organic compounds
`
`only two similar structures, namely oxonium phyllo-hexakis-
`[dihydrogenphosphate(V)]
`bis[hydrogenphosphate(V)]tri-
`aluminate tetrahydrate, (H3O)[Al3(H2PO4)6(HPO4)2](H2O)4
`(Brodalla & Kniep, 1980; R = 0.051), and aluminium phyllo-
`dihydrogenphosphate hydrogenphosphate hydrate, Al(H2-
`PO4)(HPO4)(H2O) (Kniep et al., 1978; R = 0.033). In both
`compounds, the O atoms of the anions are simultaneously
`coordinated to the Al atoms.
`Among the compounds listed in the Cambridge Structural
`Database (CSD, Version 5.26; Allen, 2002) there are only
`three structures with the title anions and with R factors (cid:20) 0.05,
`namely
`tris(hordenine) monohydrogenphosphate
`di-
`hydrogenphosphate monohydrate
`(refcode KAWMOK;
`Mukhopadhyay et al., 1989), hexakis(melaminium) tetrakis-
`(dihydrogenphosphate) monohydrogenphosphate
`tetrahy-
`drate (refcode XORYAE; Janczak & Perpe´ tuo, 2002) and tris-
`(2-ammonioethyl)amine dihydrogenphosphate monohydro-
`
`Figure 1
`A view of the constituent ions in (I), with anisotropic displacement
`parameters drawn at the 50% probability level.
`
`Acta Crystallographica Section C
`Crystal Structure
`Communications
`
`ISSN 0108-2701
`
`Tris(methylammonium) hydrogen-
`phosphate dihydrogenphosphate
`
`Jan Fa´bry,* Radmila Krupkova´, Prˇemysl Vaneˇk and Michal
`Dusˇek
`
`Institute of Physics, Czech Academy of Sciences, Na Slovance 2, 182 21 Praha 8,
`Czech Republic
`Correspondence e-mail: fabry@fzu.cz
`
`Received 13 September 2005
`Accepted 14 December 2005
`Online 14 January 2006
`
`The title compound, 3CH6N+(cid:1)HPO42(cid:255)(cid:1)H2PO4
`
`(cid:255), aggregates
`with the moieties interconnected by O—H(cid:1)(cid:1)(cid:1)O and N—
`H(cid:1)(cid:1)(cid:1)O hydrogen bonds, with O(cid:1)(cid:1)(cid:1)O and N(cid:1)(cid:1)(cid:1)O distances
`in the ranges 2.5366 (16)–2.5785 (14) and 2.7437 (16)–
`2.9967 (18) A˚ , respectively. Three C—H(cid:1)(cid:1)(cid:1)O hydrogen bonds
`are also present, with C(cid:1)(cid:1)(cid:1)O distances
`in the range
`3.2310 (18)–3.3345 (17) A˚ . All H atoms are ordered. Struc-
`tures with ordered hydrogenphosphate and dihydrogen-
`phosphate components are rare.
`
`Comment
`
`Interest in the present study was influenced by properties
`observed
`in
`n-alkylammonium dihydrogenphosphates,
`+(cid:1)H2PO4CnH2n+1NH3
`(cid:255). In these compounds, ferroelastic phase
`
`transitions arise, as discovered by Kroupa & Fuith (1993,
`1994). Phase transitions and ferroelastic switching are related
`to the hydrogen-bond patterns in these derivatives (see, for
`example, Kasatani et al., 1998; Fa´ bry et al., 2000), and so a goal
`in this field is to prepare compounds in this class and deter-
`mine their crystal structures. However,
`the structure of
`methylammonium dihydrogenphosphate, (II), the simplest
`compound in the series, has not been reported to date. Crys-
`tals of the title compound, (I), grew accidentally during our
`attempts to grow crystals of (II). We present here the crystal
`structure of (I).
`
`The most interesting feature of (I) is the cocrystallization of
`the dihydrogenphosphate and hydrogenphosphate anions in
`an ordered arrangement. Although this is not unprecedented,
`the simultaneous occurrence of both anions in an ordered way
`is quite rare. Among inorganic structures present in the
`Inorganic Crystal Structure Database (ICSD, 2004) there are
`
`Figure 2
`A view of the unit cell of (I) along the b axis. Methyl H atoms have been
`omitted.
`
`Acta Cryst. (2006). C62, o73–o75
`
`DOI: 10.1107/S0108270105041934
`
`# 2006 International Union of Crystallography o73
`
`Merck Exhibit 2216, Page 1
`Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp.
`IPR2020-00040
`
`

`

`organic compounds
`
`genphosphate (refcode WAKBAM; Dakhlaoui et al., 2004).
`The P—O bond lengths of these structure determinations
`correlate well with those in (I).
`The moieties in (I) are interconnected by hydrogen bonds
`and there are several
`important points
`regarding the
`hydrogen-bond pattern. Firstly, the hydrogen-bond donor
`atoms O14, O23 and O24 do not act as hydrogen-bond
`acceptors, except for atom O14, which is involved in a weak
`C—H(cid:1)(cid:1)(cid:1)O hydrogen bond (Table 2). Secondly, there is a
`difference between the [HPO4]2(cid:255) and [H2PO4](cid:255) anions in the
`number of H atoms accepted from the ammonium groups. The
`O atoms belonging to the [HPO4]2(cid:255) anion accept seven H
`atoms from the ammonium groups,
`in contrast with the
`[H2PO4](cid:255) anion, which accepts only two H atoms of this kind.
`In addition, the O atoms of the [HPO4]2(cid:255) anion accept two
`other hydroxyl H atoms, so each of these acceptor O atoms of
`the latter anion is fully saturated by three H atoms. The fact
`that the [HPO4]2(cid:255) anion accepts more H atoms than [H2PO4](cid:255)
`can be related to the higher formal negative charge of the
`former, to the values of the first and second degree dissocia-
`II (1.3 and 6.70, respectively; Lide,tion constants pKaI and pKa
`
`
`1997), and to the obvious fact that a hydroxyl group can accept
`fewer H atoms than an oxo group. Thirdly, O—H(cid:1)(cid:1)(cid:1)O
`hydrogen bonds interconnect the [HPO4]2(cid:255) and [H2PO4](cid:255)
`anions into columns passing through the structure along the b
`axis. The methylammonium groups that interconnect all the
`molecules into a three-dimensional network are attached to
`these molecules. Fourthly, the higher displacement parameters
`of atom N3 in one of the methylammonium groups can be
`attributed to a weaker hydrogen bond in comparison with
`atoms N1 and N2 (cf. Table 1). Consequently, the same holds
`for atom C3 in comparison with atoms C1 and C2. The P—
`O(cid:1)(cid:1)(cid:1)A angles, where A is an acceptor N or O atom, are in the
`three C—H(cid:1)(cid:1)(cid:1)O
`108.00 (6)–128.00 (6)(cid:14). Finally,
`range
`hydrogen bonds (Table 2) complete the hydrogen bonding and
`conform to the criteria given by Desiraju & Steiner (1999).
`
`Experimental
`
`Crystals of (I) were grown from a mixture of methylamine and
`phosphoric acid in a stoichiometric ratio of 1:1 in an attempt to
`prepare methylammonium dihydrogenphosphate, (II). An ethanol–
`water solution (30:70 vol%) of the mixture was placed in a refrig-
`erator at (cid:24)280 K and left there for several months. During this
`period, part of
`the sample became dry and possibly partially
`decomposed, as could be judged from a yellowish taint. From this
`light-yellow bulk grew several centimetre-long colourless needle-like
`crystals of (I), with cross-sections measuring several millimetres. The
`beaker also contained the desired crystals of (II), of a size of several
`tenths of a millimetre. The quality of the crystals of (II) was inferior
`to the demands of single-crystal diffractometry. The crystals of (I) are
`clearly less hygroscopic than those of (II). Calorimetric experiments
`were performed on Perkin–Elmer DSC 7 and Pyris Diamond
`differential scanning calorimeters using PYRIS software (Perkin–
`Elmer, 2001), with m = 5 mg, a temperature interval of 93–398 K and
`a scanning rate of 10 K min(cid:255)1. No structural phase transitions were
`detected, either on heating or on cooling. The symptoms of decom-
`position commenced at 378 K.
`
`o74 Jan Fa´bry et al.
`
`
`
`(cid:15) 3CH6N+(cid:1)HPO42(cid:255)(cid:1)H2PO4
`
`(cid:255)
`
`(cid:255)
`
`2(cid:255)(cid:1)H2PO4
`
`Crystal data
`3CH6N+(cid:1)HPO4
`Mr = 289.2
`Monoclinic, P21=n
`a = 12.3571 (6) A˚
`b = 6.5465 (2) A˚
`c = 15.1231 (6) A˚
`(cid:12) = 95.556 (4)(cid:14)
`V = 1217.65 (9) A˚ 3
`Z = 4
`
`Data collection
`
`Oxford Diffraction Xcalibur CCD
`area-detector diffractometer
`Rotation method data acquisition
`using ! scans
`Absorption correction: analytical
`[Crysalis RED (Oxford
`Diffraction, 2005); method by
`Clark & Reid (1995)]
`Tmin = 0.877, Tmax = 0.937
`
`Refinement
`
`Refinement on F 2
`R(F ) = 0.026
`wR(F 2) = 0.080
`S = 1.89
`2498 reflections
`154 parameters
`
`Table 1
`Selected bond lengths (A˚ ).
`
`Dx = 1.577 Mg m(cid:255)3
`Mo K(cid:11) radiation
`Cell parameters from 20259
`reflections
`(cid:18) = 3.3–26.4(cid:14)
`(cid:22) = 0.39 mm(cid:255)1
`T = 120 K
`Prism, colourless
`0.41 (cid:2) 0.27 (cid:2) 0.11 mm
`
`20259 measured reflections
`2498 independent reflections
`2187 reflections with I > 3(cid:27)(I)
`Rint = 0.026
`(cid:18)max = 26.4(cid:14)
`h = (cid:255)15 ! 15
`k = (cid:255)8 ! 8
`l = (cid:255)18 ! 18
`
`H atoms treated by a mixture of
`independent and constrained
`refinement
`w = 1/[(cid:27)2(I) + 0.0009I2]
`((cid:1)/(cid:27))max = 0.001
`(cid:1)(cid:26)max = 0.29 e A˚ (cid:255)3
`(cid:1)(cid:26)min = (cid:255)0.39 e A˚ (cid:255)3
`
`P1—O11
`P1—O12
`P1—O13
`P1—O14
`P2—O21
`P2—O22
`
`1.5274 (11)
`1.5412 (11)
`1.5369 (11)
`1.5758 (11)
`1.5008 (12)
`1.5130 (11)
`
`P2—O23
`P2—O24
`N1—C1
`N2—C2
`N3—C3
`
`1.5831 (11)
`1.5836 (11)
`1.4859 (19)
`1.485 (2)
`1.490 (2)
`
`Table 2
`Hydrogen-bonding geometry (A˚ , (cid:14)), including weak C—H(cid:1)(cid:1)(cid:1)O hydrogen
`bonds (Desiraju & Steiner, 1999).
`
`D—H(cid:1)(cid:1)(cid:1)A
`O14—HO14(cid:1)(cid:1)(cid:1)O21
`O23—HO23(cid:1)(cid:1)(cid:1)O12i
`O24—HO24(cid:1)(cid:1)(cid:1)O11ii
`N1—H2N1(cid:1)(cid:1)(cid:1)O13iii
`N1—H1N1(cid:1)(cid:1)(cid:1)O13
`N1—H3N1(cid:1)(cid:1)(cid:1)O12iv
`N2—H1N2(cid:1)(cid:1)(cid:1)O22
`N2—H3N2(cid:1)(cid:1)(cid:1)O22v
`N2—H2N2(cid:1)(cid:1)(cid:1)O13vi
`N3—H2N3(cid:1)(cid:1)(cid:1)O11
`N3—H1N3(cid:1)(cid:1)(cid:1)O12iv
`N3—H3N3(cid:1)(cid:1)(cid:1)O11i
`C2—H1C2(cid:1)(cid:1)(cid:1)O14vi
`C2—H2C2(cid:1)(cid:1)(cid:1)O22vii
`C3—H3C3(cid:1)(cid:1)(cid:1)O21iv
`
`D—H
`
`H(cid:1)(cid:1)(cid:1)A
`
`D(cid:1)(cid:1)(cid:1)A
`
`D—H(cid:1)(cid:1)(cid:1)A
`
`2.5366 (16)
`159.5 (5)
`1.752 (6)
`0.820 (8)
`2.5785 (14)
`167.7 (7)
`1.771 (9)
`0.820 (10)
`2.5735 (15)
`168.3 (12)
`1.765 (12)
`0.820 (11)
`2.7677 (16)
`154
`1.94
`0.89
`2.7825 (16)
`168
`1.91
`0.89
`2.8337 (16)
`177
`1.94
`0.89
`2.7916 (17)
`172
`1.91
`0.89
`2.7437 (16)
`173
`1.86
`0.89
`2.8141 (15)
`175
`1.93
`0.89
`2.9416 (17)
`163
`2.08
`0.89
`2.8044 (18)
`173
`1.92
`0.89
`2.9967 (18)
`134
`2.31
`0.89
`3.2310 (19)
`130
`2.53
`0.96
`3.3347 (19)
`137
`2.56
`0.96
`3.243 (2)
`126
`2.58
`0.96
`2 (cid:255) z; (ii) 12 (cid:255) x; y (cid:255) 12; 1 2 (cid:255) x; 12 (cid:135) y; 12 (cid:255) z; (iii) (cid:255)x; 1 (cid:255) y; 1 (cid:255) z; (iv)
`
`
`
`
`
`Symmetry codes: (i) 1
`x; y (cid:255) 1; z; (v) 3
`
`
`
`
`
`
`2 (cid:255) z.2 (cid:255) x; y (cid:255) 12 (cid:255) x; 12 (cid:135) y; 12 (cid:255) z; (vi) 12 (cid:135) x; 32 (cid:255) y; z (cid:255) 12; (vii) 3 2; 1
`
`
`
`Although all H atoms could be found in the difference Fourier
`map and their positions and isotropic displacement parameters
`refined in the final model, some parameters regarding the H atoms
`were constrained or restrained as follows. The methylammonium H
`atoms were constrained and ideal geometry was assumed, with C—H
`and N—H bond lengths of 0.96 and 0.89 A˚ , respectively. The O—H
`
`Acta Cryst. (2006). C62, o73–o75
`
`Merck Exhibit 2216, Page 2
`Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp.
`IPR2020-00040
`
`

`

`bond lengths were restrained to 0.82 (1) A˚ and the P—O—H angles
`were restrained to 109.47 (1)(cid:14). For all H atoms, Uiso(H) =
`1.5Ueq(parent). The structure was examined for rotational disorder in
`the methyl and ammonium groups and there was no evidence for
`disorder on analysis of the difference maps and refinement results. A
`search of the Cambridge Structural Database (Version 5.26; Allen,
`2002) revealed that disorder of methylammonium molecules or their
`groups usually corresponds to structures where no or only weak
`hydrogen bonds are present, such as between halogen groups. As
`examples, (CH3NH3)[HgCl3] in the determinations with refcodes
`QQQBVJ04 and QQQBVJ31 have disordered methyl groups (Korfer
`& Fuess, 1988).
`Data collection: Crysalis CCD (Oxford Diffraction, 2005); cell
`refinement: Crysalis RED (Oxford Diffraction, 2005); data reduction:
`Crysalis RED; program(s) used to solve structure: SIR97 (Altomare
`et al., 1999); program(s) used to refine structure: JANA2000 (Petrˇı´cˇek
`& Dusˇek, 2000); molecular graphics: ORTEP-3 for Windows
`(Farrugia, 1997) and PLATON (Spek, 2003); software used to
`prepare material for publication: JANA2000.
`
`Miss Karla Fejfarova´
`is thanked for her help during the
`measurements. The support of this study by grant Nos. 203/02/
`0436 and 202/05/0421 of the Grant Agency of the Czech
`Republic and by grant No. 158/2004/B-CH/PrF is gratefully
`acknowledged.
`
`Supplementary data for this paper are available from the IUCr electronic
`archives (Reference: GG1289). Services for accessing these data are
`described at the back of the journal.
`
`organic compounds
`
`References
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`Acta Cryst. (2006). C62, o73–o75
`
`Jan Fa´bry et al.
`
`
`
`(cid:15) 3CH6N+(cid:1)HPO42(cid:255)(cid:1)H2PO4
`(cid:255) o75
`
`Merck Exhibit 2216, Page 3
`Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp.
`IPR2020-00040
`
`