[{3\over 2}]$ − y, z). Non-labelled C, N and O atoms are generated using the same mirror symmetry. The top-left inset shows the single crystal used for data collection. It is ca. 0.7 mm long.

This polydentate molecule can also be used as a ligand for coordination chemistry. Crystal structures based on Cu²⁺ (e.g. Milway et al., 2013 ; Kirillova et al., 2017 ), V⁴⁺ (Nachtigall et al., 2017 ), polyoxidomolybdates (Li et al., 2015 ) and lanthanides (e.g. Yinling et al., 2022 ) have been reported. It is surprising that the crystal structure of the free ligand BTP has never been published.

BTP crystallizes in a centrosymmetric space group, Pnma, with the molecule placed on the mirror plane normal to the unit-cell b axis (Fig. 1). Within this structure, the molecule thus belongs to the C_s point group, although it does not display a trans-extended geometry, as might be expected. Instead, it adopts a bent-shaped geometry, defined by the gauche torsion angle N1—C2—C1—C2ⁱ = −70.4 (3)° [symmetry code: (i) x, $[{3\over 2}]$ − y, z]. This shape was previously observed for a Ca²⁺ complex (Liu et al., 2021 ) or in Cu²⁺ coordination compounds (Milway et al., 2013). The amine H atom is clearly disordered over two equally occupied positions, H1C and H1D, avoiding a short H⋯H contact [H1C⋯H1Cⁱ ≃ 1.4 Å], which would be destabilizing for the molecular structure. In the same way, the H atom for the hydroxy group O4 is disordered over two sites, H4C and H4D. An alternative would be to refine a non-disordered model in space group Pn2₁a, with independent amine H atoms fully occupying sites H1C and H1D on two independent N atoms, as well as hydroxy H atoms with full occupancy on two independent O4 atoms. Such a model refines well (R₁ = 0.039) but is unlikely, for two reasons: (i) convergence is not reached if H atoms are refined with free coordinates, and (ii) intensity statistics show a centric distribution, with, for example, <|Z − 1|> = 0.957 (theoretical: 0.968). These disordered H atoms also allow the formation of two intramolecular N—H⋯N and O—H⋯O hydrogen bonds, consolidating the bent conformation (Table 1, entries 1 and 2).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1C⋯N1ⁱ	0.86 (2)	2.24 (3)	2.970 (3)	143 (3)
O4—H4D⋯O4ⁱ	0.80 (3)	1.90 (3)	2.679 (3)	162 (6)
O4—H4C⋯N1ⁱⁱ	0.82 (3)	2.09 (3)	2.905 (2)	175 (4)
N1—H1D⋯O4ⁱⁱⁱ	0.82 (2)	2.09 (3)	2.905 (2)	169 (3)
O6—H6⋯O5ⁱⁱ	0.81 (2)	2.02 (3)	2.7390 (19)	148 (3)
O5—H5⋯O6^iv	0.85 (2)	1.88 (2)	2.7305 (18)	176 (3)
Symmetry codes: (i) $[x, -y+{\script{3\over 2}}, z]$ ; (ii) $[x+{\script{1\over 2}}, y, -z+{\script{1\over 2}}]$ ; (iii) $[x-{\script{1\over 2}}, y, -z+{\script{1\over 2}}]$ ; (iv) $[-x+{\script{1\over 2}}, -y+1, z+{\script{1\over 2}}]$ .

The crystal structure is essentially monoperiodic: the molecules form chains along the [100] direction through the intermolecular hydrogen bonds O4—H4C⋯N1ⁱⁱ and N1—H1D⋯O4ⁱⁱⁱ involving amine and hydroxy functional groups with disordered H atoms (Table 1, entries 3 and 4). Interchain O—H⋯O contacts build a network of fused centrosymmetric R₄⁴(8) and R₄⁴(24) ring motifs, parallel to the monoperiodic chains (see two last entries in Table 1 and Fig. 2).

Figure 2
Part of the crystal structure, as viewed down unit-cell axis c, showing the framework of hydrogen bonds (orange dashed lines). For the sake of clarity, only one position for disordered H atoms bonded to amine N1 and hydroxy O4 groups is retained, and all C-bonded H atoms are omitted.

The unexpected conformation reported herein for BTP could be a consequence of a propensity to polymorphism. The assessment of hydrogen-bond coordination likelihood of BTP was carried out using the hydrogen bond propensity tool available in Mercury (Galek et al., 2014 ; Macrae et al., 2020 ), with the CSD-6.00 database as a training dataset. The model refined in the Pn2₁a space group was used as a target, since the molecule is disorder-free, and the asymmetric unit includes the complete BTP molecule (Z′ = 1). The resulting hydrogen-bonding landscape is compelling (Fig. 3): in the map (mean hydrogen-bond pairing propensity, mean hydrogen-bond coordination), the here-reported crystal structure is found at coordinates (0.396, 0.709), while a more stable polymorph is predicted at coordinates (0.447, 0.819). We thus assume that the Ostwald's rule for the formation of polymorphs holds, and that we crystallized the less-stable form of BTP.

Figure 3
Hydrogen-bonding landscape for BTP, calculated with Mercury (Macrae et al., 2020

). The blue dot on the left-bottom corner corresponds to the here-reported structure, while the orange spot on the upper-right corner is for an hypothetical polymorph. N represents the number of intermolecular hydrogen-bond pairs, which are shown with different colours. For the regression analysis, the area under ROC curve was 0.835. Putative hydrogen-bonding networks were built with likelihood > 0.1, for both hydrogen-bond propensity and hydrogen-bond coordination.

Synthesis and crystallization

BTP, coming from a commercial supplier (Sigma-Aldrich), was recrystallized from a saturated water solution, at room temperature. Single crystals were obtained after a few days.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. All H atoms were visible in difference maps, and were refined with free coordinates and isotropic displacement parameters. O—H and N—H bond lengths were restrained to 0.85 (2) and 0.90 (2) Å, respectively. H atoms bonded to N1 and O4 are disordered over two positions (H1C/H1D and H4C/H4D), and their occupancies were fixed to 1/2.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₁H₂₆N₂O₆
M_r	282.34
Crystal system, space group	Orthorhombic, Pnma
Temperature (K)	296
a, b, c (Å)	10.7262 (3), 20.5189 (5), 6.4624 (3)
V (Å³)	1422.31 (8)
Z	4
Radiation type	Ag Kα, λ = 0.56083 Å
μ (mm⁻¹)	0.07
Crystal size (mm)	0.68 × 0.15 × 0.05

Data collection
Diffractometer	Stoe Stadivari
Absorption correction	Multi-scan (LANA; Stoe, 2025 )
T_min, T_max	0.960, 0.997
No. of measured, independent and observed [I > 2σ(I)] reflections	68162, 1942, 1392
R_int	0.058
(sin θ/λ)_max (Å⁻¹)	0.682

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.047, 0.140, 1.08
No. of reflections	1942
No. of parameters	150
No. of restraints	6
H-atom treatment	All H-atom parameters refined
Δρ_max, Δρ_min (e Å⁻³)	0.25, −0.22
Computer programs: X-AREA Pilatus3-SV, X-AREA Recipe, X-AREA Integrate and LANA (Stoe, 2025), SHELXT2018/2 (Sheldrick, 2015a ), SHELXL2025/1 (Sheldrick, 2015b ), XP in SHELXTL-Plus (Sheldrick, 2008 ), Mercury (Macrae et al., 2020) and publCIF (Westrip, 2010 ).

Structural data

CCDC reference: 2498903

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S241431462500954X/bt4185sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S241431462500954X/bt4185Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S241431462500954X/bt4185Isup3.cml

checkCIF report

Computing details top

N,N'-Bis[tris(hydroxymethyl)methyl]propane-1,3-diamine top

Crystal data top

C₁₁H₂₆N₂O₆	D_x = 1.319 Mg m⁻³
M_r = 282.34	Melting point: 437 K
Orthorhombic, Pnma	Ag Kα radiation, λ = 0.56083 Å
a = 10.7262 (3) Å	Cell parameters from 34115 reflections
b = 20.5189 (5) Å	θ = 2.9–26.7°
c = 6.4624 (3) Å	µ = 0.07 mm⁻¹
V = 1422.31 (8) Å³	T = 296 K
Z = 4	Plate, colourless
F(000) = 616	0.68 × 0.15 × 0.05 mm

Data collection top

Stoe Stadivari diffractometer	1942 independent reflections
Radiation source: Sealed X-ray tube, Axo Astix-f Microfocus source	1392 reflections with I > 2σ(I)
Graded multilayer mirror monochromator	R_int = 0.058
Detector resolution: 5.81 pixels mm^-1	θ_max = 22.5°, θ_min = 3.0°
ω scans	h = −14→12
Absorption correction: multi-scan (LANA; Stoe, 2025)	k = −28→28
T_min = 0.960, T_max = 0.997	l = −8→8
68162 measured reflections

Refinement top

Refinement on F²	Primary atom site location: dual
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.047	Hydrogen site location: difference Fourier map
wR(F²) = 0.140	All H-atom parameters refined
S = 1.08	w = 1/[σ²(F_o²) + (0.0665P)² + 0.2802P] where P = (F_o² + 2F_c²)/3
1942 reflections	(Δ/σ)_max < 0.001
150 parameters	Δρ_max = 0.25 e Å⁻³
6 restraints	Δρ_min = −0.22 e Å⁻³

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq	Occ. (<1)
C1	0.1413 (2)	0.750000	0.6466 (4)	0.0518 (6)
H1A	0.064 (3)	0.750000	0.554 (5)	0.053 (7)*
H1B	0.104 (3)	0.750000	0.788 (5)	0.071 (9)*
C2	0.2155 (2)	0.68773 (9)	0.6187 (3)	0.0546 (5)
H2A	0.291 (2)	0.6900 (11)	0.706 (4)	0.080 (7)*
H2B	0.168 (2)	0.6504 (12)	0.675 (4)	0.075 (6)*
N1	0.25043 (14)	0.67764 (6)	0.4019 (2)	0.0429 (3)
H1C	0.275 (3)	0.7150 (13)	0.357 (5)	0.043 (9)*	0.5
H1D	0.188 (3)	0.6744 (16)	0.329 (5)	0.033 (8)*	0.5
C3	0.33326 (13)	0.62212 (7)	0.3552 (2)	0.0398 (3)
C4	0.46486 (15)	0.63221 (9)	0.4434 (3)	0.0510 (4)
H4A	0.5140 (18)	0.5938 (10)	0.417 (3)	0.050 (5)*
H4B	0.4579 (17)	0.6395 (9)	0.596 (3)	0.050 (5)*
O4	0.52710 (14)	0.68472 (8)	0.3514 (3)	0.0724 (5)
H4C	0.592 (3)	0.6809 (18)	0.284 (6)	0.048 (10)*	0.5
H4D	0.519 (6)	0.7230 (15)	0.375 (9)	0.12 (3)*	0.5
C5	0.28593 (15)	0.55783 (8)	0.4441 (3)	0.0501 (4)
H5A	0.343 (2)	0.5226 (10)	0.405 (3)	0.059 (5)*
H5B	0.293 (2)	0.5591 (10)	0.591 (4)	0.062 (6)*
O5	0.16180 (11)	0.54508 (7)	0.3811 (2)	0.0631 (4)
H5	0.136 (3)	0.5082 (12)	0.423 (5)	0.103 (9)*
C6	0.33686 (17)	0.62006 (8)	0.1183 (3)	0.0479 (4)
H6A	0.2525 (18)	0.6105 (9)	0.072 (3)	0.051 (5)*
H6B	0.3643 (18)	0.6628 (10)	0.065 (3)	0.058 (5)*
O6	0.41686 (13)	0.57189 (6)	0.0346 (2)	0.0616 (4)
H6	0.490 (2)	0.5798 (15)	0.052 (5)	0.104 (10)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0506 (12)	0.0636 (15)	0.0410 (12)	0.000	0.0170 (11)	0.000
C2	0.0696 (11)	0.0542 (10)	0.0400 (9)	0.0025 (9)	0.0154 (8)	0.0084 (7)
N1	0.0535 (8)	0.0364 (6)	0.0388 (7)	0.0008 (6)	0.0116 (6)	0.0046 (5)
C3	0.0404 (7)	0.0332 (7)	0.0458 (8)	−0.0037 (6)	0.0032 (6)	0.0031 (6)
C4	0.0406 (8)	0.0500 (9)	0.0625 (11)	−0.0065 (7)	0.0037 (8)	−0.0049 (8)
O4	0.0602 (8)	0.0573 (8)	0.0998 (12)	−0.0234 (7)	0.0339 (8)	−0.0183 (8)
C5	0.0407 (7)	0.0407 (8)	0.0690 (12)	−0.0048 (6)	−0.0056 (8)	0.0159 (8)
O5	0.0443 (6)	0.0509 (7)	0.0941 (11)	−0.0121 (5)	−0.0080 (6)	0.0221 (7)
C6	0.0555 (9)	0.0386 (8)	0.0496 (9)	0.0020 (7)	0.0062 (8)	−0.0051 (7)
O6	0.0526 (7)	0.0546 (7)	0.0776 (9)	0.0017 (6)	0.0052 (7)	−0.0260 (7)

Geometric parameters (Å, º) top

C1—C2ⁱ	1.515 (2)	C4—O4	1.400 (2)
C1—C2	1.515 (2)	C4—H4A	0.96 (2)
C1—H1A	1.02 (3)	C4—H4B	1.00 (2)
C1—H1B	1.00 (3)	O4—H4C	0.82 (3)
C2—N1	1.465 (2)	O4—H4D	0.80 (3)
C2—H2A	0.99 (3)	C5—O5	1.417 (2)
C2—H2B	0.99 (3)	C5—H5A	0.98 (2)
N1—C3	1.4759 (19)	C5—H5B	0.95 (2)
N1—H1C	0.86 (2)	O5—H5	0.85 (2)
N1—H1D	0.82 (2)	C6—O6	1.416 (2)
C3—C5	1.526 (2)	C6—H6A	0.973 (19)
C3—C6	1.532 (2)	C6—H6B	0.99 (2)
C3—C4	1.536 (2)	O6—H6	0.81 (2)

C2ⁱ—C1—C2	114.9 (2)	O4—C4—C3	112.62 (16)
C2ⁱ—C1—H1A	111.0 (7)	O4—C4—H4A	107.1 (11)
C2—C1—H1A	111.0 (7)	C3—C4—H4A	109.2 (11)
C2ⁱ—C1—H1B	108.6 (8)	O4—C4—H4B	109.7 (11)
C2—C1—H1B	108.6 (8)	C3—C4—H4B	108.5 (11)
H1A—C1—H1B	102 (2)	H4A—C4—H4B	109.6 (16)
N1—C2—C1	111.53 (16)	C4—O4—H4C	124 (3)
N1—C2—H2A	109.8 (15)	C4—O4—H4D	128 (5)
C1—C2—H2A	108.9 (14)	H4C—O4—H4D	106 (5)
N1—C2—H2B	111.9 (14)	O5—C5—C3	111.35 (14)
C1—C2—H2B	109.7 (13)	O5—C5—H5A	111.9 (12)
H2A—C2—H2B	104.7 (19)	C3—C5—H5A	109.6 (12)
C2—N1—C3	117.32 (14)	O5—C5—H5B	111.2 (14)
C2—N1—H1C	106 (2)	C3—C5—H5B	109.1 (13)
C3—N1—H1C	116 (2)	H5A—C5—H5B	103.4 (18)
C2—N1—H1D	110 (2)	C5—O5—H5	112 (2)
C3—N1—H1D	108 (2)	O6—C6—C3	114.61 (15)
H1C—N1—H1D	98 (3)	O6—C6—H6A	107.8 (11)
N1—C3—C5	112.95 (13)	C3—C6—H6A	106.8 (11)
N1—C3—C6	103.95 (12)	O6—C6—H6B	107.8 (12)
C5—C3—C6	111.15 (14)	C3—C6—H6B	109.4 (12)
N1—C3—C4	111.92 (13)	H6A—C6—H6B	110.4 (16)
C5—C3—C4	106.41 (13)	C6—O6—H6	113 (2)
C6—C3—C4	110.56 (14)

C2ⁱ—C1—C2—N1	−70.4 (3)	C6—C3—C4—O4	50.48 (19)
C1—C2—N1—C3	174.27 (15)	N1—C3—C5—O5	53.8 (2)
C2—N1—C3—C5	52.1 (2)	C6—C3—C5—O5	−62.6 (2)
C2—N1—C3—C6	172.74 (15)	C4—C3—C5—O5	176.99 (16)
C2—N1—C3—C4	−67.92 (19)	N1—C3—C6—O6	176.97 (13)
N1—C3—C4—O4	−64.88 (19)	C5—C3—C6—O6	−61.23 (19)
C5—C3—C4—O4	171.30 (16)	C4—C3—C6—O6	56.72 (18)

Symmetry code: (i) x, −y+3/2, z.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1C···N1ⁱ	0.86 (2)	2.24 (3)	2.970 (3)	143 (3)
O4—H4D···O4ⁱ	0.80 (3)	1.90 (3)	2.679 (3)	162 (6)
O4—H4C···N1ⁱⁱ	0.82 (3)	2.09 (3)	2.905 (2)	175 (4)
N1—H1D···O4ⁱⁱⁱ	0.82 (2)	2.09 (3)	2.905 (2)	169 (3)
O6—H6···O5ⁱⁱ	0.81 (2)	2.02 (3)	2.7390 (19)	148 (3)
O5—H5···O6^iv	0.85 (2)	1.88 (2)	2.7305 (18)	176 (3)

Symmetry codes: (i) x, −y+3/2, z; (ii) x+1/2, y, −z+1/2; (iii) x−1/2, y, −z+1/2; (iv) −x+1/2, −y+1, z+1/2.

Funding information

Funding for this research was provided by: Consejo Nacional de Ciencia y Tecnología (grant No. 268178; scholarship No. 928228 to Ismael Angel-Nieto). APB thanks VIEP-BUAP for the financial support to Project 00075-PVG/2025.

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