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The title compound, C12H19N3O2, is an unusual product of silica-catalyzed intermolecular condensation of α-amino­isobutyric acid. The mol­ecule has three types of C—N bonds: a double bond, a cis-amide bond and single bonds, two of which are typical and two having intermediate lengths due to π-electron delocalization between C=N and C=O groups. The cis-amide moieties interact to form dimers via hydrogen bonds which stack in parallel layers.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270100002766/da1114sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270100002766/da1114Isup2.hkl
Contains datablock I

CCDC reference: 145550

Comment top

The large family of imidazo[1,2-a]pyrazines (Basiuk, 1997) includes a few examples of rather exotic bicyclic amidine-type compounds composed of three α-amino acid residues. \sch

The formation of this bicyclic amidine system was first reported more than three decades ago (Jones et al., 1963, 1965). During subsequent years, several groups worked on different aspects of the bicyclic amidine chemistry (Titlestad, 1972; Ali et al., 1973; Rothe et al., 1979; Ali & Khatun, 1985; Ali, 1990; Yamada et al., 1993; Saviano et al., 1996). As a result, approximately ten compounds of this class have been reported. The prerequisites of their synthesis have been (1) the use of tri- to pentapeptide precursors, in some cases along with rather drastic activating reagents such as phosphorus pentachloride or thionyl chloride (Titlestad, 1972; Ali et al., 1973; Ali & Khatun, 1985; Ali, 1990); and (2) the inclusion of sterically hindered α-amino acids into molecules of the peptide starting material; such acids include α-aminoisobutyric acid (Titlestad, 1972; Ali et al., 1973; Ali & Khatun, 1985; Ali, 1990) and α,α-diisopropylglycine (Yamada et al., 1993; Saviano et al., 1996). X-ray structures of these compounds are apparently only known for the bicyclic amidine with R1 = R2 = R5 = iPr and R3 = R4 = R6 = H (Saviano et al., 1996).

Our recent studies of amino acid pyrolysis products by gas chromatography-Fourier transform infrared spectroscopy-mass spectrometry revealed that a direct formation of the bicyclic amidines is possible when simple amino acids (e.g., α-aminoisobutyric acid, alanine, valine, norvaline and leucine) are pyrolyzed at about 773 K (Basiuk, 1998; Basiuk & Navarro-González, 1998; Basiuk et al., 1998a), or even at 473–573 K but in the presence of silica gel as a dehydration catalyst (Basiuk & Navarro-González, 1997; Basiuk et al., 1998b). In the latter case, bicyclic amidine yields can reach the 1–10% level. Although the amidines form along with many other pyrolysis products, it was possible to separate the α-aminoisobutyric acid derivative (R1 = R2 = R3 = R4 = R5 = R6 = Me), (I), by means of recrystallization. In this paper we report the results of its X-ray diffraction analysis.

A view of the bicyclic amidine is shown in Fig. 1. In many regards, this compound is similar to the triisopropyl analog reported by Saviano et al. (1996). In particular, the double bond lengths are: 1.235 (2) for C2–O7, 1.215 (2) for C14–O17, and 1.271 (2) Å for C5–N12 [versus 1.233 (2), 1.215 (2) and 1.276 (2) Å for the triisopropyl analog]. Of the other C–N bonds existing in the molecule, N1–C2 is typical for cis-amides [1.331 (2) Å]; N1–C6, N4–C3 and N12–C13 are common single C–N bonds [1.461 (2), 1.480 (2) and 1.477 (2) Å, respectively]. The remaining two, N4–C5 and N4–C14, exhibit intermediate values [1.397 (2) and 1.390 (2) Å, respectively], thus pointing to an evident π-electron delocalization between the C5–N12 and C14–O17 double bonds.

The five-membered ring is planar within 0.009 (2) Å (atom C5), the six-membered ring deviates up to 0.097 (2) Å (atom C6) and has a slight boat conformation [puckering parameters: Q = 0.143 (2) Å, θ = 112.6 (8)°, ϕ = 125.5 (8)° (Cremer & Pople, 1975)].

Unlike the triisopropyl analog, crystals of the present bicyclic amidine do not display any crystallographic disorder. This is likely due to conformational rigidity of the α,α-dimethyl fragments in the α-aminoisobutyric residues, as compared to their isopropyl counterparts.

As might be expected, the present crystal structure includes a pattern of hydrogen bonding (Fig. 2) similar to that described by Saviano et al. (1996). Interaction between cis-amide moieties gives rise to the formation of hydrogen-bonded dimers: N1···O7 2.929 (2) Å, N1–H1···O7 161.5 (11)°. The dimers form parallel layers. There is also possible intramolecular bonding between O17 and methyl groups C9 and C8 due to weak C–H···O interactions. The corresponding length and angles are: C8···O17 3.191 (3) Å and C8–H8C···O17 119.1 (8)°; C9···O17 3.116 (3) Å and C9–H9A···O17 121.2 (7)°.

Experimental top

α-Aminoisobutyric acid from Sigma, and silica gel and solvents from Aldrich were used without further purification. Crystalline α-aminoisobutyric acid (4 g) was heated in the presence of silica gel (10 g) as dehydration catalyst in a continuously evacuated round-bottom flask at about 10 -1 Torr under 503–513 K. During the heating, the amino acid sublimed, reacted with the silica gel, and the resulting products along with unreacted amino acid condensed in the unheated flask neck. To increase conversion of the starting reagent into condensation products, the flask was opened and the sublimate was returned to the bottom of the flask to again make contact with the silica gel, and the procedure was repeated 2 more times. This triple sublimation took, in total, about 8 h. Crude sublimate was removed from the flask neck and washed with chloroform (3 × 20 ml). The resulting solution was evaporated to produce 0.27 g of an amorphous, rusty brown substance. Four-fold recrystallization from methanol gave the bicyclic condensation product as colorless needles. (yield 23 mg, 0.75%). Calculated for C12H19N3O2 (%): C 60.74, H 8.07, N 17.71. Found (%): C 60.79, H 8.13, N 17.68. IR (KBr): ν = 1736 (C=O stretch, imidazole ring), 1670 (C=O stretch, pyrazine ring), 1646 cm-1 (C=N stretch). 1H NMR (200 MHz, CDCl3): δ = 1.32 [s, 6H, CH3 (2-Me)], 1.65 [s, 6H, CH3 (5-Me)], 1.75 [s, 6H, CH3 (8-Me)].

Refinement top

Atom H1, on N1, was constrained to lie on the external bisector of the C2–N1–C6 angle, with the N–H distance free to refine and Uiso(H1) = 1.2 times Ueq(N1). The CH3 groups were allowed to rotate but not tip, and the C–H distances were allowed to refine (the same shifts were applied along all 3 C–H bonds in each group). Uiso(methyl H) was set to 1.5 times Ueq(methyl C).

Computing details top

Data collection: XSCANS (Siemens, 1994); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SHELXTL (Sheldrick, 1997); program(s) used to refine structure: SHELXTL; molecular graphics: PLATON99 (Spek, 1999); software used to prepare material for publication: PLATON99.

Figures top
[Figure 1] Fig. 1. Molecular structure drawn with 50% probability displacement elipsoids.
[Figure 2] Fig. 2. Packing diagram.
2,2,5,5,8,8-hexamethyl-4,5,7,8-tetrahydroimidazo[1,2-a]pyrazine- -3,6-dione top
Crystal data top
C12H19N3O2Z = 2
Mr = 237.30F(000) = 256
Triclinic, P1Dx = 1.233 Mg m3
a = 5.902 (1) ÅMo Kα radiation, λ = 0.71073 Å
b = 8.628 (2) ÅCell parameters from 20 reflections
c = 12.949 (2) Åθ = 20.0–21.4°
α = 95.02 (1)°µ = 0.09 mm1
β = 93.34 (1)°T = 289 K
γ = 102.45 (1)°Needle, colorless
V = 639.4 (2) Å30.40 × 0.30 × 0.20 mm
Data collection top
Siemens P4
diffractometer
Rint = 0.028
Radiation source: fine-focus sealed tubeθmax = 25.0°, θmin = 1.6°
Graphite monochromatorh = 71
ω scansk = 1010
2941 measured reflectionsl = 1515
2234 independent reflections3 standard reflections every 97 reflections
1621 reflections with I > 2σ(I) intensity decay: 0.019%
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.042Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.116H atoms treated by a mixture of independent and constrained refinement
S = 1.01 w = 1/[σ2(Fo2) + (0.0495P)2 + 0.1584P]
where P = (Fo2 + 2Fc2)/3
2234 reflections(Δ/σ)max < 0.001
167 parametersΔρmax = 0.17 e Å3
0 restraintsΔρmin = 0.22 e Å3
Crystal data top
C12H19N3O2γ = 102.45 (1)°
Mr = 237.30V = 639.4 (2) Å3
Triclinic, P1Z = 2
a = 5.902 (1) ÅMo Kα radiation
b = 8.628 (2) ŵ = 0.09 mm1
c = 12.949 (2) ÅT = 289 K
α = 95.02 (1)°0.40 × 0.30 × 0.20 mm
β = 93.34 (1)°
Data collection top
Siemens P4
diffractometer
Rint = 0.028
2941 measured reflections3 standard reflections every 97 reflections
2234 independent reflections intensity decay: 0.019%
1621 reflections with I > 2σ(I)
Refinement top
R[F2 > 2σ(F2)] = 0.0420 restraints
wR(F2) = 0.116H atoms treated by a mixture of independent and constrained refinement
S = 1.01Δρmax = 0.17 e Å3
2234 reflectionsΔρmin = 0.22 e Å3
167 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
xyzUiso*/Ueq
N10.3780 (3)0.03424 (19)0.12592 (13)0.0502 (5)
H10.4396 (18)0.0326 (19)0.0888 (11)0.060*
C20.4238 (4)0.1828 (2)0.09934 (14)0.0406 (5)
C30.3580 (3)0.3171 (2)0.16797 (13)0.0337 (4)
N40.2551 (3)0.25582 (16)0.26197 (11)0.0340 (4)
C50.2061 (3)0.0976 (2)0.28546 (13)0.0324 (4)
C60.2402 (3)0.0339 (2)0.20779 (14)0.0380 (5)
O70.5232 (3)0.21692 (16)0.02039 (11)0.0590 (5)
C80.1808 (4)0.3850 (3)0.10606 (15)0.0500 (6)
H8A0.038 (2)0.3018 (12)0.0880 (10)0.075*
H8B0.2463 (13)0.4217 (17)0.0420 (10)0.075*
H8C0.144 (2)0.4754 (16)0.1483 (7)0.075*
C90.5799 (4)0.4454 (2)0.20031 (16)0.0468 (5)
H9A0.5407 (7)0.5357 (14)0.2471 (10)0.070*
H9B0.6493 (16)0.4892 (13)0.1357 (8)0.070*
H9C0.6975 (17)0.3967 (7)0.2396 (10)0.070*
C100.3710 (5)0.1434 (3)0.26047 (18)0.0652 (8)
H10A0.400 (3)0.2246 (18)0.2085 (8)0.098*
H10B0.2774 (19)0.1953 (18)0.3129 (12)0.098*
H10C0.519 (3)0.0807 (10)0.2939 (13)0.098*
C110.0044 (5)0.1261 (3)0.1603 (2)0.0797 (9)
H11A0.0763 (19)0.0533 (13)0.1243 (14)0.120*
H11B0.091 (2)0.172 (2)0.2161 (9)0.120*
H11C0.0248 (6)0.214 (2)0.1091 (14)0.120*
N120.1222 (3)0.07327 (17)0.37233 (12)0.0403 (4)
C130.0975 (3)0.2296 (2)0.42087 (13)0.0346 (4)
C140.1876 (3)0.3467 (2)0.34367 (14)0.0358 (4)
C150.1580 (4)0.2249 (3)0.43498 (17)0.0488 (5)
H15A0.2490 (13)0.1998 (17)0.3657 (9)0.073*
H15B0.1744 (5)0.3310 (14)0.4674 (11)0.073*
H15C0.2185 (11)0.1407 (15)0.4811 (11)0.073*
C160.2412 (4)0.2735 (3)0.52520 (15)0.0511 (6)
H16A0.1831 (18)0.1941 (14)0.5734 (7)0.077*
H16B0.227 (2)0.3803 (16)0.5548 (7)0.077*
H16C0.406 (2)0.2748 (17)0.5150 (3)0.077*
O170.1979 (3)0.48949 (15)0.34949 (11)0.0527 (4)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0784 (14)0.0347 (9)0.0454 (10)0.0227 (9)0.0340 (9)0.0034 (7)
C20.0517 (13)0.0387 (11)0.0340 (10)0.0119 (9)0.0166 (9)0.0038 (8)
C30.0447 (11)0.0309 (9)0.0276 (9)0.0101 (8)0.0124 (8)0.0051 (7)
N40.0483 (10)0.0266 (8)0.0284 (8)0.0090 (7)0.0141 (7)0.0013 (6)
C50.0385 (10)0.0288 (9)0.0315 (9)0.0091 (8)0.0091 (8)0.0041 (7)
C60.0511 (12)0.0300 (9)0.0335 (10)0.0084 (8)0.0165 (9)0.0006 (7)
O70.0912 (12)0.0460 (9)0.0458 (8)0.0180 (8)0.0414 (9)0.0073 (7)
C80.0631 (14)0.0555 (13)0.0377 (11)0.0244 (11)0.0082 (10)0.0080 (9)
C90.0513 (13)0.0414 (11)0.0464 (12)0.0040 (9)0.0149 (10)0.0051 (9)
C100.109 (2)0.0441 (13)0.0581 (14)0.0423 (13)0.0303 (14)0.0105 (11)
C110.0658 (18)0.0862 (19)0.0690 (17)0.0074 (14)0.0143 (14)0.0370 (14)
N120.0579 (11)0.0321 (8)0.0349 (8)0.0142 (7)0.0188 (8)0.0050 (6)
C130.0476 (12)0.0297 (9)0.0290 (9)0.0130 (8)0.0133 (8)0.0000 (7)
C140.0469 (12)0.0294 (10)0.0321 (9)0.0104 (8)0.0102 (8)0.0010 (7)
C150.0518 (14)0.0485 (12)0.0486 (12)0.0135 (10)0.0158 (10)0.0042 (9)
C160.0591 (14)0.0583 (13)0.0359 (11)0.0129 (11)0.0065 (10)0.0026 (9)
O170.0838 (12)0.0297 (8)0.0481 (8)0.0158 (7)0.0254 (8)0.0021 (6)
Geometric parameters (Å, º) top
N1—C21.331 (2)C9—H9C1.0195
N1—C61.461 (2)C10—H10A0.9782
N1—H10.8705C10—H10B0.9782
C2—O71.235 (2)C10—H10C0.9782
C2—C31.529 (2)C11—H11A0.9965
C3—N41.480 (2)C11—H11B0.9965
C3—C81.526 (3)C11—H11C0.9965
C3—C91.531 (3)N12—C131.477 (2)
N4—C141.390 (2)C13—C141.520 (2)
N4—C51.397 (2)C13—C151.522 (3)
C5—N121.271 (2)C13—C161.525 (3)
C5—C61.504 (2)C14—O171.215 (2)
C6—C111.512 (3)C15—H15A0.9998
C6—C101.524 (3)C15—H15B0.9998
C8—H8A0.9834C15—H15C0.9998
C8—H8B0.9834C16—H16A0.9877
C8—H8C0.9834C16—H16B0.9877
C9—H9A1.0195C16—H16C0.9877
C9—H9B1.0195
C2—N1—C6129.94 (16)H9B—C9—H9C109.5
C2—N1—H1115.0C6—C10—H10A109.5
C6—N1—H1115.0C6—C10—H10B109.5
O7—C2—N1121.56 (17)H10A—C10—H10B109.5
O7—C2—C3118.11 (16)C6—C10—H10C109.5
N1—C2—C3120.32 (16)H10A—C10—H10C109.5
N4—C3—C8109.29 (15)H10B—C10—H10C109.5
N4—C3—C2110.39 (14)C6—C11—H11A109.5
C8—C3—C2108.88 (15)C6—C11—H11B109.5
N4—C3—C9109.43 (14)H11A—C11—H11B109.5
C8—C3—C9110.81 (16)C6—C11—H11C109.5
C2—C3—C9108.04 (15)H11A—C11—H11C109.5
C14—N4—C5107.13 (14)H11B—C11—H11C109.5
C14—N4—C3125.79 (14)C5—N12—C13106.70 (14)
C5—N4—C3127.08 (14)N12—C13—C14104.69 (13)
N12—C5—N4116.08 (15)N12—C13—C15109.61 (16)
N12—C5—C6123.44 (16)C14—C13—C15110.36 (16)
N4—C5—C6120.38 (15)N12—C13—C16110.88 (16)
N1—C6—C5109.77 (15)C14—C13—C16110.81 (16)
N1—C6—C11109.31 (18)C15—C13—C16110.37 (16)
C5—C6—C11108.76 (17)O17—C14—N4126.13 (17)
N1—C6—C10108.07 (17)O17—C14—C13128.50 (16)
C5—C6—C10110.26 (16)N4—C14—C13105.37 (14)
C11—C6—C10110.7 (2)C13—C15—H15A109.5
C3—C8—H8A109.5C13—C15—H15B109.5
C3—C8—H8B109.5H15A—C15—H15B109.5
H8A—C8—H8B109.5C13—C15—H15C109.5
C3—C8—H8C109.5H15A—C15—H15C109.5
H8A—C8—H8C109.5H15B—C15—H15C109.5
H8B—C8—H8C109.5C13—C16—H16A109.5
C3—C9—H9A109.5C13—C16—H16B109.5
C3—C9—H9B109.5H16A—C16—H16B109.5
H9A—C9—H9B109.5C13—C16—H16C109.5
C3—C9—H9C109.5H16A—C16—H16C109.5
H9A—C9—H9C109.5H16B—C16—H16C109.5
C6—N1—C2—O7172.0 (2)N12—C5—C6—N1169.57 (19)
C6—N1—C2—C39.3 (3)N4—C5—C6—N114.1 (2)
O7—C2—C3—N4176.31 (18)N12—C5—C6—C1170.9 (3)
N1—C2—C3—N42.5 (3)N4—C5—C6—C11105.5 (2)
O7—C2—C3—C863.7 (2)N12—C5—C6—C1050.6 (3)
N1—C2—C3—C8117.5 (2)N4—C5—C6—C10133.01 (19)
O7—C2—C3—C956.7 (2)N4—C5—N12—C131.5 (2)
N1—C2—C3—C9122.1 (2)C6—C5—N12—C13174.97 (17)
C8—C3—N4—C1464.0 (2)C5—N12—C13—C140.6 (2)
C2—C3—N4—C14176.27 (17)C5—N12—C13—C15117.76 (18)
C9—C3—N4—C1457.5 (2)C5—N12—C13—C16120.15 (18)
C8—C3—N4—C5115.6 (2)C5—N4—C14—O17178.0 (2)
C2—C3—N4—C54.1 (3)C3—N4—C14—O171.7 (3)
C9—C3—N4—C5122.87 (19)C5—N4—C14—C131.3 (2)
C14—N4—C5—N121.9 (2)C3—N4—C14—C13179.03 (17)
C3—N4—C5—N12178.43 (18)N12—C13—C14—O17178.8 (2)
C14—N4—C5—C6174.74 (17)C15—C13—C14—O1760.9 (3)
C3—N4—C5—C64.9 (3)C16—C13—C14—O1761.7 (3)
C2—N1—C6—C517.3 (3)N12—C13—C14—N40.5 (2)
C2—N1—C6—C11101.9 (3)C15—C13—C14—N4118.32 (17)
C2—N1—C6—C10137.6 (2)C16—C13—C14—N4119.13 (17)

Experimental details

Crystal data
Chemical formulaC12H19N3O2
Mr237.30
Crystal system, space groupTriclinic, P1
Temperature (K)289
a, b, c (Å)5.902 (1), 8.628 (2), 12.949 (2)
α, β, γ (°)95.02 (1), 93.34 (1), 102.45 (1)
V3)639.4 (2)
Z2
Radiation typeMo Kα
µ (mm1)0.09
Crystal size (mm)0.40 × 0.30 × 0.20
Data collection
DiffractometerSiemens P4
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
2941, 2234, 1621
Rint0.028
(sin θ/λ)max1)0.595
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.042, 0.116, 1.01
No. of reflections2234
No. of parameters167
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.17, 0.22

Computer programs: XSCANS (Siemens, 1994), XSCANS, SHELXTL (Sheldrick, 1997), SHELXTL, PLATON99 (Spek, 1999), PLATON99.

 

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