Reassessment of paracetamol ortho­rhom­bic Form III and determination of a novel low-temperature monoclinic Form III-m from powder diffraction data

Reiss, C.A.; Mechelen, J.B. van; Goubitz, K.; Peschar, R.

doi:10.1107/S2053229618002619

Reassessment of paracetamol orthorhombic Form III and determination of a novel low-temperature monoclinic Form III-m from powder diffraction data

C. A. Reiss, J. B. van Mechelen, K. Goubitz and R. Peschar

Paracetamol [N-(4-hydroxyphenyl)acetamide, C₈H₉NO₂] has several polymorphs, just like many other drugs. The most stable polymorphs, denoted Forms I and II, can be obtained easily and their crystal structures are known. Crystals of the orthorhombic, less stable, room-temperature Form III are difficult to grow; they need a special recipe to crystallize and suffer from severe preferred orientation. A crystal structure model of Form III has been proposed and solved from a combination of structure prediction and powder X-ray diffraction (PXRD) [Perrin et al. (2009). Chem. Commun. 22, 3181–3183]. The final R_wp value of 0.138 and the corresponding considerable residual trace were reasons to check its validity. A new structure determination of Form III using new high-resolution PXRD data led to a final R_wp value of 0.042 and an improvement of the earlier proposed model. In addition, a reversible phase transition was found at 170–220 K between the orthorhombic Form III and a novel monoclinic Form III-m. The crystal structure of Form III-m has been determined and refined from PXRD data to a final R_wp value of 0.059.

Keywords: powder diffraction; paracetamol; acetaminophen; polymorph; PXRD; reversible phase transition; Rietveld refinement; crystal structure; reassessment; Monte Carlo; structure prediction; antipyretic; analgesic.

Read article Similar articles

Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S2053229618002619/sk3670sup1.cif Contains datablocks global, FORMIII-100K-4MOL-TR_publ, FORMIII-PCA21-NPLANE_publ
	Structure factor file (CIF format) https://doi.org/10.1107/S2053229618002619/sk3670FORMIII-100K-4MOL-TR_publsup2.hkl Contains datablock FORMIII-100K-4MOL-TR_publ
	MDL mol file https://doi.org/10.1107/S2053229618002619/sk3670FORMIII-100K-4MOL-TR_publsup3.mol Supplementary material
	Chemical Markup Language (CML) file https://doi.org/10.1107/S2053229618002619/sk3670FORMIII-100K-4MOL-TR_publsup6.cml Supplementary material
	Structure factor file (CIF format) https://doi.org/10.1107/S2053229618002619/sk3670FORMIII-PCA21-NPLANE_publsup4.hkl Contains datablock FORMIII-PCA21-NPLANE_publ
	MDL mol file https://doi.org/10.1107/S2053229618002619/sk3670FORMIII-PCA21-NPLANE_publsup5.mol Supplementary material

CCDC references: 1823732; 1823731

Computing details top

Program(s) used to refine structure: GSAS (Larson & Von Dreele, 1994) for FORMIII-100K-4MOL-TR_publ; GSAS for FORMIII-PCA21-NPLANE_publ.

N-(4-Hydroxyphenyl)acetamid (FORMIII-100K-4MOL-TR_publ) top

Crystal data top

C₈H₉NO₂	V = 1454.99 (9) Å³
M_r = 151.16	Z = 8
Monoclinic, Pc11	D_x = 1.38 Mg m⁻³
Hall symbol: P -2xc	Cu Kα radiation, λ = 1.5418 Å
a = 11.7546 (3) Å	T = 100 K
b = 8.5720 (3) Å	Particle morphology: powder
c = 14.5155 (5) Å	colourless
β = 90°	cylinder, 15 × 0.7 mm

Data collection top

PANalytical X'Pert Pro MPD diffractometer	Data collection mode: transmission
Radiation source: sealed X-ray tube, PANalytical Cu LFF	Scan method: step
Specimen mounting: glass capillary	2θ_min = 4.998°, 2θ_max = 59.975°, 2θ_step = 0.013°

Refinement top

Least-squares matrix: full	268 parameters
R_p = 0.045	255 restraints
R_wp = 0.059	Only H-atom coordinates refined
R_exp = 0.010	(Δ/σ)_max = 0.40
R(F²) = 0.04111	Background function: GSAS Background function number 1 with 9 terms. Shifted Chebyshev function of 1st kind 1: 5622.69 2: -4042.75 3: 832.560 4: 171.284 5: 18.7131 6: -408.715 7: 266.392 8: 55.8981 9: -93.0254
4230 data points	Preferred orientation correction: March-Dollase AXIS 1 Ratio= 1.539 Frac 0.869 h= 0.000 k= 0.000 l= 1.000 AXIS 2 Ratio= 1.000 Frac 0.131 h= 0.000 k= 0.000 l= 1.000 Prefered orientation correction range: Min= 0.36881, Max= 1.79136 Dollase, W. A. (1986). J. Appl. Cryst. 19, 267–272.
Profile function: CW Profile function number 4 with 21 terms Pseudovoigt profile coefficients as parameterized in P. Thompson, D.E. Cox & J.B. Hastings (1987). J. Appl. Cryst.,20,79-83. Asymmetry correction of L.W. Finger, D.E. Cox & A. P. Jephcoat (1994). J. Appl. Cryst.,27,892-900. Microstrain broadening by P.W. Stephens, (1999). J. Appl. Cryst.,32,281-289. #1(GU) = 551.589 #2(GV) = -2.176 #3(GW) = 4.056 #4(GP) = 0.000 #5(LX) = 7.226 #6(ptec) = 0.00 #7(trns) = 0.00 #8(shft) = 0.0000 #9(sfec) = 0.00 #10(S/L) = 0.0005 #11(H/L) = 0.0005 #12(eta) = 0.5925 #13(S400 ) = 2.1E-05 #14(S040 ) = 1.4E-05 #15(S004 ) = 2.5E-02 #16(S220 ) = 4.5E-04 #17(S202 ) = 6.5E-01 #18(S022 ) = 6.5E+00 #19(S013 ) = 1.2E+00 #20(S031 ) = -2.2E+00 #21(S211 ) = -3.3E-01 Peak tails are ignored where the intensity is below 0.0050 times the peak Aniso. broadening axis 0.0 1.0 0.0

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

	x	y	z	U_iso*/U_eq
C1	0.4430 (3)	−0.083 (3)	0.202 (3)	0.04737*
C2	0.3986 (4)	0.0414 (3)	0.2435 (3)	0.04737*
C3	0.4630 (4)	0.1762 (3)	0.2478 (3)	0.04737*
C4	0.5691 (3)	0.1873 (3)	0.2072 (3)	0.04737*
C5	0.6130 (4)	0.0611 (3)	0.1664 (3)	0.04737*
C6	0.5498 (4)	−0.0748 (3)	0.1637 (3)	0.04737*
O7	0.3796 (5)	−0.2179 (3)	0.1968 (3)	0.04737*
N8	0.6314 (4)	0.3276 (3)	0.2167 (3)	0.04737*
C9	0.5952 (3)	0.4733 (3)	0.2311 (3)	0.04737*
C10	0.6907 (4)	0.5860 (3)	0.2475 (3)	0.04737*
O11	0.4949 (4)	0.5108 (4)	0.2313 (4)	0.04737*
H21	0.3245 (9)	0.0331 (4)	0.2700 (4)	0.09464*
H31	0.4327 (12)	0.2618 (4)	0.2762 (4)	0.09464*
H51	0.6875 (9)	0.0662 (4)	0.1404 (4)	0.09464*
H61	0.5795 (12)	−0.1592 (4)	0.1340 (4)	0.09464*
H71	0.4153 (16)	−0.2802 (4)	0.1548 (4)	0.09464*
H81	0.7121 (9)	0.3146 (4)	0.2183 (4)	0.09464*
H101	0.7403 (12)	0.5962 (4)	0.1954 (4)	0.09464*
H102	0.7334 (12)	0.5474 (4)	0.3008 (4)	0.09464*
H103	0.6592 (13)	0.6849 (4)	0.2570 (4)	0.09464*
C21	0.1677 (3)	0.5931 (3)	−0.0228 (3)	0.04737*
C22	0.1272 (4)	0.4571 (3)	−0.0547 (3)	0.04737*
C23	0.1960 (3)	0.3240 (3)	−0.0500 (3)	0.04737*
C24	0.3039 (3)	0.3277 (3)	−0.0132 (3)	0.04737*
C25	0.3435 (4)	0.4637 (3)	0.0195 (3)	0.04737*
C26	0.2752 (3)	0.5963 (3)	0.0149 (3)	0.04737*
O27	0.1005 (5)	0.7257 (4)	−0.0258 (4)	0.04737*
N28	0.3698 (4)	0.1877 (3)	−0.0137 (3)	0.04737*
C29	0.3412 (3)	0.0421 (3)	−0.0350 (3)	0.04737*
C30	0.4425 (4)	−0.0609 (4)	−0.0525 (3)	0.04737*
O31	0.2428 (4)	−0.0029 (4)	−0.0409 (4)	0.04737*
H221	0.0524 (9)	0.4567 (4)	−0.0803 (4)	0.09464*
H231	0.1686 (12)	0.2317 (4)	−0.0732 (4)	0.09464*
H251	0.4185 (9)	0.4680 (4)	0.0444 (4)	0.09464*
H261	0.3020 (12)	0.6889 (4)	0.0368 (4)	0.09464*
H271	0.1476 (13)	0.8161 (4)	−0.0298 (4)	0.09464*
H281	0.4497 (9)	0.2057 (4)	−0.0121 (4)	0.09464*
H301	0.4862 (12)	−0.0150 (4)	−0.1033 (4)	0.09464*
H302	0.4898 (12)	−0.0751 (4)	0.0011 (4)	0.09464*
H303	0.4157 (14)	−0.1601 (4)	−0.0668 (4)	0.09464*
C41	−0.0569 (3)	1.0965 (3)	0.2257 (3)	0.04737*
C42	−0.0988 (4)	0.9542 (3)	0.2643 (3)	0.04737*
C43	−0.0355 (4)	0.8191 (3)	0.2591 (3)	0.04737*
C44	0.0693 (3)	0.8296 (3)	0.2140 (3)	0.04737*
C45	0.1092 (4)	0.9737 (3)	0.1750 (3)	0.04737*
C46	0.0455 (4)	1.1084 (3)	0.1803 (3)	0.04737*
O47	−0.1203 (5)	1.2302 (4)	0.2296 (4)	0.04737*
N48	0.1325 (4)	0.6867 (3)	0.2139 (3)	0.04737*
C49	0.1023 (3)	0.5385 (3)	0.2439 (3)	0.04737*
C50	0.2020 (4)	0.4337 (4)	0.2759 (3)	0.04737*
O51	0.0037 (4)	0.4921 (4)	0.2431 (4)	0.04737*
H421	−0.1711 (9)	0.9495 (4)	0.2946 (4)	0.09464*
H431	−0.0637 (11)	0.7216 (4)	0.2867 (4)	0.09464*
H451	0.1814 (9)	0.9818 (4)	0.1451 (4)	0.09464*
H461	0.0727 (11)	1.2068 (4)	0.1540 (4)	0.09464*
H471	−0.0714 (12)	1.3189 (4)	0.2194 (4)	0.09464*
H481	0.2130 (9)	0.7015 (4)	0.2187 (4)	0.09464*
H501	0.2553 (11)	0.4298 (4)	0.2266 (4)	0.09464*
H502	0.2393 (13)	0.4729 (4)	0.3269 (4)	0.09464*
H503	0.1746 (14)	0.3304 (4)	0.2951 (4)	0.09464*
C61	0.6792 (3)	0.4224 (3)	−0.0244 (3)	0.04737*
C62	0.6380 (4)	0.5650 (3)	−0.0625 (3)	0.04737*
C63	0.6996 (4)	0.7006 (3)	−0.0536 (3)	0.04737*
C64	0.8017 (3)	0.6915 (3)	−0.0062 (3)	0.04737*
C65	0.8421 (4)	0.5481 (3)	0.0324 (3)	0.04737*
C66	0.7805 (4)	0.4124 (3)	0.0233 (3)	0.04737*
O67	0.6197 (5)	0.2865 (3)	−0.0321 (3)	0.04737*
N68	0.8614 (4)	0.8359 (3)	−0.0035 (3)	0.04737*
C69	0.8256 (3)	0.9835 (3)	−0.0304 (3)	0.04737*
C70	0.9196 (4)	1.1049 (3)	−0.0454 (3)	0.04737*
O71	0.7254 (4)	1.0155 (4)	−0.0402 (4)	0.04737*
H621	0.5674 (8)	0.5701 (4)	−0.0950 (3)	0.09464*
H631	0.6720 (10)	0.7990 (4)	−0.0808 (3)	0.09464*
H651	0.9131 (8)	0.5414 (4)	0.0643 (3)	0.09464*
H661	0.8078 (10)	0.3136 (4)	0.0496 (3)	0.09464*
H671	0.6667 (13)	0.2000 (4)	−0.0109 (4)	0.09464*
H681	0.9422 (9)	0.8250 (4)	0.0019 (4)	0.09464*
H701	0.9706 (11)	1.0776 (4)	−0.0923 (4)	0.09464*
H702	0.9613 (12)	1.1095 (4)	0.0106 (4)	0.09464*
H703	0.8863 (13)	1.2047 (4)	−0.0637 (4)	0.09464*

Geometric parameters (Å, º) top

C1—C2	1.38 (3)	C41—C46	1.371 (6)
C1—C6	1.374 (18)	C41—O47	1.373 (5)
C1—O7	1.38 (2)	C42—C43	1.385 (5)
C2—C3	1.389 (5)	C42—H421	0.956 (10)
C2—H21	0.952 (11)	C43—C44	1.394 (6)
C3—C4	1.378 (6)	C43—H431	0.949 (7)
C3—H31	0.947 (8)	C44—C45	1.387 (4)
C4—C5	1.385 (5)	C44—N48	1.433 (4)
C4—N8	1.427 (4)	C45—C46	1.385 (5)
C5—C6	1.385 (5)	C45—H451	0.952 (10)
C5—H51	0.954 (11)	C46—H461	0.945 (6)
C6—H61	0.946 (8)	O47—H471	0.953 (10)
O7—H71	0.948 (10)	N48—C49	1.348 (4)
N8—C9	1.356 (4)	N48—H481	0.957 (11)
N8—H81	0.954 (11)	C49—C50	1.520 (5)
C9—C10	1.515 (5)	C49—O51	1.226 (6)
C9—O11	1.222 (6)	C50—H501	0.954 (11)
C10—H101	0.952 (10)	C50—H502	0.952 (9)
C10—H102	0.952 (10)	C50—H503	0.956 (7)
C10—H103	0.948 (8)	C61—C62	1.377 (4)
C21—C22	1.381 (5)	C61—C66	1.375 (6)
C21—C26	1.378 (6)	C61—O67	1.373 (5)
C21—O27	1.382 (5)	C62—C63	1.387 (5)
C22—C23	1.394 (5)	C62—H621	0.953 (10)
C22—H221	0.955 (11)	C63—C64	1.382 (6)
C23—C24	1.378 (6)	C63—H631	0.951 (6)
C23—H231	0.948 (7)	C64—C65	1.382 (4)
C24—C25	1.384 (5)	C64—N68	1.426 (4)
C25—C26	1.388 (5)	C65—C66	1.388 (5)
C25—H251	0.955 (11)	C65—H651	0.954 (10)
C26—H261	0.939 (7)	C66—H661	0.949 (6)
O27—H271	0.950 (10)	O67—H671	0.951 (10)
N28—C29	1.358 (4)	N68—C69	1.353 (4)
N28—H281	0.952 (11)	N68—H681	0.957 (11)
C29—C30	1.519 (5)	C69—C70	1.518 (5)
C29—O31	1.225 (6)	C69—O71	1.214 (6)
C30—H301	0.950 (10)	C70—H701	0.954 (10)
C30—H302	0.954 (10)	C70—H702	0.954 (10)
C30—H303	0.950 (7)	C70—H703	0.954 (8)
C41—C42	1.380 (4)

C2—C1—C6	120.6 (17)	C42—C41—C46	121.9 (3)
C2—C1—O7	120.6 (12)	C42—C41—O47	119.8 (4)
C6—C1—O7	119 (2)	C46—C41—O47	118.4 (3)
C1—C2—C3	119.9 (7)	C41—C42—C43	119.7 (4)
C1—C2—H21	119.5 (7)	C41—C42—H421	119.8 (4)
C3—C2—H21	120.6 (4)	C43—C42—H421	120.4 (4)
C2—C3—C4	119.7 (3)	C42—C43—C44	119.1 (3)
C2—C3—H31	120.0 (8)	C42—C43—H431	119.7 (8)
C4—C3—H31	120.2 (8)	C44—C43—H431	121.3 (7)
C3—C4—C5	119.8 (3)	C43—C44—C45	120.2 (3)
C3—C4—N8	116.5 (3)	C43—C44—N48	116.4 (3)
C5—C4—N8	123.5 (4)	C45—C44—N48	123.4 (4)
C4—C5—C6	120.6 (4)	C44—C45—C46	120.5 (4)
C4—C5—H51	120.3 (4)	C44—C45—H451	120.5 (4)
C6—C5—H51	119.1 (4)	C46—C45—H451	119.0 (4)
C1—C6—C5	119.3 (13)	C41—C46—C45	118.7 (3)
C1—C6—H61	120.6 (15)	C41—C46—H461	120.7 (7)
C5—C6—H61	120.0 (8)	C45—C46—H461	120.6 (8)
C1—O7—H71	108.9 (16)	C41—O47—H471	108.8 (8)
C4—N8—C9	130.7 (4)	C44—N48—C49	129.8 (4)
C4—N8—H81	114.5 (4)	C44—N48—H481	113.1 (4)
C9—N8—H81	114.5 (4)	C49—N48—H481	111.4 (4)
N8—C9—C10	113.8 (3)	N48—C49—C50	113.8 (3)
N8—C9—O11	123.3 (4)	N48—C49—O51	122.8 (4)
C10—C9—O11	122.9 (3)	C50—C49—O51	123.3 (3)
C9—C10—H101	109.7 (6)	C49—C50—H501	110.0 (6)
C9—C10—H102	110.1 (6)	C49—C50—H502	110.4 (7)
C9—C10—H103	109.1 (10)	C49—C50—H503	109.3 (10)
H101—C10—H102	108.6 (11)	H501—C50—H502	108.9 (11)
H101—C10—H103	110.1 (7)	H501—C50—H503	109.8 (7)
H102—C10—H103	109.3 (7)	H502—C50—H503	108.5 (7)
C22—C21—C26	120.1 (3)	C62—C61—C66	120.9 (3)
C22—C21—O27	120.8 (4)	C62—C61—O67	120.9 (4)
C26—C21—O27	119.1 (3)	C66—C61—O67	118.2 (3)
C21—C22—C23	119.8 (4)	C61—C62—C63	119.8 (4)
C21—C22—H221	119.0 (4)	C61—C62—H621	120.0 (4)
C23—C22—H221	121.1 (4)	C63—C62—H621	120.2 (4)
C22—C23—C24	120.1 (3)	C62—C63—C64	119.6 (3)
C22—C23—H231	119.7 (8)	C62—C63—H631	120.0 (7)
C24—C23—H231	120.2 (8)	C64—C63—H631	120.4 (7)
C23—C24—C25	119.8 (3)	C63—C64—C65	120.2 (3)
C23—C24—N28	116.4 (3)	C63—C64—N68	115.8 (3)
C25—C24—N28	123.8 (4)	C65—C64—N68	123.9 (4)
C24—C25—C26	120.2 (4)	C64—C65—C66	120.1 (4)
C24—C25—H251	120.5 (4)	C64—C65—H651	120.3 (4)
C26—C25—H251	119.3 (4)	C66—C65—H651	119.6 (4)
C21—C26—C25	120.0 (3)	C61—C66—C65	119.3 (3)
C21—C26—H261	119.6 (8)	C61—C66—H661	120.2 (7)
C25—C26—H261	120.4 (8)	C65—C66—H661	120.5 (7)
C21—O27—H271	109.4 (9)	C61—O67—H671	108.5 (8)
C24—N28—C29	131.2 (4)	C64—N68—C69	128.9 (4)
C24—N28—H281	113.3 (4)	C64—N68—H681	114.4 (4)
C29—N28—H281	113.9 (4)	C69—N68—H681	114.4 (4)
N28—C29—C30	114.0 (3)	N68—C69—C70	115.0 (3)
N28—C29—O31	123.6 (4)	N68—C69—O71	121.9 (3)
C30—C29—O31	122.4 (3)	C70—C69—O71	123.0 (3)
C29—C30—H301	110.5 (7)	C69—C70—H701	110.2 (6)
C29—C30—H302	110.4 (7)	C69—C70—H702	109.9 (6)
C29—C30—H303	109.0 (10)	C69—C70—H703	108.9 (9)
H301—C30—H302	109.0 (11)	H701—C70—H702	108.6 (11)
H301—C30—H303	108.6 (7)	H701—C70—H703	109.6 (7)
H302—C30—H303	109.2 (7)	H702—C70—H703	109.5 (7)

N-(4-Hydroxyphenyl)acetamid (FORMIII-PCA21-NPLANE_publ) top

Crystal data top

C₈H₉NO₂	Z = 8
M_r = 151.16	D_x = 1.336 Mg m⁻³
Orthorhombic, Pca2₁	Cu Kα radiation, λ = 1.5418 Å
Hall symbol: P 2c -2ac	T = 293 K
a = 11.8376 (3) Å	Particle morphology: powder
b = 8.5688 (3) Å	colourless
c = 14.81837 (16) Å	cylinder, 15 × 0.7 mm
V = 1503.09 (7) Å³

Data collection top

PANalytical X'Pert Pro MPD diffractometer	Data collection mode: transmission
Radiation source: sealed X-ray tube, PANalytical Cu LFF	Scan method: step
Specimen mounting: glass capillary	2θ_min = 0.983°, 2θ_max = 59.967°, 2θ_step = 0.008°

Refinement top

Least-squares matrix: full	152 parameters
R_p = 0.031	131 restraints
R_wp = 0.042	Only H-atom coordinates refined
R_exp = 0.010	(Δ/σ)_max = 0.07
R(F²) = 0.03900	Background function: GSAS Background function number 1 with 16 terms. Shifted Chebyshev function of 1st kind 1: 7766.23 2: -5328.32 3: -324.317 4: 1110.79 5: -126.875 6: -500.584 7: 112.527 8: 479.653 9: -339.782 10: -24.0167 11: 82.6839 12: -38.4167 13: -17.2172 14: 49.5366 15: 35.3569 16: -110.026
7374 data points	Preferred orientation correction: March-Dollase AXIS 1 Ratio= 1.07254 h= 0.000 k= 0.000 l= 1.000 Prefered orientation correction range: Min= 0.81052, Max= 1.11075
Profile function: CW Profile function number 4 with 18 terms Pseudovoigt profile coefficients as parameterized in P. Thompson, D.E. Cox & J.B. Hastings (1987). J. Appl. Cryst.,20,79-83. Asymmetry correction of L.W. Finger, D.E. Cox & A. P. Jephcoat (1994). J. Appl. Cryst.,27,892-900. Microstrain broadening by P.W. Stephens, (1999). J. Appl. Cryst.,32,281-289. #1(GU) = 288.800 #2(GV) = -0.117 #3(GW) = 12.617 #4(GP) = 0.000 #5(LX) = 4.245 #6(ptec) = 0.00 #7(trns) = 0.00 #8(shft) = 0.0000 #9(sfec) = 0.00 #10(S/L) = 0.0005 #11(H/L) = 0.0005 #12(eta) = 0.8231 #13(S400 ) = 1.8E-02 #14(S040 ) = 3.2E-02 #15(S004 ) = 2.1E-02 #16(S220 ) = 7.6E-02 #17(S202 ) = 1.3E-01 #18(S022 ) = 1.4E+01 Peak tails are ignored where the intensity is below 0.0050 times the peak Aniso. broadening axis 1.0 1.0 1.0

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

	x	y	z	U_iso*/U_eq
C1	0.4221 (2)	−0.0931 (3)	0.2812 (14)	0.0685*
C2	0.3784 (3)	0.0450 (3)	0.25041 (19)	0.0685*
C3	0.4438 (3)	0.1783 (4)	0.2543 (2)	0.0685*
C4	0.5529 (2)	0.1734 (3)	0.28866 (19)	0.0685*
C5	0.5961 (3)	0.0331 (3)	0.32047 (19)	0.0685*
C6	0.5301 (3)	−0.0994 (3)	0.31642 (18)	0.0685*
O7	0.3569 (3)	−0.2259 (4)	0.2787 (2)	0.0685*
N8	0.6156 (3)	0.3174 (3)	0.2861 (2)	0.0685*
C9	0.5800 (2)	0.4632 (3)	0.2685 (2)	0.0685*
C10	0.6718 (3)	0.5745 (4)	0.24012 (19)	0.0685*
O11	0.4808 (3)	0.4995 (8)	0.2744 (2)	0.0685*
H21	0.3042 (6)	0.0481 (13)	0.2271 (2)	0.1369*
H31	0.4132 (8)	0.2729 (9)	0.2317 (2)	0.1369*
H51	0.6707 (6)	0.0251 (13)	0.3436 (2)	0.1369*
H61	0.5614 (8)	−0.1942 (9)	0.3380 (2)	0.1369*
H71	0.4007 (10)	−0.3154 (11)	0.2925 (3)	0.1369*
H81	0.6949 (7)	0.3026 (14)	0.2764 (3)	0.1369*
H101	0.7261 (8)	0.5831 (16)	0.2865 (3)	0.1369*
H102	0.7062 (10)	0.5364 (15)	0.1869 (3)	0.1369*
H103	0.6399 (10)	0.6742 (9)	0.2298 (3)	0.1369*
C21	0.8151 (2)	0.5947 (3)	0.01786 (18)	0.0685*
C22	0.8565 (3)	0.4656 (3)	0.06185 (19)	0.0685*
C23	0.7923 (3)	0.3297 (4)	0.06202 (19)	0.0685*
C24	0.6873 (2)	0.3214 (3)	0.01772 (19)	0.0685*
C25	0.6496 (3)	0.4545 (3)	−0.02617 (18)	0.0685*
C26	0.7131 (3)	0.5899 (4)	−0.02582 (19)	0.0685*
O27	0.8732 (3)	0.7319 (4)	0.0147 (2)	0.0685*
N28	0.6198 (3)	0.1783 (3)	0.0220 (2)	0.0685*
C29	0.6446 (2)	0.0268 (3)	0.0415 (2)	0.0685*
C30	0.5444 (3)	−0.0827 (4)	0.0525 (2)	0.0685*
O31	0.7421 (3)	−0.0205 (5)	0.0427 (3)	0.0685*
H221	0.9268 (6)	0.4693 (12)	0.0918 (2)	0.1369*
H231	0.8225 (7)	0.2427 (9)	0.0938 (2)	0.1369*
H251	0.5788 (6)	0.4566 (13)	−0.0564 (2)	0.1369*
H261	0.6857 (8)	0.6797 (9)	−0.0564 (2)	0.1369*
H271	0.8231 (9)	0.8143 (11)	−0.0008 (3)	0.1369*
H281	0.5410 (6)	0.2005 (14)	0.0217 (3)	0.1369*
H301	0.4998 (9)	−0.0506 (15)	0.1021 (3)	0.1369*
H302	0.4983 (9)	−0.0853 (17)	0.0002 (3)	0.1369*
H303	0.5713 (11)	−0.1848 (9)	0.0642 (3)	0.1369*

Geometric parameters (Å, º) top

C1—C2	1.369 (8)	C21—C22	1.373 (4)
C1—C6	1.381 (9)	C21—C26	1.370 (4)
C1—O7	1.376 (5)	C21—O27	1.363 (4)
C2—C3	1.381 (4)	C22—C23	1.391 (4)
C2—H21	0.944 (8)	C22—H221	0.944 (7)
C3—C4	1.388 (4)	C23—C24	1.407 (4)
C3—H31	0.949 (9)	C23—H231	0.952 (8)
C4—C5	1.389 (4)	C24—C25	1.387 (4)
C4—N8	1.441 (4)	C24—N28	1.466 (4)
C5—C6	1.380 (4)	C25—C26	1.383 (4)
C5—H51	0.950 (8)	C25—H251	0.950 (7)
C6—H61	0.949 (8)	C26—H261	0.950 (8)
O7—H71	0.948 (10)	O27—H271	0.950 (10)
N8—C9	1.345 (4)	N28—C29	1.362 (4)
N8—H81	0.957 (8)	N28—H281	0.952 (8)
C9—C10	1.506 (4)	C29—C30	1.521 (4)
C9—O11	1.218 (4)	C29—O31	1.223 (4)
C10—H101	0.944 (8)	C30—H301	0.945 (8)
C10—H102	0.946 (8)	C30—H302	0.948 (8)
C10—H103	0.946 (9)	C30—H303	0.947 (9)

C2—C1—C6	120.6 (3)	C22—C21—C26	121.0 (3)
C2—C1—O7	119.6 (6)	C22—C21—O27	122.1 (3)
C6—C1—O7	119.8 (6)	C26—C21—O27	117.0 (3)
C1—C2—C3	119.3 (4)	C21—C22—C23	118.7 (3)
C1—C2—H21	119.8 (8)	C21—C22—H221	120.7 (7)
C3—C2—H21	120.9 (7)	C23—C22—H221	120.6 (7)
C2—C3—C4	120.8 (3)	C22—C23—C24	121.6 (3)
C2—C3—H31	118.5 (6)	C22—C23—H231	116.9 (6)
C4—C3—H31	120.7 (6)	C24—C23—H231	121.5 (6)
C3—C4—C5	119.6 (3)	C23—C24—C25	117.5 (3)
C3—C4—N8	116.3 (3)	C23—C24—N28	120.2 (3)
C5—C4—N8	124.1 (3)	C25—C24—N28	122.2 (3)
C4—C5—C6	119.3 (3)	C24—C25—C26	120.9 (3)
C4—C5—H51	121.9 (7)	C24—C25—H251	121.4 (7)
C6—C5—H51	118.9 (7)	C26—C25—H251	117.7 (7)
C1—C6—C5	120.6 (3)	C21—C26—C25	120.4 (3)
C1—C6—H61	121.5 (6)	C21—C26—H261	120.2 (6)
C5—C6—H61	117.9 (6)	C25—C26—H261	119.5 (6)
C1—O7—H71	110.9 (8)	C21—O27—H271	109.5 (7)
C4—N8—C9	129.7 (3)	C24—N28—C29	133.6 (3)
C4—N8—H81	113.3 (8)	C24—N28—H281	111.5 (8)
C9—N8—H81	113.7 (8)	C29—N28—H281	113.8 (8)
N8—C9—C10	114.6 (3)	N28—C29—C30	116.2 (3)
N8—C9—O11	121.7 (4)	N28—C29—O31	121.5 (3)
C10—C9—O11	123.7 (4)	C30—C29—O31	122.0 (3)
C9—C10—H101	109.7 (7)	C29—C30—H301	109.9 (8)
C9—C10—H102	109.0 (8)	C29—C30—H302	112.1 (8)
C9—C10—H103	109.2 (7)	C29—C30—H303	109.0 (8)
H101—C10—H102	109.9 (9)	H301—C30—H302	108.7 (9)
H101—C10—H103	108.6 (10)	H301—C30—H303	108.4 (9)
H102—C10—H103	110.4 (8)	H302—C30—H303	108.7 (10)

Distance restraints applied to non-H atoms in the first molecule; identical distance restraints were applied to additional molecules top

Atom1	Atom2	Restraint (Å)	Atom1	Atom2	Restraint (Å)
C1	C2	1.38	C4	N8	1.42
C1	C6	1.38	C5	C6	1.39
C1	O7	1.38	N8	C9	1.34
C2	C3	1.39	C9	O11	1.22
C3	C4	1.38

Angular restraints applied to the first molecule; identical angular restraints were applied to additional molecules top

Atom1	Atom2	Atom3	Restraint (°)	Atom1	Atom2	Atom3	Restraint (°)
C1	C2	C3	120	H31	C3	C2	120
C2	C3	C4	120	H31	C3	C4	120
C4	C5	C6	120	H51	C5	C4	120
C5	C6	C1	120	H51	C5	C6	120
C6	C1	C2	120	H61	C6	C5	120
C6	C1	O7	119	H61	C6	C1	120
C2	C1	O7	121	H71	C7	C1	110
C3	C4	N8	116	H81	N8	C4	115
C5	C4	N8	124	H81	N8	C9	115
C4	N8	C9	130	H101	C10	C9	109
N8	C9	C10	115	H102	C10	C9	109
N8	C9	O11	122.5	H103	C10	C9	109
C10	C9	O11	122.5	H101	C10	H102	109
H21	C2	C1	120	H101	C10	H103	109
H21	C2	C3	120	H102	C10	H103	109

Comparison of structural data for the currently known forms of paracetamol top

Polymorph	Form 1^a	Form II^b	Form III-o^c	Form III-o^d	Form III-m^d
T (K)	330	298	300	293	100
Space Group	P2₁/a	Pcab	Pca2₁	Pca2₁	Pc11^e
Z(Z')	4(1)	8(1)	4(2)	4(2)	2(4)
a (Å)	12.872 (3)	7.405 (3)	11.837 (36)	11.8376 (3)	11.7546 (3)
b (Å)	9.370 (2)	11.831 (4)	8.560 (25)	8.5688 (3)	8.5720 (3)
c (Å)	7.085 (2)	17.156 (6)	14.819 (45)	14.81837 (16)	14.5155 (5)
α (°)	90.0	90	90	90	84.160 (14)
β (°)	115.62 (2)	90	90	90	90
δ (°)	90.0	90	90	90	90
V (Å³)	770.5	1503	1501.53	1503.09 (7)	1454.99 (9)
R_wp	0.052	nd	0.138	0.042	0.059
ρ (Mg m^-3)	1.303	1.336	1.337	1.336	1.380
Ave. (═O···HO)	2.66	2.73	2.60	2.77	2.72
Ave. (NH···OH)	2.93	2.97	3.05	2.99	3.02

References: (a) Wilson (2000); (b) Nichols & Frampton (1998); (c) Perrin et al. (2009). Notes: (d) this work, s.u. vlaues as calculated by GSAS (Larson & Von Dreele, 1994); (e) nonstandard setting because of relationship with Form III-o.

Hydrogen-bridging scheme (Å) for Form III-o top

No.	Type	D—H···A	D—H	H···A	D···A	D—H···A
1		O7—H71···O11ⁱ	0.948 (11)	1.868 (12)	2.773 (7)	158.9 (5)
2		N8—H81···O7ⁱⁱ	0.958 (9)	2.028 (9)	2.964 (5)	165.3 (9)
3		O27—H271···O31ⁱⁱⁱ	0.950 (10)	1.827 (10)	2.661 (5)	144.9 (5)
4		N28—H281···O27^iv	0.952 (8)	2.072 (8)	3.021 (5)	174.6 (9)
5	Intra	C3—H31···O11	0.949 (8)	2.193 (10)	2.803 (8)	121.0 (6)
6	Intra	C23—H231···O31	0.952 (8)	2.562 (9)	3.072 (5)	113.8 (5)

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

Hydrogen-bridging scheme (Å) for Form III-m top

No.	Type	D—H···A	D—H	H···A	D···A	D—H···A
1		O7—H71···O11ⁱ	0.948 (10)	2.217 (10)	2.694 (5)	110.1 (5)
2		N8—H81···O47ⁱⁱ	0.955 (12)	2.099 (11)	3.036 (7)	166.5 (4)
3		O27—H271···O31ⁱⁱⁱ	0.949 (10)	1.907 (10)	2.856 (6)	178.6 (7)
4		N28—H281···O67	0.952 (11)	2.125 (12)	3.061 (7)	167.2 (5)
5		O47—H471···O51ⁱⁱⁱ	0.953 (10)	1.791 (9)	2.701 (6)	158.7 (7)
6		N48—H481···O7ⁱⁱⁱ	0.958 (11)	2.090 (11)	3.021 (7)	163.4 (5)
7		O67—H671···O71ⁱ	0.950 (10)	1.845 (8)	2.648 (5)	144.6 (7)
8		N68—H681···O27^iv	0.957 (12)	2.102 (11)	2.963 (7)	154.3 (5)
9	Intra	C3—H31···O11	0.947 (7)	2.287 (7)	2.878 (4)	119.9 (8)
11	Intra	C23—H231···O31	0.947 (7)	2.198 (8)	2.864 (4)	124.6 (9)
13	Intra	C43—H431···O51	0.949 (7)	2.270 (7)	2.873 (4)	120.8 (8)
15	Intra	C63—H631···O71	0.951 (7)	2.100 (6)	2.743 (4)	123.6 (7)

Symmetry codes: (i) x, y-1, z; (ii) x+1, y-1, z; (iii) x, y+1, z; (iv) x+1, y, z.

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Text
		Plain Text

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Text
		Plain Text

Search IUCr Journals		doi		Advanced search
Author		volume	page

Reassessment of paracetamol ortho­rhom­bic Form III and determination of a novel low-temperature monoclinic Form III-m from powder diffraction data

Supporting information

Reassessment of paracetamol orthorhombic Form III and determination of a novel low-temperature monoclinic Form III-m from powder diffraction data