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Acta Crystallogr Sect E Struct Rep Online. 2008 August 1; 64(Pt 8): o1491.
Published online 2008 July 16. doi:  10.1107/S1600536808021144
PMCID: PMC2962043

3-Ethyl­sulfanyl-5-methyl-1-phenyl-7-(pyrrolidin-1-yl)-1H-pyrimido[4,5-e][1,3,4]thia­diazine

Abstract

In the crystal structure of the title compound, C18H21N5S2, the thia­diazine six-membered ring and pyrrolidine five-membered ring display boat and envelope conformations, respectively. The crystal structure contains weak C—H(...)N and C—H(...)S hydrogen bonding.

Related literature

For general background, see: Rahimizadeh et al. (1997 [triangle]); Elliott (1981 [triangle]); Bakavoli et al. (2006 [triangle], 2007 [triangle], 2008 [triangle]).

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Object name is e-64-o1491-scheme1.jpg

Experimental

Crystal data

  • C18H21N5S2
  • M r = 371.52
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-64-o1491-efi1.jpg
  • a = 8.3601 (2) Å
  • b = 10.3596 (3) Å
  • c = 20.5754 (6) Å
  • V = 1781.98 (8) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.31 mm−1
  • T = 100 (2) K
  • 0.43 × 0.34 × 0.25 mm

Data collection

  • Bruker APEXII CCD area-detector diffractometer
  • Absorption correction: multi-scan (APEX2; Bruker, 2005 [triangle]) T min = 0.878, T max = 0.926
  • 36558 measured reflections
  • 6479 independent reflections
  • 5952 reflections with I > 2σ(I)
  • R int = 0.042

Refinement

  • R[F 2 > 2σ(F 2)] = 0.031
  • wR(F 2) = 0.076
  • S = 1.01
  • 6479 reflections
  • 228 parameters
  • H-atom parameters constrained
  • Δρmax = 0.39 e Å−3
  • Δρmin = −0.24 e Å−3
  • Absolute structure: Flack (1983 [triangle]), 2828 Friedel pairs
  • Flack parameter: −0.01 (4)

Data collection: APEX2 (Bruker, 2005 [triangle]); cell refinement: APEX2; data reduction: APEX2; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808021144/xu2431sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808021144/xu2431Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

The authors acknowledge Islamic Azad University, Ahvaz Branch, for financial support.

supplementary crystallographic information

Comment

The diverse biological activities of pyrimido [4,5-e][1,3,4]thiadiazine persuaded us to search for newer and more efficient synthetic methods for this class of heterocyclic compounds. These compounds have been described as being nucleoside analogues, anti-inflammatory, hypotensive, diuretic, and phosphodiesterase inhibitor agents. Despite their importance from pharmacological and synthetic point of views, comparatively few methods for their preparation have been reported. Pyrimido [4,5-e] [1,3,4]thiadiazines have been solely synthesized from pyrimidines. Previous routes to such systems have involved condensation of 2,4- dichloro–5-nitro -6-methylpyrimidine with dithizone (Rahimizadeh et al., 1997) via Smiles Rearrangement, heterocyclization of 6-hydrazino substituted uracils with isothiocyanates and N-bromosuccinimide, reaction of thiohydrazides with 4,5- dihalopyrimidines (Elliott, 1981), condensation of 5-bromo-2-chloro-6-methyl-4-(1-methylhydrazino) pyrimidine with carbondisulfide and alkylhalides (Bakavoli et al., 2007) and isothiocyanates (Bakavoli et al., 2008). In aprevious communication (Bakavoli et al., 2006), we described a new approach for the formation of 1-phenyl-1H-[1,3,4]thiadiazino[5,6-b]quinoxalines. The synthesis we developed involved heterocyclization of alkyl-2-phenylhydrazinecarbodithioates as bifunctional nucleophiles with 2,3-dichloroquinoxaline as an electrophile. To extend the scope of this strategy, we explored other electrophilic species that could successfully undergo similar reaction.

The molecular structure is shown in Fig. 1. In the title crystal structure, the thiadiazine six-membered ring and pyrrolidine five-membered ring display the boat and envelope configuration, respectively. The crystal structure contains weak C—H···N and C—H···S hydrogen bonding (Table 1).

Experimental

A mixture of 5-bromo2,4-dichloro-6-methylpyrimidine (2.5 mmol, 0.61 g), each alkyl-2-phenylhydrazinecarbodithioates (2.5 mmol) and triethylamine (1 ml) in acetonitril (10 ml) were boiled under inert atmosphere for 3 h. After the reaction was completed, the mixture was cooled to room temperature, and then evaporated under reduced pressure. The residue was washed with water and crystallized with ethanol and then washed with petroleum ether 40–60 to give pyrimido [4,5-e][1,3,4] thiadiazines. A mixture of previous obtained compound (5 mmol) in ethanol (20 ml) was heated under reflux with pyrrolidine (1.8 g) for 4 h. The solvent was removed and the residue was washed with water and then crystallized from ethanol to give the title crystals.

Refinement

Methyl H atoms were placed in calculated positions with C—H = 0.98 Å and torsion angles were refined to fif the electron density, Uiso(H) = 1.5Ueq(C). Other H atoms were placed in calculated positions with C—H = 0.95 (aromatic) and 0.99 Å (methylene), and refined in riding mode with Uiso(H) = 1.2Ueq(C).

Figures

Fig. 1.
The molecular structure of the title compound with 30% probability displacement (arbitrary spheres for H atoms).

Crystal data

C18H21N5S2Dx = 1.385 Mg m3
Mr = 371.52Melting point: 407 K
Orthorhombic, P212121Mo Kα radiation λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 9869 reflections
a = 8.3601 (2) Åθ = 2.2–30.5º
b = 10.3596 (3) ŵ = 0.31 mm1
c = 20.5754 (6) ÅT = 100 (2) K
V = 1781.98 (8) Å3Prism, colorless
Z = 40.43 × 0.34 × 0.25 mm
F000 = 784

Data collection

Bruker APEXII CCD area-detector diffractometer6479 independent reflections
Radiation source: fine-focus sealed tube5952 reflections with I > 2σ(I)
Monochromator: graphiteRint = 0.042
T = 100(2) Kθmax = 32.6º
[var phi] and ω scansθmin = 2.0º
Absorption correction: multi-scan(APEX2; Bruker, 2005)h = −12→12
Tmin = 0.878, Tmax = 0.927k = −15→15
36558 measured reflectionsl = −31→31

Refinement

Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.031  w = 1/[σ2(Fo2) + (0.04P)2 + 0.35P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.076(Δ/σ)max = 0.001
S = 1.01Δρmax = 0.39 e Å3
6479 reflectionsΔρmin = −0.24 e Å3
228 parametersExtinction correction: none
Primary atom site location: structure-invariant direct methodsAbsolute structure: Flack (1983), 2828 Friedel pairs
Secondary atom site location: difference Fourier mapFlack parameter: −0.01 (4)

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 (Å2)

xyzUiso*/Ueq
S10.22775 (4)0.63689 (3)0.139002 (14)0.01803 (7)
S20.13141 (4)0.84992 (3)0.054416 (14)0.01782 (7)
N10.19500 (13)0.60797 (10)0.01133 (5)0.01500 (19)
N20.15503 (13)0.65520 (9)−0.05106 (5)0.01352 (18)
N30.25257 (12)0.79575 (9)−0.13046 (5)0.01259 (18)
N40.32207 (12)1.01589 (9)−0.10384 (5)0.01291 (18)
N50.32568 (13)0.93935 (9)−0.20956 (5)0.01266 (18)
C10.18653 (15)0.68568 (11)0.05930 (6)0.0150 (2)
C20.20870 (15)0.77788 (11)−0.06931 (5)0.0123 (2)
C30.29962 (14)0.91713 (11)−0.14572 (5)0.01168 (19)
C40.28199 (15)0.99345 (11)−0.04183 (5)0.0132 (2)
C50.21638 (15)0.87583 (11)−0.02250 (5)0.0133 (2)
C60.24582 (16)0.46325 (12)0.13017 (6)0.0178 (2)
H6A0.23090.42250.17330.021*
H6B0.15920.43200.10140.021*
C70.40534 (17)0.42034 (15)0.10245 (7)0.0253 (3)
H7A0.40780.32590.09950.038*
H7B0.49190.44990.13090.038*
H7C0.41940.45740.05900.038*
C80.13997 (14)0.55459 (11)−0.09830 (5)0.0126 (2)
C90.04771 (15)0.57732 (12)−0.15373 (6)0.0151 (2)
H9A−0.00240.6587−0.15990.018*
C100.02966 (15)0.48028 (13)−0.19981 (6)0.0170 (2)
H10A−0.03080.4963−0.23810.020*
C110.09974 (15)0.35941 (13)−0.19027 (6)0.0178 (2)
H11A0.08660.2932−0.22170.021*
C120.18862 (15)0.33680 (11)−0.13451 (6)0.0167 (2)
H12A0.23510.2543−0.12760.020*
C130.21026 (15)0.43426 (11)−0.08857 (6)0.0151 (2)
H13A0.27270.4186−0.05080.018*
C140.39636 (15)1.05860 (11)−0.23480 (6)0.0137 (2)
H14A0.46451.1009−0.20170.016*
H14B0.31261.1199−0.24910.016*
C150.49585 (15)1.01128 (13)−0.29226 (6)0.0163 (2)
H15A0.60280.9815−0.27800.020*
H15B0.50871.0797−0.32540.020*
C160.39505 (16)0.89890 (12)−0.31828 (6)0.0163 (2)
H16A0.30430.9306−0.34470.020*
H16B0.46070.8394−0.34490.020*
C170.33637 (16)0.83293 (11)−0.25639 (6)0.0151 (2)
H17A0.23060.7921−0.26320.018*
H17B0.41320.7665−0.24160.018*
C180.30455 (17)1.10308 (12)0.00497 (6)0.0187 (2)
H18A0.38451.1632−0.01230.028*
H18B0.34121.06930.04690.028*
H18C0.20271.14840.01090.028*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
S10.02582 (15)0.01779 (13)0.01048 (11)−0.00161 (12)0.00034 (11)0.00230 (10)
S20.02715 (16)0.01428 (12)0.01203 (12)0.00202 (12)0.00653 (11)0.00012 (10)
N10.0204 (5)0.0137 (4)0.0109 (4)−0.0006 (4)0.0009 (4)0.0031 (3)
N20.0203 (5)0.0105 (4)0.0098 (4)−0.0011 (4)0.0010 (3)0.0008 (3)
N30.0161 (5)0.0108 (4)0.0109 (4)0.0005 (3)0.0010 (3)0.0011 (3)
N40.0158 (5)0.0110 (4)0.0119 (4)0.0002 (4)0.0005 (3)0.0002 (3)
N50.0181 (5)0.0095 (4)0.0104 (4)0.0000 (3)0.0019 (3)0.0002 (3)
C10.0188 (5)0.0144 (5)0.0117 (5)−0.0013 (4)0.0020 (4)0.0030 (4)
C20.0139 (5)0.0110 (4)0.0119 (5)0.0008 (4)0.0017 (4)0.0005 (4)
C30.0125 (5)0.0118 (4)0.0108 (4)0.0018 (4)0.0006 (4)0.0012 (4)
C40.0162 (5)0.0114 (4)0.0120 (4)0.0012 (4)−0.0002 (4)−0.0005 (4)
C50.0176 (5)0.0121 (5)0.0102 (4)0.0014 (4)0.0021 (4)0.0009 (4)
C60.0181 (6)0.0169 (5)0.0183 (5)−0.0004 (4)0.0000 (4)0.0056 (4)
C70.0201 (6)0.0296 (7)0.0261 (7)0.0060 (6)−0.0007 (5)0.0019 (5)
C80.0144 (5)0.0109 (4)0.0124 (4)−0.0020 (4)0.0023 (4)−0.0006 (4)
C90.0160 (5)0.0135 (5)0.0158 (5)−0.0003 (4)0.0001 (4)0.0014 (4)
C100.0160 (6)0.0189 (6)0.0162 (5)−0.0023 (4)−0.0012 (4)−0.0011 (4)
C110.0185 (6)0.0160 (5)0.0189 (5)−0.0034 (5)0.0021 (4)−0.0051 (4)
C120.0188 (5)0.0118 (5)0.0193 (5)−0.0008 (4)0.0035 (4)−0.0003 (4)
C130.0170 (6)0.0131 (5)0.0152 (5)0.0000 (4)0.0013 (4)0.0014 (4)
C140.0161 (5)0.0117 (5)0.0133 (5)−0.0009 (4)0.0013 (4)0.0024 (4)
C150.0165 (5)0.0202 (6)0.0122 (5)−0.0021 (4)0.0011 (4)0.0003 (4)
C160.0199 (6)0.0187 (5)0.0104 (5)−0.0015 (5)0.0010 (4)0.0006 (4)
C170.0216 (6)0.0115 (5)0.0123 (5)0.0006 (4)0.0019 (4)−0.0009 (4)
C180.0282 (7)0.0136 (5)0.0144 (5)−0.0019 (5)−0.0004 (5)−0.0031 (4)

Geometric parameters (Å, °)

S1—C11.7502 (12)C8—C91.3968 (16)
S1—C61.8144 (13)C9—C101.3901 (17)
S2—C51.7553 (11)C9—H9A0.9500
S2—C11.7657 (12)C10—C111.3963 (19)
N1—C11.2757 (15)C10—H10A0.9500
N1—N21.4137 (13)C11—C121.3868 (18)
N2—C21.3991 (14)C11—H11A0.9500
N2—C81.4307 (15)C12—C131.3948 (16)
N3—C21.3235 (14)C12—H12A0.9500
N3—C31.3545 (14)C13—H13A0.9500
N4—C41.3394 (14)C14—C151.5264 (17)
N4—C31.3508 (14)C14—H14A0.9900
N5—C31.3512 (14)C14—H14B0.9900
N5—C141.4646 (15)C15—C161.5337 (18)
N5—C171.4670 (15)C15—H15A0.9900
C2—C51.4005 (15)C15—H15B0.9900
C4—C51.3942 (15)C16—C171.5261 (16)
C4—C181.5008 (16)C16—H16A0.9900
C6—C71.5171 (19)C16—H16B0.9900
C6—H6A0.9900C17—H17A0.9900
C6—H6B0.9900C17—H17B0.9900
C7—H7A0.9800C18—H18A0.9800
C7—H7B0.9800C18—H18B0.9800
C7—H7C0.9800C18—H18C0.9800
C8—C131.3926 (16)
C1—S1—C6102.06 (6)C8—C9—H9A120.2
C5—S2—C195.34 (5)C9—C10—C11120.48 (12)
C1—N1—N2118.10 (10)C9—C10—H10A119.8
C2—N2—N1118.84 (9)C11—C10—H10A119.8
C2—N2—C8120.50 (9)C12—C11—C10119.50 (11)
N1—N2—C8112.67 (9)C12—C11—H11A120.2
C2—N3—C3115.51 (10)C10—C11—H11A120.2
C4—N4—C3116.20 (10)C11—C12—C13120.52 (11)
C3—N5—C14123.61 (10)C11—C12—H12A119.7
C3—N5—C17121.36 (9)C13—C12—H12A119.7
C14—N5—C17112.11 (9)C8—C13—C12119.73 (11)
N1—C1—S1122.13 (9)C8—C13—H13A120.1
N1—C1—S2125.35 (9)C12—C13—H13A120.1
S1—C1—S2112.52 (7)N5—C14—C15102.92 (9)
N3—C2—N2118.10 (10)N5—C14—H14A111.2
N3—C2—C5122.66 (10)C15—C14—H14A111.2
N2—C2—C5119.23 (10)N5—C14—H14B111.2
N4—C3—N5117.95 (10)C15—C14—H14B111.2
N4—C3—N3126.56 (10)H14A—C14—H14B109.1
N5—C3—N3115.49 (10)C14—C15—C16102.40 (10)
N4—C4—C5121.46 (10)C14—C15—H15A111.3
N4—C4—C18116.64 (10)C16—C15—H15A111.3
C5—C4—C18121.85 (10)C14—C15—H15B111.3
C4—C5—C2117.07 (10)C16—C15—H15B111.3
C4—C5—S2123.37 (8)H15A—C15—H15B109.2
C2—C5—S2119.38 (9)C17—C16—C15103.02 (9)
C7—C6—S1113.66 (10)C17—C16—H16A111.2
C7—C6—H6A108.8C15—C16—H16A111.2
S1—C6—H6A108.8C17—C16—H16B111.2
C7—C6—H6B108.8C15—C16—H16B111.2
S1—C6—H6B108.8H16A—C16—H16B109.1
H6A—C6—H6B107.7N5—C17—C16103.36 (9)
C6—C7—H7A109.5N5—C17—H17A111.1
C6—C7—H7B109.5C16—C17—H17A111.1
H7A—C7—H7B109.5N5—C17—H17B111.1
C6—C7—H7C109.5C16—C17—H17B111.1
H7A—C7—H7C109.5H17A—C17—H17B109.1
H7B—C7—H7C109.5C4—C18—H18A109.5
C13—C8—C9120.08 (11)C4—C18—H18B109.5
C13—C8—N2121.16 (10)H18A—C18—H18B109.5
C9—C8—N2118.72 (10)C4—C18—H18C109.5
C10—C9—C8119.66 (11)H18A—C18—H18C109.5
C10—C9—H9A120.2H18B—C18—H18C109.5
C1—N1—N2—C241.93 (16)C18—C4—C5—S28.17 (17)
C1—N1—N2—C8−168.98 (11)N3—C2—C5—C4−3.72 (18)
N2—N1—C1—S1178.19 (9)N2—C2—C5—C4175.25 (11)
N2—N1—C1—S2−1.02 (17)N3—C2—C5—S2171.64 (10)
C6—S1—C1—N1−8.61 (13)N2—C2—C5—S2−9.38 (16)
C6—S1—C1—S2170.70 (7)C1—S2—C5—C4−147.93 (11)
C5—S2—C1—N1−33.47 (13)C1—S2—C5—C237.01 (11)
C5—S2—C1—S1147.25 (7)C1—S1—C6—C778.51 (11)
C3—N3—C2—N2178.42 (10)C2—N2—C8—C13127.99 (12)
C3—N3—C2—C5−2.60 (18)N1—N2—C8—C13−20.53 (15)
N1—N2—C2—N3143.21 (11)C2—N2—C8—C9−54.47 (15)
C8—N2—C2—N3−3.42 (17)N1—N2—C8—C9157.01 (11)
N1—N2—C2—C5−35.81 (16)C13—C8—C9—C10−1.54 (18)
C8—N2—C2—C5177.56 (11)N2—C8—C9—C10−179.11 (11)
C4—N4—C3—N5174.47 (11)C8—C9—C10—C111.60 (19)
C4—N4—C3—N3−5.39 (18)C9—C10—C11—C12−0.37 (19)
C14—N5—C3—N48.23 (17)C10—C11—C12—C13−0.94 (18)
C17—N5—C3—N4167.32 (11)C9—C8—C13—C120.25 (18)
C14—N5—C3—N3−171.89 (10)N2—C8—C13—C12177.76 (11)
C17—N5—C3—N3−12.81 (16)C11—C12—C13—C81.00 (18)
C2—N3—C3—N47.60 (18)C3—N5—C14—C15144.67 (11)
C2—N3—C3—N5−172.26 (10)C17—N5—C14—C15−16.12 (13)
C3—N4—C4—C5−1.88 (17)N5—C14—C15—C1634.32 (12)
C3—N4—C4—C18−179.27 (11)C14—C15—C16—C17−40.28 (12)
N4—C4—C5—C26.08 (18)C3—N5—C17—C16−170.29 (11)
C18—C4—C5—C2−176.66 (12)C14—N5—C17—C16−9.01 (13)
N4—C4—C5—S2−169.08 (9)C15—C16—C17—N530.31 (13)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C12—H12A···N4i0.952.623.5630 (15)172
C15—H15B···S2ii0.992.833.6264 (13)138

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: XU2431).

References

  • Bakavoli, M., Nikpour, M. & Rahimizadeh, M. (2006). Phosphorus Sulfur Silicon Relat. Elem., 180, 2265–2268.
  • Bakavoli, M., Nikpour, M. & Rahimizadeh, M. (2007). J. Heterocycl. Chem.44, 463–465.
  • Bakavoli, M., Rahimizadeh, M., Shiri, A., Eshghi, H. & Nikpour, M. (2008). Heterocycles. In the press.
  • Bruker (2005). APEX2 Bruker AXS Inc., Madison, Wisconsin, USA.
  • Elliott, A. J. (1981). J. Heterocycl. Chem.18, 799–800.
  • Flack, H. D. (1983). Acta Cryst. A39, 876–881.
  • Rahimizadeh, M., Heravi, M. M. & Malekan, A. (1997). Indian J. Heterocycl. Chem.6, 223–224.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]

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