2-[(1S,3S)-3-Acetyl-2,2-dimethyl­cyclo­butyl]-N-(2,6-difluoro­phen­yl)acetamide

Yin, Y.; Han, C.; Song, Z.; Wang, Z.

doi:10.1107/S1600536807043127

2-[(1S,3S)-3-Acetyl-2,2-dimethylcyclobutyl]-N-(2,6-difluorophenyl)acetamide

The title compound, C₁₆H₁₉F₂NO₂, was synthesized from 2,6-difluorobenzenamine and 2-(3-acetyl-2,2-dimethylcyclobutyl)acetyl chloride, which was obtained through the reaction of 2-(3-acetyl-2,2-dimethylcyclobutyl)acetic acid (pinonic acid) and thionyl chloride. The crystal structure involves N—H

O hydrogen bonds.

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Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807043127/at2381sup1.cif Contains datablocks I, global
	Structure factor file (CIF format) https://doi.org/10.1107/S1600536807043127/at2381Isup2.hkl Contains datablock I

CCDC reference: 656006

checkCIF report

Key indicators

Single-crystal X-ray study
T = 293 K
Mean (C-C) = 0.006 Å
R factor = 0.069
wR factor = 0.207
Data-to-parameter ratio = 15.9

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT062_ALERT_4_C Rescale T(min) & T(max) by .....................       1.03
PLAT152_ALERT_1_C Supplied and Calc Volume s.u. Inconsistent .....          ?
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for         C2
PLAT340_ALERT_3_C Low Bond Precision on C-C Bonds (x 1000) Ang ...          6
PLAT720_ALERT_4_C Number of Unusual/Non-Standard Label(s) ........          1

Alert level G
PLAT199_ALERT_1_G Check the Reported _cell_measurement_temperature        293 K
PLAT200_ALERT_1_G Check the Reported _diffrn_ambient_temperature .        293 K
PLAT793_ALERT_1_G Check the Absolute Configuration of C3     = ...          S
PLAT793_ALERT_1_G Check the Absolute Configuration of C5     = ...          S

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   5 ALERT level C = Check and explain
   4 ALERT level G = General alerts; check

   5 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
   1 ALERT type 3 Indicator that the structure quality may be low
   2 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

Comment top

The cyclobutane moiety is a structural feature present in several natural or designed products with interesting biological properties (Moglioni et al., 2000). Some researchers have synthesized many bioactive substances, such as sex pheromones (Wolk et al., 1986), juvenile hormones (Ribas et al., 1980) etc. Thus, using pinonic acid as a starting material, we may synthesize new cyclobutane derivatives with biological properties. We have synthesized the title compound and report here its crystal structure.

The molecular structure is shown in Fig. 1 and the crystal packing in Fig. 2.

Related literature top

For related literature, see: Moglioni et al. (2000); Ribas et al. (1980); Wolk & Goldschmidt (1986).

Experimental top

The title compound was synthesized from 2,6-difluorobenzenamine and 2-(3-acetyl-2,2-dimethylcyclobutyl) acetyl chloride at room temperature.The acetyl chloride was obtained using -(3-acetyl-2,2-dimethylcyclobutyl)acetic acid (pinonic acid),thionyl chloride as raw materials and dichloromethane as solvent. Pinonic acid(27 mmol) and thionyl chloride(32 mmol) were dissolved in dichloromethane(50 ml). The resulting mixture was refluxed for 8 h. After refluxing the solvent was distilled away under vacuum and the remainder was 2-(3-acetyl-2,2-dimethylcyclobutyl)acetyl chloride. The acetyl chloride reacted with 2,6-difluorobenzenamine(27 mmol) for 24 h using dichloromethane as solvent. After the reaction was complete the solvent was distilled away and the crude title compound was gained. The pure compound was obtained by crystallizing from a mixture of ethanol (40 ml) and water (40 ml). Crystals of the title compound suitable for X-ray diffraction were obtained by slow evaporation of an ethanol solution.

Structure description top

The molecular structure is shown in Fig. 1 and the crystal packing in Fig. 2.

For related literature, see: Moglioni et al. (2000); Ribas et al. (1980); Wolk & Goldschmidt (1986).

Computing details top

Data collection: CAD-4 Software (Enraf–Nonius, 1989); cell refinement: CAD-4 Software (Enraf–Nonius, 1989); data reduction: XCAD4 (Harms & Wocadlo, 1995); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Siemens, 1996); software used to prepare material for publication: SHELXS97 (Sheldrick, 1997).

Figures top

Fig. 1. A view of the molecular structure of (I), showing displacement ellipsoids at the 30% probability level. Dash lines indicate N—H···O hydrogen bonds and O—H···N hydrogen bonds.

2-[(1S,3S)-3-acetyl-2,2-dimethylcyclobutyl]-N-(2,6-difluorophenyl)acetamide top

Crystal data top

C₁₆H₁₉F₂NO₂	F(000) = 624
M_r = 295.32	D_x = 1.274 Mg m⁻³
Monoclinic, P2₁/n	Melting point: 392 K
Hall symbol: -P 2yn	Mo Kα radiation, λ = 0.71073 Å
a = 8.7840 (18) Å	Cell parameters from 25 reflections
b = 12.914 (3) Å	θ = 9–14°
c = 13.747 (3) Å	µ = 0.10 mm⁻¹
β = 99.20 (3)°	T = 293 K
V = 1539.4 (5) Å³	Block, colourless
Z = 4	0.40 × 0.20 × 0.10 mm

Data collection top

Nonius CAD4 diffractometer	1682 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.032
Graphite monochromator	θ_max = 26.0°, θ_min = 2.2°
ω/2θ scans	h = −10→10
Absorption correction: ψ scan (North et al., 1968)	k = 0→15
T_min = 0.931, T_max = 0.960	l = 0→16
3222 measured reflections	3 standard reflections every 200 reflections
3022 independent reflections	intensity decay: none

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.069	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.207	H-atom parameters constrained
S = 1.01	w = 1/[σ²(F_o²) + (0.060P)² + 2.3P] where P = (F_o² + 2F_c²)/3
3022 reflections	(Δ/σ)_max < 0.001
190 parameters	Δρ_max = 0.25 e Å⁻³
0 restraints	Δρ_min = −0.26 e Å⁻³

Crystal data top

C₁₆H₁₉F₂NO₂	V = 1539.4 (5) Å³
M_r = 295.32	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 8.7840 (18) Å	µ = 0.10 mm⁻¹
b = 12.914 (3) Å	T = 293 K
c = 13.747 (3) Å	0.40 × 0.20 × 0.10 mm
β = 99.20 (3)°

Data collection top

Nonius CAD4 diffractometer	1682 reflections with I > 2σ(I)
Absorption correction: ψ scan (North et al., 1968)	R_int = 0.032
T_min = 0.931, T_max = 0.960	3 standard reflections every 200 reflections
3222 measured reflections	intensity decay: none
3022 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.069	0 restraints
wR(F²) = 0.207	H-atom parameters constrained
S = 1.01	Δρ_max = 0.25 e Å⁻³
3022 reflections	Δρ_min = −0.26 e Å⁻³
190 parameters

Special details top

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. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	U_iso*/U_eq
F1	0.3196 (4)	0.6850 (2)	1.17341 (19)	0.0972 (10)
F2	0.1731 (4)	0.97005 (19)	0.9730 (2)	0.0912 (9)
O1	0.4326 (4)	0.3369 (3)	1.0109 (3)	0.0866 (10)
O2	0.0165 (3)	0.7648 (2)	0.9196 (2)	0.0720 (8)
N	0.2668 (4)	0.7654 (2)	0.9872 (2)	0.0567 (8)
H0A	0.3592	0.7486	0.9802	0.068*
C1	0.2701 (7)	0.2067 (3)	0.9316 (4)	0.0961 (17)
H1A	0.3562	0.1623	0.9541	0.144*
H1B	0.2472	0.2041	0.8609	0.144*
H1C	0.1819	0.1838	0.9589	0.144*
C2	0.3089 (6)	0.3152 (3)	0.9638 (3)	0.0621 (11)
C3	0.1890 (5)	0.3958 (3)	0.9335 (3)	0.0561 (10)
H3A	0.0876	0.3686	0.9416	0.067*
C4	0.1781 (4)	0.4476 (3)	0.8287 (3)	0.0551 (9)
C5	0.1363 (5)	0.5490 (3)	0.8790 (3)	0.0538 (9)
H5A	0.0242	0.5511	0.8766	0.065*
C6	0.2092 (5)	0.5046 (3)	0.9783 (3)	0.0552 (10)
H6A	0.1494	0.5167	1.0307	0.066*
H6B	0.3160	0.5247	0.9984	0.066*
C7	0.0567 (6)	0.4049 (4)	0.7473 (4)	0.0863 (15)
H7A	−0.0410	0.4021	0.7700	0.129*
H7B	0.0859	0.3366	0.7299	0.129*
H7C	0.0487	0.4492	0.6906	0.129*
C8	0.3368 (5)	0.4528 (3)	0.7956 (3)	0.0697 (12)
H8A	0.3563	0.3889	0.7640	0.105*
H8B	0.4150	0.4637	0.8519	0.105*
H8C	0.3382	0.5090	0.7500	0.105*
C9	0.1893 (5)	0.6545 (3)	0.8476 (3)	0.0604 (10)
H9A	0.2997	0.6538	0.8474	0.072*
H9B	0.1379	0.6710	0.7816	0.072*
C10	0.1500 (5)	0.7342 (3)	0.9197 (3)	0.0521 (9)
C11	0.2446 (4)	0.8255 (3)	1.0702 (3)	0.0518 (9)
C12	0.1926 (5)	0.9262 (3)	1.0629 (3)	0.0602 (10)
C13	0.1628 (5)	0.9823 (3)	1.1429 (4)	0.0743 (13)
H13A	0.1261	1.0498	1.1354	0.089*
C14	0.1885 (5)	0.9364 (4)	1.2332 (4)	0.0809 (14)
H14A	0.1694	0.9735	1.2880	0.097*
C15	0.2414 (6)	0.8377 (4)	1.2453 (3)	0.0798 (14)
H15A	0.2602	0.8076	1.3075	0.096*
C16	0.2665 (5)	0.7839 (3)	1.1642 (3)	0.0661 (11)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.157 (3)	0.0625 (17)	0.0727 (17)	0.0316 (17)	0.0194 (17)	0.0134 (13)
F2	0.141 (2)	0.0525 (15)	0.0784 (18)	0.0138 (15)	0.0126 (16)	0.0088 (13)
O1	0.084 (2)	0.076 (2)	0.101 (3)	0.0196 (19)	0.018 (2)	0.0029 (19)
O2	0.0753 (19)	0.070 (2)	0.0693 (19)	0.0084 (16)	0.0069 (15)	−0.0178 (15)
N	0.067 (2)	0.0504 (19)	0.0536 (19)	0.0059 (16)	0.0134 (16)	−0.0069 (15)
C1	0.139 (5)	0.044 (3)	0.113 (4)	0.009 (3)	0.048 (4)	−0.006 (3)
C2	0.080 (3)	0.047 (2)	0.068 (3)	0.005 (2)	0.037 (2)	0.008 (2)
C3	0.070 (2)	0.0351 (19)	0.070 (3)	−0.0024 (17)	0.033 (2)	0.0002 (18)
C4	0.064 (2)	0.049 (2)	0.056 (2)	0.0020 (18)	0.0200 (18)	−0.0100 (18)
C5	0.073 (2)	0.043 (2)	0.050 (2)	0.0064 (18)	0.0218 (18)	−0.0021 (17)
C6	0.080 (3)	0.046 (2)	0.046 (2)	0.0025 (19)	0.0292 (19)	−0.0013 (17)
C7	0.090 (3)	0.079 (3)	0.083 (3)	0.008 (3)	−0.008 (3)	−0.027 (3)
C8	0.099 (3)	0.058 (3)	0.061 (3)	0.011 (2)	0.042 (2)	−0.003 (2)
C9	0.089 (3)	0.051 (2)	0.045 (2)	0.003 (2)	0.019 (2)	−0.0009 (18)
C10	0.071 (2)	0.040 (2)	0.049 (2)	0.0011 (19)	0.0207 (19)	0.0050 (17)
C11	0.062 (2)	0.042 (2)	0.052 (2)	0.0051 (17)	0.0099 (17)	−0.0065 (17)
C12	0.071 (3)	0.051 (2)	0.057 (2)	0.0063 (19)	0.005 (2)	−0.003 (2)
C13	0.078 (3)	0.058 (3)	0.084 (3)	0.015 (2)	0.004 (2)	−0.023 (2)
C14	0.086 (3)	0.088 (4)	0.066 (3)	0.017 (3)	0.005 (2)	−0.028 (3)
C15	0.096 (3)	0.092 (4)	0.050 (2)	0.008 (3)	0.009 (2)	−0.011 (3)
C16	0.090 (3)	0.051 (2)	0.059 (3)	0.009 (2)	0.016 (2)	0.002 (2)

Geometric parameters (Å, º) top

F1—C16	1.359 (5)	C6—H6A	0.9700
F2—C12	1.345 (5)	C6—H6B	0.9700
O1—C2	1.206 (5)	C7—H7A	0.9600
O2—C10	1.237 (4)	C7—H7B	0.9600
N—C10	1.332 (5)	C7—H7C	0.9600
N—C11	1.419 (4)	C8—H8A	0.9600
N—H0A	0.8600	C8—H8B	0.9600
C1—C2	1.492 (6)	C8—H8C	0.9600
C1—H1A	0.9600	C9—C10	1.507 (5)
C1—H1B	0.9600	C9—H9A	0.9700
C1—H1C	0.9600	C9—H9B	0.9700
C2—C3	1.492 (6)	C11—C12	1.376 (5)
C3—C6	1.533 (5)	C11—C16	1.383 (5)
C3—C4	1.577 (5)	C12—C13	1.377 (6)
C3—H3A	0.9800	C13—C14	1.363 (6)
C4—C7	1.520 (6)	C13—H13A	0.9300
C4—C8	1.536 (5)	C14—C15	1.357 (7)
C4—C5	1.551 (5)	C14—H14A	0.9300
C5—C6	1.524 (5)	C15—C16	1.361 (6)
C5—C9	1.525 (5)	C15—H15A	0.9300
C5—H5A	0.9800

C10—N—C11	122.4 (3)	H7A—C7—H7B	109.5
C10—N—H0A	118.8	C4—C7—H7C	109.5
C11—N—H0A	118.8	H7A—C7—H7C	109.5
C2—C1—H1A	109.5	H7B—C7—H7C	109.5
C2—C1—H1B	109.5	C4—C8—H8A	109.5
H1A—C1—H1B	109.5	C4—C8—H8B	109.5
C2—C1—H1C	109.5	H8A—C8—H8B	109.5
H1A—C1—H1C	109.5	C4—C8—H8C	109.5
H1B—C1—H1C	109.5	H8A—C8—H8C	109.5
O1—C2—C1	121.5 (4)	H8B—C8—H8C	109.5
O1—C2—C3	121.5 (4)	C10—C9—C5	108.2 (3)
C1—C2—C3	117.0 (4)	C10—C9—H9A	110.1
C2—C3—C6	119.7 (4)	C5—C9—H9A	110.1
C2—C3—C4	119.2 (3)	C10—C9—H9B	110.1
C6—C3—C4	87.9 (3)	C5—C9—H9B	110.1
C2—C3—H3A	109.4	H9A—C9—H9B	108.4
C6—C3—H3A	109.4	O2—C10—N	121.9 (3)
C4—C3—H3A	109.4	O2—C10—C9	122.3 (4)
C7—C4—C8	111.1 (3)	N—C10—C9	115.7 (4)
C7—C4—C5	116.5 (3)	C12—C11—C16	115.5 (4)
C8—C4—C5	112.7 (3)	C12—C11—N	122.9 (4)
C7—C4—C3	116.8 (4)	C16—C11—N	121.5 (3)
C8—C4—C3	111.4 (3)	F2—C12—C11	117.3 (4)
C5—C4—C3	86.3 (3)	F2—C12—C13	120.0 (4)
C6—C5—C9	119.1 (3)	C11—C12—C13	122.8 (4)
C6—C5—C4	89.2 (3)	C14—C13—C12	118.3 (4)
C9—C5—C4	121.6 (3)	C14—C13—H13A	120.8
C6—C5—H5A	108.5	C12—C13—H13A	120.8
C9—C5—H5A	108.5	C15—C14—C13	121.5 (4)
C4—C5—H5A	108.5	C15—C14—H14A	119.2
C5—C6—C3	88.8 (3)	C13—C14—H14A	119.2
C5—C6—H6A	113.8	C14—C15—C16	118.5 (5)
C3—C6—H6A	113.8	C14—C15—H15A	120.8
C5—C6—H6B	113.8	C16—C15—H15A	120.8
C3—C6—H6B	113.8	F1—C16—C15	120.1 (4)
H6A—C6—H6B	111.1	F1—C16—C11	116.6 (4)
C4—C7—H7A	109.5	C15—C16—C11	123.3 (4)
C4—C7—H7B	109.5

O1—C2—C3—C6	−11.5 (6)	C4—C5—C9—C10	−171.9 (3)
C1—C2—C3—C6	169.5 (4)	C11—N—C10—O2	7.8 (6)
O1—C2—C3—C4	94.2 (5)	C11—N—C10—C9	−168.6 (3)
C1—C2—C3—C4	−84.7 (5)	C5—C9—C10—O2	−74.6 (5)
C2—C3—C4—C7	98.3 (5)	C5—C9—C10—N	101.8 (4)
C6—C3—C4—C7	−138.4 (4)	C10—N—C11—C12	−67.9 (5)
C2—C3—C4—C8	−30.8 (5)	C10—N—C11—C16	108.6 (4)
C6—C3—C4—C8	92.5 (3)	C16—C11—C12—F2	178.6 (4)
C2—C3—C4—C5	−143.8 (4)	N—C11—C12—F2	−4.7 (6)
C6—C3—C4—C5	−20.5 (3)	C16—C11—C12—C13	−0.5 (6)
C7—C4—C5—C6	138.9 (4)	N—C11—C12—C13	176.2 (4)
C8—C4—C5—C6	−91.0 (4)	F2—C12—C13—C14	−178.0 (4)
C3—C4—C5—C6	20.6 (3)	C11—C12—C13—C14	1.1 (7)
C7—C4—C5—C9	−97.0 (5)	C12—C13—C14—C15	−0.3 (8)
C8—C4—C5—C9	33.2 (5)	C13—C14—C15—C16	−1.1 (8)
C3—C4—C5—C9	144.8 (4)	C14—C15—C16—F1	179.9 (4)
C9—C5—C6—C3	−147.4 (3)	C14—C15—C16—C11	1.7 (8)
C4—C5—C6—C3	−21.2 (3)	C12—C11—C16—F1	−179.2 (4)
C2—C3—C6—C5	143.6 (3)	N—C11—C16—F1	4.0 (6)
C4—C3—C6—C5	20.9 (3)	C12—C11—C16—C15	−1.0 (7)
C6—C5—C9—C10	−63.1 (5)	N—C11—C16—C15	−177.7 (4)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N—H0A···O1ⁱ	0.86	2.12	2.949 (5)	161

Symmetry code: (i) −x+1, −y+1, −z+2.

Experimental details

Crystal data
Chemical formula	C₁₆H₁₉F₂NO₂
M_r	295.32
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	293
a, b, c (Å)	8.7840 (18), 12.914 (3), 13.747 (3)
β (°)	99.20 (3)
V (Å³)	1539.4 (5)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.10
Crystal size (mm)	0.40 × 0.20 × 0.10

Data collection
Diffractometer	Nonius CAD4
Absorption correction	ψ scan (North et al., 1968)
T_min, T_max	0.931, 0.960
No. of measured, independent and observed [I > 2σ(I)] reflections	3222, 3022, 1682
R_int	0.032
(sin θ/λ)_max (Å⁻¹)	0.616

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.069, 0.207, 1.01
No. of reflections	3022
No. of parameters	190
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.25, −0.26

Computer programs: CAD-4 Software (Enraf–Nonius, 1989), XCAD4 (Harms & Wocadlo, 1995), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), SHELXTL (Siemens, 1996).