1-Methoxy­methyl-5-ethyl-6-(1-naphthyl­methyl)­uracil

The title compound, C₁₉H₂₀N₂O₃ is composed of two moieties, the pyrimidinyl plane and the naphthyl aromatic plane; the dihedral angle betwen them is 90.9 (3)°. A centrosymmetric dimer is formed in the crystal through pairs of N—H...O hydrogen bonds.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.004 Å
• R factor = 0.060
• wR factor = 0.138
• Data-to-parameter ratio = 12.1

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry

---

S1. Comment

Acquired immunodeficiency syndrome (AIDS) is caused by human immunodeficiency virus (HIV), an RNA-dependent retrovirus (Barre-Sinoussi et al., 1983; Gallo et al., 1983). The reverse transcriptase (RT) is crucial for the whole life circle of HIV, and is a special target for designing selective HIV-1 reverse transcriptase inhibitors (RTIs; Spence et al., 1995; Cox & Scinclair, 2000). The synthesis of HIV-RT inhibitors, which may have a better combination with the active binding pocket, becomes a major challenge facing the modern medicinal chemistry (Hopkins et al., 1999). In this case, the title compound, (I), was synthesized for the first time as a potential HIV-RT inhibitor (De Clercq et al., 1991; Pedersen & Pedersen, 2000).

The structure of (I) consists of two aromatic planes, one is the pyrimidinyl and the other the naphthyl moiety (Fig. 1). This kind of butterfly configuration of HEPT analogs has been proposed by Arnold et al. (1996) and was verified by our work. The dimer of the title molecule is formed by the cyclic N3—H3···O2ⁱ hydrogen bond. The dimers are further linked by C—H···O interactions (Table 1 and Fig. 2). The distance between the two naphthyl planes related by an inversion center is about 3.5 Å, from which it can be deduced that a π–π stack effect might exist between the naphthyl planes in the whole lattice. On the other hand, π–π stack does not exist between the two pyrimidinyl planes.

The X-ray results may be compared with the data achieved by MM2 calculations (Leach, 1996; Pople et al., 1967). While agreement between most of the calculated and measured parameters is good, the C7—O3 bond length of 1 N-side chain is a little less than the value calculated by MM2 method, this implies that C—O is somewhat like a double bond, which could be accounted for by the conjunction effect between the lone-pair electron on oxygen and the pyrimidinyl ring.

S2. Experimental

To 5-ethyl-6-(1-naphthylmethyl)uracils (7 g, 25 mmol) suspended in CH₂Cl₂ (30 ml) was added N, O-bis(trimethylsilyl)acetamide (13.6 ml, 55 mmol) under a nitrogen atmosphere, and the mixture was stirred at room temperature for 3 h. When the silylation was completed, tetrabutyl ammonium iodide (93 mg, 0.25 mmol) and chloromethyl methyl ether (2.8 ml, 30.0 mmol) were added to the above solution. After this, the mixture was heated to refluxed for 3 h and allowed to cool to room temperature. When the reaction was finished (TLC analysis), the reaction mixture was poured into cold saturated NaHCO₃ solution (10 ml), EtOH (5 ml), and stirred for an additional 2 h. The organic phase was washed with brine (15 ml), dried over anhydrous MgSO₄ and concentrated to dryness. Column chromatography gave white foam, which was recrystallized with ethyl acetate to give the title compound as colourless block crystals suitable for X-Ray diffraction (3.02 g, 9.3 mmol, 37.2%). The product was characterized by IR, mass spectrometry (EI—HR), ¹H NMR, ¹³C NMR and ¹H-¹H NOESY.

S3. Refinement

All H atoms were refined isotropically. The C—H and N—H bond lengths are 0.89 (4)–1.03 (6) Å and 0.91 (2) Å, respectively.

Computing details

Data collection: SMART (Bruker, 1997); cell refinement: SMART; data reduction: SAINT (Bruker, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997).

Figures

	Fig. 1. The molecular structure of (I), showing 30% probability displacement ellipsoids.
	Fig. 2. Packing diagram for (I), viewed down the c axis.

1-methoxymethyl-5-ethyl-6-(1-naphthyl)uracil

Crystal data

C19H20N2O3	Dx = 1.333 Mg m^−3
Mr = 324.14	Melting point = 169–170. K
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
a = 10.325 (4) Å	Cell parameters from 783 reflections
b = 14.813 (5) Å	θ = 2.4–26.6°
c = 11.295 (4) Å	µ = 0.09 mm^−1
β = 110.709 (5)°	T = 293 K
V = 1616.0 (10) Å^3	Block, colourless
Z = 4	0.25 × 0.20 × 0.15 mm
F(000) = 688

Data collection

CCD area-detector diffractometer	3583 independent reflections
Radiation source: fine-focus sealed tube	2193 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.040
ω scans	θmax = 27.2°, θmin = 2.3°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −12→13
Tmin = 0.978, Tmax = 0.987	k = −19→14
7908 measured reflections	l = −14→13

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.060	Hydrogen site location: difference Fourier map
wR(F^2) = 0.138	All H-atom parameters refined
S = 1.01	w = 1/[σ^2(Fo^2) + (0.0557P)^2 + 0.2622P] where P = (Fo^2 + 2Fc^2)/3
3583 reflections	(Δ/σ)max < 0.001
297 parameters	Δρmax = 0.20 e Å^−3
0 restraints	Δρmin = −0.13 e Å^−3

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. 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 (Ų)

	x	y	z	Uiso*/Ueq
N1	0.52974 (18)	0.28010 (12)	0.06113 (17)	0.0423 (5)
C2	0.4926 (2)	0.21426 (15)	−0.0330 (2)	0.0430 (5)
O1	0.44760 (19)	0.23081 (11)	−0.14499 (16)	0.0618 (5)
N3	0.5093 (2)	0.12774 (13)	0.01138 (18)	0.0442 (5)
C4	0.5643 (2)	0.10093 (15)	0.1344 (2)	0.0397 (5)
O2	0.57884 (16)	0.01964 (10)	0.15965 (14)	0.0506 (4)
C5	0.6004 (2)	0.17152 (14)	0.2284 (2)	0.0388 (5)
C6	0.5789 (2)	0.25853 (14)	0.1896 (2)	0.0398 (5)
C7	0.5221 (3)	0.37493 (16)	0.0181 (3)	0.0509 (6)
O3	0.65089 (19)	0.41605 (11)	0.05445 (17)	0.0643 (5)
C8	0.7382 (5)	0.3807 (3)	−0.0063 (5)	0.0883 (11)
C9	0.6572 (3)	0.1406 (2)	0.3644 (2)	0.0550 (7)
C10	0.5471 (4)	0.1140 (3)	0.4181 (3)	0.0688 (8)
C11	0.6010 (3)	0.33726 (17)	0.2780 (2)	0.0463 (6)
C12	0.4681 (2)	0.37694 (14)	0.28414 (19)	0.0415 (5)
C13	0.3547 (2)	0.32459 (18)	0.2662 (2)	0.0492 (6)
C14	0.2350 (3)	0.35759 (19)	0.2819 (2)	0.0564 (7)
C15	0.2296 (3)	0.44494 (19)	0.3155 (2)	0.0565 (7)
C16	0.3428 (3)	0.50320 (16)	0.3335 (2)	0.0468 (6)
C17	0.3389 (4)	0.59437 (19)	0.3686 (2)	0.0643 (8)
C18	0.4476 (4)	0.6499 (2)	0.3848 (3)	0.0691 (9)
C19	0.5653 (4)	0.61849 (17)	0.3666 (2)	0.0629 (7)
C20	0.5745 (3)	0.53011 (16)	0.3342 (2)	0.0522 (6)
C21	0.4636 (2)	0.46985 (15)	0.31698 (19)	0.0422 (5)
H3	0.478 (2)	0.0853 (16)	−0.050 (2)	0.053 (7)*
H7A	0.470 (3)	0.4085 (17)	0.056 (2)	0.059 (7)*
H7B	0.474 (2)	0.3715 (15)	−0.076 (2)	0.050 (6)*
H8A	0.816 (5)	0.412 (3)	0.018 (4)	0.133 (16)*
H8B	0.758 (4)	0.319 (3)	0.015 (3)	0.122 (14)*
H8C	0.683 (6)	0.377 (3)	−0.102 (6)	0.20 (2)*
H9A	0.712 (2)	0.1837 (16)	0.416 (2)	0.051 (7)*
H9B	0.712 (3)	0.0898 (18)	0.364 (2)	0.062 (8)*
H10A	0.587 (3)	0.0936 (19)	0.501 (3)	0.077 (9)*
H10B	0.488 (3)	0.065 (2)	0.367 (3)	0.090 (10)*
H10C	0.486 (3)	0.167 (2)	0.417 (3)	0.102 (11)*
H11A	0.660 (2)	0.3172 (14)	0.359 (2)	0.041 (6)*
H11B	0.657 (2)	0.3792 (16)	0.256 (2)	0.053 (7)*
H13	0.356 (2)	0.2637 (17)	0.242 (2)	0.055 (7)*
H14	0.158 (3)	0.3173 (17)	0.273 (2)	0.060 (7)*
H15	0.146 (3)	0.4715 (16)	0.329 (2)	0.063 (7)*
H17	0.259 (3)	0.6172 (16)	0.387 (2)	0.057 (7)*
H18	0.441 (3)	0.710 (2)	0.407 (2)	0.068 (8)*
H19	0.649 (3)	0.6588 (18)	0.377 (2)	0.071 (8)*
H20	0.661 (3)	0.5085 (17)	0.321 (2)	0.068 (8)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0494 (11)	0.0294 (10)	0.0497 (11)	−0.0004 (8)	0.0195 (9)	−0.0030 (8)
C2	0.0474 (13)	0.0369 (13)	0.0491 (15)	−0.0028 (10)	0.0224 (11)	−0.0034 (11)
O1	0.0883 (13)	0.0476 (11)	0.0477 (11)	0.0000 (9)	0.0219 (9)	−0.0001 (8)
N3	0.0597 (12)	0.0303 (10)	0.0456 (12)	−0.0018 (9)	0.0225 (9)	−0.0054 (9)
C4	0.0373 (12)	0.0343 (13)	0.0537 (14)	−0.0007 (10)	0.0238 (10)	−0.0034 (10)
O2	0.0648 (11)	0.0285 (9)	0.0593 (10)	0.0000 (8)	0.0232 (8)	0.0004 (7)
C5	0.0372 (11)	0.0333 (12)	0.0485 (13)	−0.0007 (10)	0.0185 (10)	−0.0032 (10)
C6	0.0371 (11)	0.0371 (13)	0.0487 (13)	−0.0016 (10)	0.0194 (10)	−0.0056 (10)
C7	0.0596 (16)	0.0297 (13)	0.0660 (18)	−0.0019 (12)	0.0254 (14)	−0.0013 (12)
O3	0.0706 (12)	0.0424 (10)	0.0877 (13)	−0.0127 (9)	0.0376 (10)	−0.0045 (9)
C8	0.087 (3)	0.074 (3)	0.129 (4)	−0.011 (2)	0.070 (3)	−0.005 (2)
C9	0.0591 (16)	0.0435 (15)	0.0532 (15)	−0.0065 (14)	0.0086 (13)	−0.0041 (12)
C10	0.082 (2)	0.073 (2)	0.0527 (18)	−0.0009 (19)	0.0252 (16)	0.0084 (17)
C11	0.0468 (14)	0.0393 (14)	0.0506 (15)	−0.0048 (12)	0.0143 (12)	−0.0109 (11)
C12	0.0502 (13)	0.0347 (12)	0.0419 (12)	0.0026 (10)	0.0191 (10)	−0.0036 (10)
C13	0.0515 (14)	0.0415 (14)	0.0577 (15)	−0.0009 (12)	0.0232 (12)	−0.0083 (12)
C14	0.0519 (16)	0.0603 (18)	0.0617 (16)	−0.0041 (14)	0.0258 (13)	−0.0036 (13)
C15	0.0531 (16)	0.0678 (19)	0.0540 (15)	0.0165 (14)	0.0254 (12)	0.0073 (13)
C16	0.0624 (15)	0.0436 (14)	0.0371 (12)	0.0140 (12)	0.0211 (11)	0.0039 (10)
C17	0.093 (2)	0.0508 (17)	0.0525 (16)	0.0265 (17)	0.0303 (15)	0.0062 (13)
C18	0.115 (3)	0.0331 (16)	0.0552 (17)	0.0113 (17)	0.0253 (16)	−0.0006 (12)
C19	0.089 (2)	0.0360 (15)	0.0572 (16)	−0.0052 (15)	0.0178 (15)	−0.0009 (12)
C20	0.0651 (17)	0.0402 (14)	0.0502 (14)	−0.0019 (13)	0.0191 (12)	−0.0014 (11)
C21	0.0560 (14)	0.0350 (12)	0.0347 (11)	0.0027 (11)	0.0151 (10)	0.0018 (9)

Geometric parameters (Å, º)

N1—C2	1.393 (3)	C10—H10B	0.99 (3)
N1—C6	1.395 (3)	C10—H10C	1.01 (4)
N1—C7	1.479 (3)	C11—C12	1.517 (3)
C2—O1	1.209 (3)	C11—H11A	0.95 (2)
C2—N3	1.365 (3)	C11—H11B	0.94 (2)
N3—C4	1.361 (3)	C12—C13	1.358 (3)
N3—H3	0.91 (2)	C12—C21	1.431 (3)
C4—O2	1.234 (2)	C13—C14	1.398 (3)
C4—C5	1.442 (3)	C13—H13	0.94 (2)
C5—C6	1.354 (3)	C14—C15	1.355 (4)
C5—C9	1.509 (3)	C14—H14	0.97 (3)
C6—C11	1.499 (3)	C15—C16	1.408 (4)
C7—O3	1.387 (3)	C15—H15	1.00 (3)
C7—H7A	0.94 (2)	C16—C17	1.412 (4)
C7—H7B	1.01 (2)	C16—C21	1.414 (3)
O3—C8	1.412 (4)	C17—C18	1.351 (4)
C8—H8A	0.89 (4)	C17—H17	0.98 (2)
C8—H8B	0.96 (4)	C18—C19	1.382 (4)
C8—H8C	1.03 (6)	C18—H18	0.93 (3)
C9—C10	1.517 (4)	C19—C20	1.371 (3)
C9—H9A	0.92 (2)	C19—H19	1.02 (3)
C9—H9B	0.94 (3)	C20—C21	1.410 (3)
C10—H10A	0.93 (3)	C20—H20	1.01 (3)
C2—N1—C6	122.31 (18)	C9—C10—H10C	110.4 (18)
C2—N1—C7	116.46 (19)	H10A—C10—H10C	109 (2)
C6—N1—C7	121.14 (19)	H10B—C10—H10C	108 (3)
O1—C2—N3	121.8 (2)	C6—C11—C12	113.86 (19)
O1—C2—N1	123.9 (2)	C6—C11—H11A	107.0 (13)
N3—C2—N1	114.4 (2)	C12—C11—H11A	111.0 (13)
C4—N3—C2	127.0 (2)	C6—C11—H11B	107.5 (14)
C4—N3—H3	119.3 (14)	C12—C11—H11B	114.0 (14)
C2—N3—H3	113.7 (14)	H11A—C11—H11B	102.6 (19)
O2—C4—N3	119.6 (2)	C13—C12—C21	118.8 (2)
O2—C4—C5	123.9 (2)	C13—C12—C11	121.2 (2)
N3—C4—C5	116.5 (2)	C21—C12—C11	119.9 (2)
C6—C5—C4	118.8 (2)	C12—C13—C14	122.4 (2)
C6—C5—C9	125.4 (2)	C12—C13—H13	119.3 (14)
C4—C5—C9	115.8 (2)	C14—C13—H13	118.3 (14)
C5—C6—N1	120.82 (19)	C15—C14—C13	119.7 (3)
C5—C6—C11	123.8 (2)	C15—C14—H14	120.4 (15)
N1—C6—C11	115.4 (2)	C13—C14—H14	119.9 (15)
O3—C7—N1	112.7 (2)	C14—C15—C16	120.8 (2)
O3—C7—H7A	105.8 (15)	C14—C15—H15	122.5 (14)
N1—C7—H7A	109.0 (15)	C16—C15—H15	116.7 (14)
O3—C7—H7B	113.7 (12)	C15—C16—C17	121.5 (2)
N1—C7—H7B	104.4 (13)	C15—C16—C21	119.5 (2)
H7A—C7—H7B	111 (2)	C17—C16—C21	119.0 (2)
C7—O3—C8	113.8 (3)	C18—C17—C16	121.0 (3)
O3—C8—H8A	108 (3)	C18—C17—H17	118.9 (14)
O3—C8—H8B	110 (2)	C16—C17—H17	119.9 (14)
H8A—C8—H8B	110 (4)	C17—C18—C19	120.5 (3)
O3—C8—H8C	109 (3)	C17—C18—H18	118.5 (16)
H8A—C8—H8C	117 (4)	C19—C18—H18	121.0 (16)
H8B—C8—H8C	102 (3)	C20—C19—C18	120.5 (3)
C5—C9—C10	114.2 (2)	C20—C19—H19	116.8 (15)
C5—C9—H9A	111.7 (14)	C18—C19—H19	122.7 (15)
C10—C9—H9A	108.0 (14)	C19—C20—C21	120.8 (3)
C5—C9—H9B	104.5 (15)	C19—C20—H20	119.4 (15)
C10—C9—H9B	109.6 (15)	C21—C20—H20	119.8 (15)
H9A—C9—H9B	109 (2)	C20—C21—C16	118.1 (2)
C9—C10—H10A	111.0 (17)	C20—C21—C12	123.1 (2)
C9—C10—H10B	110.8 (17)	C16—C21—C12	118.8 (2)
H10A—C10—H10B	108 (2)
N1—C7—O3—C8	67.9 (3)	C6—C11—C12—C13	30.6 (3)
C5—C6—C11—C12	−103.4 (3)	C6—C11—C12—C21	−153.3 (2)
N1—C6—C11—C12	74.8 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3···O2^i	0.91 (2)	1.94 (3)	2.843 (3)	170 (2)
C15—H15···O2^ii	1.00 (3)	2.48 (3)	3.476 (3)	171.7 (19)

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