A paracetamol-morpholine adduct

Paracetamol [also known as acet­amino­phen or N-(4-hydroxy­phenyl)­acet­amide] is an important analgesic drug that has recently been cocrystallized with a series of cyclic N- and O-donor compounds. This paper describes the formation of a paracetamol adduct with morpholine, viz. paracetamol-morpholine (1/2.5), C₈H₉NO₂·2.5C₄H₉NO. There are five morpholine mol­ecules and two paracetamol mol­ecules in the unit cell. The paracetamol mol­ecules are held together by hydrogen bonding via morpholine mol­ecules, one of which is disordered about an inversion centre.

Key indicators

• Single-crystal X-ray study
• T = 150 K
• Mean [sigma](C-C) = 0.005 Å
• Disorder in solvent or counterion
• R factor = 0.054
• wR factor = 0.178
• Data-to-parameter ratio = 13.9

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry


 Alert Level C:



RADNW_01  Alert C The radiation wavelength lies outside the expected range
          for the supplied radiation type. Expected range 1.54175-1.54180
          Wavelength given =    1.54184

REFLT_03
         From the CIF: _diffrn_reflns_theta_max           70.30
         From the CIF: _reflns_number_total               3416
         TEST2: Reflns within _diffrn_reflns_theta_max
         Count of symmetry unique reflns         3712
         Completeness (_total/calc)             92.03%
          Alert C: < 95% complete

PLAT_302  Alert C Anion/Solvent Disorder .......................       8.00 Perc.

General Notes



ABSTM_02  When printed, the submitted absorption T values will be replaced
          by the scaled T values. Since the ratio of scaled T's is
          identical to the ratio of reported T values, the scaling does
          not imply a change to the absorption corrections used in the
          study.
          Ratio of Tmax expected/reported      1.076
          Tmax scaled      0.956 Tmin scaled      0.771


 0 Alert Level A = Potentially serious problem

 0 Alert Level B = Potential problem

 3 Alert Level C = Please check

---

Computing details

Data collection: DIF4 (Stoe & Cie, 1990); cell refinement: DIF4; data reduction: REDU4 (Stoe & Cie, 1990); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and CAMERON (Watkin et al., 1996).

N-(4-hydroxyphenyl)acetamide–morpholine (1/2.5)

Crystal data

C8H9NO2·2.5C4H9NO	Z = 2
Mr = 368.97	F(000) = 400
Triclinic, P1	Dx = 1.260 Mg m^−3
Hall symbol: -P 1	Cu Kα radiation, λ = 1.54184 Å
a = 8.710 (4) Å	Cell parameters from 48 reflections
b = 9.920 (5) Å	θ = 20–22°
c = 12.385 (5) Å	µ = 0.74 mm^−1
α = 102.35 (3)°	T = 150 K
β = 108.33 (2)°	Plate, colourless
γ = 96.68 (3)°	0.27 × 0.23 × 0.06 mm
V = 972.7 (7) Å^3

Data collection

Stoe Stadi-4 four-circle diffractometer	1951 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.028
Graphite monochromator	θmax = 70.3°, θmin = 3.9°
ω–θ scans	h = −10→10
Absorption correction: empirical (using intensity measurements) via ψ scans [SHELXTL (Sheldrick (2001) based on method of North et al. (1968)]	k = −12→11
Tmin = 0.717, Tmax = 0.889	l = −14→15
3596 measured reflections	3 standard reflections every 120 min
3416 independent reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: calc/difmap
R[F^2 > 2σ(F^2)] = 0.054	H-atom parameters constrained
wR(F^2) = 0.178	w = 1/[σ^2(Fo^2) + (0.0983P)^2 + 0.3346P] where P = (Fo^2 + 2Fc^2)/3
S = 1.03	(Δ/σ)max < 0.001
3416 reflections	Δρmax = 0.35 e Å^−3
246 parameters	Δρmin = −0.26 e Å^−3
0 restraints	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0077 (14)

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. #=============================================================================== # PLATON/CHECK-(191101) versus check.def version of 16/11/01 for entry: parmor # Data From: parmor_e.cif - Data Type: CIF Bond Precision C—C = 0.0047 A # # CELL 1.54184 8.710 9.920 12.385 102.35 108.33 96.68 972.70 # SpaceGroup from Symmetry P-1 Hall: –P 1 # Reported P-1 ? # MoietyFormula 2(C8 H9 N O2), 5(C4 H9 N O) # Reported (C8H9NO2)(C4H9NO)2.5 # SumFormula C36 H63 N7 O9 # Reported C18 H31.50 N3.50 O4.50 # Mr = 737.93[Calc], 368.97[Rep] # Dx,gcm-3 = 1.260[Calc], 1.260[Rep] # Z = 1[Calc], 2[Rep] # Mu (mm-1) = 0.743[Calc], 0.743[Rep] # F000 = 400.0[Calc], 400.0[Rep] # Reported T limits: Tmin=0.717 Tmax=0.889 'EMPIRICAL' # Calculated T limits: Tmin=0.818 Tmin'=0.818 Tmax=0.956 # Reported Hmax= 10, Kmax= 12, Lmax= 15, Nref= 3416, Th(max)= 70.30 # Calculated Hmax= 10, Kmax= 12, Lmax= 15, Nref= 3712 (3712), Ratio= 0.92 (0.92) # R= 0.0538 (1951), wR2= 0.1782 (3416), S = 1.031, Npar= 246 #=============================================================================== >>> The Following ALERTS were generated <<<

028_ALERT A -diffrn-measured-fraction-theta-max low ···.. 0.92 022_ALERT C Ratio Unique / Expected Reflections too Low.. 0.92 029_ALERT C -diffrn-measured-fraction-theta-full low ···.. 0.92

The data were collected on a four-circle using Cu-kα radiation. Certain regions of reciprocal space above 2θ=90° were shaded by the chi- circle, and this has resulted in a low -diffrn-measured-fraction-theta-max.

041_ALERT C Calc. and Rep. SumFormula Strings Differ.. ? 042_ALERT C Calc. and Rep. MoietyFormula Strings Differ.. ? 045_ALERT C Calculated and Reported Z differ by ·········. 0.50 Ratio

These reflect our choice of formula unit.

062_ALERT C Rescale T(min) & T(max) by ··················. 1.08

No action taken.

125_ALERT C No _symmetry_space_group_name_Hall given ···.. ?

Corrected.

302_ALERT C Anion/Solvent Disorder ·····················.. 8.00 Perc.

We know. See text.

340_ALERT C Low Bond Precision on C—C bonds (x 1000) Ang.. 5

Disordered structure.

790_ALERT C Centre of Gravity not Within Unit Cell: Resd.# 1 C8 H9 N O2

Fixed.

790_ALERT C Centre of Gravity not Within Unit Cell: Resd.# 2 C4 H9 N O 790_ALERT C Centre of Gravity not Within Unit Cell: Resd.# 3 C4 H9 N O 790_ALERT C Centre of Gravity not Within Unit Cell: Resd.# 4 C4 H9 N O

No action; the asymmetric unit was chosen to be discrete H-bonded fragment.

ALERT Level Summary 1 ALERT Level A = In General: Serious Problem 13 ALERT Level C = Check & Explain

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
O1	0.3543 (3)	0.9687 (3)	0.32398 (19)	0.0407 (6)
H11	0.268 (6)	0.901 (5)	0.249 (4)	0.081 (14)*
C1	0.4893 (4)	1.0247 (3)	0.3041 (2)	0.0325 (7)
C2	0.6318 (4)	1.0856 (3)	0.4007 (2)	0.0340 (7)
H2	0.6327	1.0862	0.4761	0.041*
C3	0.7720 (4)	1.1452 (3)	0.3858 (2)	0.0320 (7)
H3	0.8668	1.1852	0.4515	0.038*
C4	0.7745 (3)	1.1470 (3)	0.2738 (2)	0.0298 (7)
C5	0.6316 (4)	1.0851 (3)	0.1770 (2)	0.0337 (7)
H5	0.6303	1.0852	0.1017	0.040*
C6	0.4907 (4)	1.0231 (3)	0.1915 (3)	0.0360 (7)
H6	0.3967	0.9802	0.1258	0.043*
N1	0.9251 (3)	1.2109 (3)	0.2681 (2)	0.0339 (6)
H1	1.010 (4)	1.254 (4)	0.345 (3)	0.047 (10)*
C7	0.9630 (4)	1.2134 (3)	0.1705 (3)	0.0331 (7)
O2	0.8622 (3)	1.1677 (3)	0.06987 (17)	0.0441 (6)
C8	1.1411 (4)	1.2719 (4)	0.1936 (3)	0.0406 (8)
H8A	1.1982	1.1958	0.1826	0.061*
H8B	1.1912	1.3301	0.2731	0.061*
H8C	1.1475	1.3272	0.1397	0.061*
N1A	1.1842 (3)	1.3434 (3)	0.5029 (2)	0.0360 (6)
H1A1	1.130 (4)	1.349 (4)	0.554 (3)	0.067 (13)*
C2A	1.2627 (4)	1.4925 (4)	0.5329 (3)	0.0432 (8)
H2A1	1.1792	1.5496	0.5312	0.052*
H2A2	1.3087	1.5067	0.4734	0.052*
C3A	1.3979 (4)	1.5420 (4)	0.6527 (3)	0.0468 (9)
H3A2	1.4504	1.6386	0.6652	0.056*
H3A1	1.3505	1.5393	0.7135	0.056*
O4A	1.5182 (3)	1.4553 (3)	0.6615 (2)	0.0513 (7)
C5A	1.4447 (4)	1.3107 (4)	0.6411 (3)	0.0492 (9)
H5A1	1.3981	1.3019	0.7014	0.059*
H5A2	1.5288	1.2538	0.6463	0.059*
C6A	1.3114 (4)	1.2577 (4)	0.5214 (3)	0.0460 (8)
H6A2	1.3612	1.2564	0.4614	0.055*
H6A1	1.2598	1.1618	0.5118	0.055*
N1B	0.8948 (3)	1.2115 (3)	−0.1501 (2)	0.0369 (6)
H1B1	0.892 (5)	1.210 (4)	−0.0788 (17)	0.059 (11)*
C2B	1.0423 (4)	1.1576 (4)	−0.1578 (3)	0.0417 (8)
H2B1	1.0345	1.0628	−0.1485	0.050*
H2B2	1.1401	1.2167	−0.0956	0.050*
C3B	1.0541 (4)	1.1578 (4)	−0.2767 (3)	0.0419 (8)
H3B2	1.1515	1.1230	−0.2827	0.050*
H3B1	0.9584	1.0951	−0.3383	0.050*
O4B	1.0631 (3)	1.2961 (2)	−0.29388 (19)	0.0390 (6)
C5B	0.9246 (4)	1.3526 (4)	−0.2823 (3)	0.0402 (8)
H5B1	0.8251	1.2963	−0.3446	0.048*
H5B2	0.9361	1.4476	−0.2912	0.048*
C6B	0.9085 (4)	1.3549 (4)	−0.1638 (3)	0.0408 (8)
H6B2	1.0043	1.4159	−0.1011	0.049*
H6B1	0.8113	1.3911	−0.1592	0.049*
N1C	1.3689 (3)	1.4607 (3)	0.0409 (2)	0.0497 (7)	0.50
H1C1	1.430 (9)	1.511 (8)	0.115 (3)	0.074*	0.50
O1C	1.3689 (3)	1.4607 (3)	0.0409 (2)	0.0497 (7)	0.50
C2C	1.4703 (5)	1.3634 (5)	0.0125 (4)	0.0533 (10)
H2C2	1.429 (6)	1.311 (5)	−0.082 (4)	0.083 (14)*
H2C1	1.479 (5)	1.299 (4)	0.062 (4)	0.065 (12)*
C3C	1.6388 (5)	1.4367 (5)	0.0272 (4)	0.0526 (10)
H3CA	1.699 (5)	1.486 (4)	0.124 (4)	0.068 (12)*
H3CB	1.705 (5)	1.357 (4)	−0.004 (3)	0.057 (11)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0335 (12)	0.0548 (15)	0.0299 (11)	−0.0078 (10)	0.0122 (9)	0.0101 (10)
C1	0.0303 (15)	0.0399 (18)	0.0292 (15)	0.0033 (13)	0.0136 (12)	0.0102 (13)
C2	0.0354 (16)	0.0444 (18)	0.0207 (13)	0.0003 (14)	0.0104 (12)	0.0089 (12)
C3	0.0335 (15)	0.0375 (17)	0.0222 (14)	0.0024 (13)	0.0080 (12)	0.0076 (12)
C4	0.0270 (14)	0.0369 (17)	0.0269 (14)	0.0038 (12)	0.0112 (12)	0.0098 (12)
C5	0.0316 (15)	0.0457 (19)	0.0227 (14)	0.0017 (13)	0.0091 (12)	0.0110 (13)
C6	0.0330 (16)	0.0464 (19)	0.0242 (14)	−0.0020 (14)	0.0065 (12)	0.0106 (13)
N1	0.0304 (13)	0.0469 (16)	0.0248 (12)	0.0023 (12)	0.0106 (11)	0.0117 (11)
C7	0.0365 (16)	0.0383 (18)	0.0281 (15)	0.0033 (13)	0.0162 (13)	0.0111 (12)
O2	0.0371 (12)	0.0670 (16)	0.0249 (11)	−0.0043 (11)	0.0098 (9)	0.0151 (10)
C8	0.0318 (16)	0.054 (2)	0.0377 (17)	0.0009 (15)	0.0153 (14)	0.0145 (15)
N1A	0.0312 (13)	0.0473 (16)	0.0297 (13)	0.0008 (12)	0.0130 (11)	0.0110 (11)
C2A	0.0427 (18)	0.048 (2)	0.0371 (17)	0.0049 (16)	0.0104 (15)	0.0147 (15)
C3A	0.0444 (19)	0.049 (2)	0.0386 (18)	0.0010 (17)	0.0082 (15)	0.0090 (15)
O4A	0.0330 (12)	0.0593 (16)	0.0555 (15)	−0.0014 (11)	0.0059 (11)	0.0227 (12)
C5A	0.0384 (18)	0.057 (2)	0.051 (2)	0.0063 (16)	0.0102 (15)	0.0232 (17)
C6A	0.047 (2)	0.047 (2)	0.0412 (19)	0.0105 (16)	0.0120 (15)	0.0113 (15)
N1B	0.0341 (13)	0.0519 (17)	0.0249 (12)	−0.0009 (12)	0.0115 (11)	0.0140 (11)
C2B	0.0391 (17)	0.050 (2)	0.0390 (17)	0.0056 (15)	0.0134 (14)	0.0193 (15)
C3B	0.0458 (19)	0.0421 (19)	0.0473 (19)	0.0106 (15)	0.0255 (16)	0.0165 (15)
O4B	0.0393 (12)	0.0470 (13)	0.0405 (12)	0.0065 (10)	0.0236 (10)	0.0182 (10)
C5B	0.0435 (18)	0.051 (2)	0.0327 (16)	0.0116 (16)	0.0187 (14)	0.0165 (14)
C6B	0.0446 (18)	0.050 (2)	0.0323 (16)	0.0067 (15)	0.0197 (14)	0.0111 (14)
N1C	0.0434 (15)	0.072 (2)	0.0432 (15)	0.0116 (14)	0.0223 (12)	0.0235 (14)
O1C	0.0434 (15)	0.072 (2)	0.0432 (15)	0.0116 (14)	0.0223 (12)	0.0235 (14)
C2C	0.053 (2)	0.062 (3)	0.052 (2)	0.0099 (19)	0.0241 (18)	0.023 (2)
C3C	0.047 (2)	0.070 (3)	0.052 (2)	0.0154 (19)	0.0216 (18)	0.0289 (19)

Geometric parameters (Å, º)

O1—C1	1.357 (3)	C5A—C6A	1.505 (5)
O1—H11	1.02 (5)	C5A—H5A1	0.9700
C1—C2	1.386 (4)	C5A—H5A2	0.9700
C1—C6	1.394 (4)	C6A—H6A2	0.9700
C2—C3	1.377 (4)	C6A—H6A1	0.9700
C2—H2	0.9300	N1B—C6B	1.464 (4)
C3—C4	1.398 (4)	N1B—C2B	1.470 (4)
C3—H3	0.9300	N1B—H1B1	0.895 (10)
C4—C5	1.390 (4)	C2B—C3B	1.509 (4)
C4—N1	1.418 (4)	C2B—H2B1	0.9700
C5—C6	1.388 (4)	C2B—H2B2	0.9700
C5—H5	0.9300	C3B—O4B	1.429 (4)
C6—H6	0.9300	C3B—H3B2	0.9700
N1—C7	1.354 (4)	C3B—H3B1	0.9700
N1—H1	0.97 (4)	O4B—C5B	1.421 (4)
C7—O2	1.228 (4)	C5B—C6B	1.513 (4)
C7—C8	1.505 (4)	C5B—H5B1	0.9700
C8—H8A	0.9600	C5B—H5B2	0.9700
C8—H8B	0.9600	C6B—H6B2	0.9700
C8—H8C	0.9600	C6B—H6B1	0.9700
N1A—C6A	1.465 (4)	N1C—C2C	1.444 (5)
N1A—C2A	1.471 (4)	N1C—C3C^i	1.450 (4)
N1A—H1A1	0.892 (10)	N1C—H1C1	0.903 (10)
C2A—C3A	1.512 (5)	C2C—C3C	1.497 (5)
C2A—H2A1	0.9700	C2C—H2C2	1.09 (5)
C2A—H2A2	0.9700	C2C—H2C1	0.97 (4)
C3A—O4A	1.424 (4)	C3C—O1C^i	1.450 (4)
C3A—H3A2	0.9700	C3C—N1C^i	1.450 (4)
C3A—H3A1	0.9700	C3C—H3CA	1.12 (4)
O4A—C5A	1.436 (4)	C3C—H3CB	1.11 (4)
C1—O1—H11	112 (3)	N1A—C6A—C5A	113.3 (3)
O1—C1—C2	117.9 (2)	N1A—C6A—H6A2	108.9
O1—C1—C6	123.0 (3)	C5A—C6A—H6A2	108.9
C2—C1—C6	119.1 (3)	N1A—C6A—H6A1	108.9
C3—C2—C1	120.4 (3)	C5A—C6A—H6A1	108.9
C3—C2—H2	119.8	H6A2—C6A—H6A1	107.7
C1—C2—H2	119.8	C6B—N1B—C2B	109.4 (3)
C2—C3—C4	121.3 (3)	C6B—N1B—H1B1	111 (3)
C2—C3—H3	119.3	C2B—N1B—H1B1	106 (3)
C4—C3—H3	119.3	N1B—C2B—C3B	108.6 (3)
C5—C4—C3	118.1 (3)	N1B—C2B—H2B1	110.0
C5—C4—N1	125.1 (3)	C3B—C2B—H2B1	110.0
C3—C4—N1	116.8 (3)	N1B—C2B—H2B2	110.0
C6—C5—C4	120.8 (3)	C3B—C2B—H2B2	110.0
C6—C5—H5	119.6	H2B1—C2B—H2B2	108.3
C4—C5—H5	119.6	O4B—C3B—C2B	111.3 (3)
C5—C6—C1	120.4 (3)	O4B—C3B—H3B2	109.4
C5—C6—H6	119.8	C2B—C3B—H3B2	109.4
C1—C6—H6	119.8	O4B—C3B—H3B1	109.4
C7—N1—C4	127.8 (3)	C2B—C3B—H3B1	109.4
C7—N1—H1	118 (2)	H3B2—C3B—H3B1	108.0
C4—N1—H1	114 (2)	C5B—O4B—C3B	111.1 (2)
O2—C7—N1	123.2 (3)	O4B—C5B—C6B	111.6 (3)
O2—C7—C8	121.7 (3)	O4B—C5B—H5B1	109.3
N1—C7—C8	115.1 (3)	C6B—C5B—H5B1	109.3
C7—C8—H8A	109.5	O4B—C5B—H5B2	109.3
C7—C8—H8B	109.5	C6B—C5B—H5B2	109.3
H8A—C8—H8B	109.5	H5B1—C5B—H5B2	108.0
C7—C8—H8C	109.5	N1B—C6B—C5B	108.9 (3)
H8A—C8—H8C	109.5	N1B—C6B—H6B2	109.9
H8B—C8—H8C	109.5	C5B—C6B—H6B2	109.9
C6A—N1A—C2A	109.5 (3)	N1B—C6B—H6B1	109.9
C6A—N1A—H1A1	115 (3)	C5B—C6B—H6B1	109.9
C2A—N1A—H1A1	99 (3)	H6B2—C6B—H6B1	108.3
N1A—C2A—C3A	113.2 (3)	C2C—N1C—C3C^i	110.3 (3)
N1A—C2A—H2A1	108.9	C2C—N1C—H1C1	104 (6)
C3A—C2A—H2A1	108.9	C3C^i—N1C—H1C1	104 (6)
N1A—C2A—H2A2	108.9	N1C—C2C—C3C	112.5 (4)
C3A—C2A—H2A2	108.9	N1C—C2C—H2C2	113 (2)
H2A1—C2A—H2A2	107.8	C3C—C2C—H2C2	98 (2)
O4A—C3A—C2A	110.8 (3)	N1C—C2C—H2C1	109 (2)
O4A—C3A—H3A2	109.5	C3C—C2C—H2C1	110 (2)
C2A—C3A—H3A2	109.5	H2C2—C2C—H2C1	114 (3)
O4A—C3A—H3A1	109.5	O1C^i—C3C—N1C^i	0.0 (2)
C2A—C3A—H3A1	109.5	O1C^i—C3C—C2C	111.8 (3)
H3A2—C3A—H3A1	108.1	N1C^i—C3C—C2C	111.8 (3)
C3A—O4A—C5A	111.2 (3)	O1C^i—C3C—H3CA	113 (2)
O4A—C5A—C6A	110.7 (3)	N1C^i—C3C—H3CA	113 (2)
O4A—C5A—H5A1	109.5	C2C—C3C—H3CA	105 (2)
C6A—C5A—H5A1	109.5	O1C^i—C3C—H3CB	108.3 (19)
O4A—C5A—H5A2	109.5	N1C^i—C3C—H3CB	108.3 (19)
C6A—C5A—H5A2	109.5	C2C—C3C—H3CB	108 (2)
H5A1—C5A—H5A2	108.1	H3CA—C3C—H3CB	111 (3)

Symmetry code: (i) −x+3, −y+3, −z.