(1R,3S)-Camphoramic acid

The title chiral compound, 3-amino­carbonyl-1,2,2-tri­methyl­cyclo­pentane-1-carboxylic acid, C₁₀H₁₇NO₃, was prepared from (1R,3S)-camphoric acid. The five-membered ring adopts a conformation which is intermediate between a twist and an envelope. Elongations of the C-C bonds and contractions of the C-C-C bond angles are observed within the five-membered ring. A ¹H NMR spectrum was recorded to assist in distinguishing the amide group from the carboxyl group.

S1. Comment

The title compound, (I), was prepared from 1R,3S-camphoric acid and used as a chiral agent to separate racemic mandelic acid in our laboratory (Hu et al., 2001). In order to compare possible structural variations of (I) between its free and complex states, we have determined its structure and the results are presented here. \sch

The absolute configuration of (I) could not be determined reliably. Since the specific optical rotation [α]_D²⁰ value of 24.96° agrees with that reported previously for 1R,3S-camphoramic acid (Faigle & Karrer, 1962), the present refinements were performed with the 1R,3S-configuration, the same as the camphoric acid starting material.

A perspective molecular structure of (I) is presented in Fig. 1 and selected geometric parameters are listed in Table 1. A l l bond distances and angles agree well with those found in a molecular complex of camphoramic acid with mandelic acid (Hu et al., 2001). Thus, (I) shows little or no structural change upon forming complexes with other molecules.

Compound (I) can be viewed as a cyclopentane derivative with methyl and carboxyl groups on C1, two methyl groups on C2 and an amide group on C3. In order to establish the conformation of the five-membered ring, the ring-puckering coordinates and internal Cartesian coordinates (Cremer & Pople, 1975) were calculated. With atom C4 at the apex, the puckering coordinates q₂ and ϕ₂ are 0.434 (3) Å and -98.8 (4)°, respectively. This ϕ₂ value near to -90° suggests a twist conformation of the ring, with the twist axis through C4. The conformation of the five-membered ring is also near an envelope, with C1 at the flap position. Atom C1 lies 0.653 (3) Å from the best plane of the other four atoms, which exhibit a maximum deviation of -0.040 (3) Å (C4).

Two somewhat elongated C—C distances [C1—C2 1.568 (4) and C2—C3 1.574 (4) Å] and one contracted bond angle [C1—C2—C3 100.9 (2)°] are observed within the five-membered ring. They agree well with the corresponding values [1.561 (7) and 1.580 (7) Å, and 101.6 (4)°] found in a molecular complex of (I) with mandelic acid (Hu et al., 2001). As the structurally similar camphoric acid differs from (I) by having a carboxylic acid group on C3 instead of an aminocarbonyl group, camphoric acid structures can also be used for comparing the above-mentioned structural features. Similar elongation of C—C distances involving atoms C1, C2 and C3 was also found in several 1R,3S-camphoric acid structures (Santis et al., 1997; Goswami et al., 2000; Barnes et al., 1991; Calderon et al., 1994). These deformations may be explained by intramolecular repulsion between closely situated methyl and carboxyl groups.

The C10—N1 distance of 1.326 (4) Å shows the existence of electron delocalization within the amide moiety.

Hydrogen-bond parameters for (I) are listed in Table 2. Adjacent molecules are linked by hydrogen bonds between amide and carboxyl groups to form a supramolecular structure. Weak intramolecular C—H···O bonding interactions involving carbonyl O atoms are observed, which seem to affect the conformation of the carboxyl and amide groups.

Although elemental analysis of C, H and N is consistent with the fact that only one carboxyl group of camphoric acid has been transformed into an amide group in the present synthesis, it is still necessary to distinguish the amide group from the carboxyl group. The reasonable isotropic displacement parameters on the N and O atoms confirmed the present structure of 1R,3S for (I). Inverting the N,O assignment gave unusually large and small displacement parameters, and a higher R factor of 0.054 resulted.

S2. Experimental

A mixture of 1R,3S-camphoric acid (20 g) and thionyl chloride (25 ml) was heated at 348 K with stirring for 4 h. Once the camphoric acid had completely dissolved, the excess thionyl chloride was removed under reduced pressure in a rotary evaporator to give a white intermediate, camphoryl chloride. The camphoryl chloride was treated with saturated aqueous ammonia (50 ml) for 1.5 h at room temperature. The reaction mixture was adjusted with aqueous HCl to pH6 and stirred for 1 h at 318 K, giving a white precipitate. The precipitate was separated by filtration, washed twice with water and dried under reduced pressure to obtain the title compound, (I). Re-crystallization of (I) from an aqueous solution gave well shaped single crystals. C, H and N were analysed using a Carlo-Erba 1160 instrument. Analysis calculated for C₁₀H₁₇NO₃: C 60.30, H 8.54, N 7.04%; found: C 59.78, H 8.64, N 7.10%. The ¹H NMR spectrum of (I) was recorded on an Avance DMX500 spectrometer in CDCl₃; δ, p.p.m.: 0.95 (3H), 1.24–1.34 (6H), 1.57–2.39 (4H), 2.86 (1H), 5.62–5.93 (2H). The specific optical rotation of the sample was determined using a WZZ-1S instrument at 293 K.

S3. Refinement

H atoms were located from a difference Fourier map. Methyl H atoms were placed in calculated positions with C—H = 0.96 Å. All H atoms were included in the final cycles of least-squares refinement with fixed coordinates and with U_iso = 0.08 Ų.

Computing details

Data collection: MSC/AFC Diffractometer Control Software (Molecular Structure Corporation, 1992); cell refinement: MSC/AFC Diffractometer Control Software; data reduction: TEXSAN (Molecular Structure Corporation, 1985); program(s) used to solve structure: SHELXS93 (Sheldrick, 1993); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP (Siemens, 1994).

Figures

Fig. 1. A view of the molecular structure of (I) showing 30% probability displacement ellipsoids. H atoms are shown as small spheres of arbitrary radii.

3-aminocarbonyl-1,2,2-trimethylcyclopentane-1-carboxylic acid

Crystal data

C10H17NO3	Dx = 1.280 Mg m^−3
Mr = 199.25	Mo Kα radiation, λ = 0.71069 Å
Orthorhombic, P212121	Cell parameters from 22 reflections
a = 7.2389 (14) Å	θ = 8.6–12.5°
b = 11.2125 (14) Å	µ = 0.09 mm^−1
c = 12.7427 (15) Å	T = 298 K
V = 1034.3 (2) Å^3	Prism, colourless
Z = 4	0.54 × 0.48 × 0.36 mm
F(000) = 432

Data collection

Rigaku AFC-7S diffractometer	Rint = 0.000
Radiation source: fine-focus sealed tube	θmax = 25.0°, θmin = 2.4°
Graphite monochromator	h = 0→8
ω/2θ scans	k = 0→13
1073 measured reflections	l = 0→15
1073 independent reflections	3 standard reflections every 100 reflections
941 reflections with I > 2σ(I)	intensity decay: 0.3%

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)] = 0.040	Hydrogen site location: difference Fourier map
wR(F^2) = 0.111	H-atom parameters not refined
S = 1.04	w = 1/[σ^2(Fo^2) + (0.0701P)^2 + 0.2891P] where P = (Fo^2 + 2Fc^2)/3
1073 reflections	(Δ/σ)max < 0.001
127 parameters	Δρmax = 0.19 e Å^−3
0 restraints	Δρmin = −0.16 e Å^−3

Special details

Experimental. Data collection were performed with a scan width of Δω = (1.0 + 0.30 tan θ)° and a scan rate of less than 16°min^-1 in ω.

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
O1	0.7153 (3)	0.3735 (2)	0.3314 (2)	0.0629 (7)
O2	0.5549 (3)	0.5188 (2)	0.4053 (2)	0.0669 (7)
O3	0.1559 (3)	0.17002 (19)	0.08352 (15)	0.0485 (6)
N1	−0.0873 (3)	0.2863 (2)	0.12091 (19)	0.0511 (7)
C1	0.3878 (4)	0.3439 (3)	0.3613 (2)	0.0401 (7)
C2	0.2788 (4)	0.3705 (2)	0.2576 (2)	0.0351 (6)
C3	0.1408 (4)	0.2621 (2)	0.2552 (2)	0.0351 (6)
C4	0.2409 (4)	0.1582 (3)	0.3096 (2)	0.0454 (7)
C5	0.4188 (5)	0.2083 (3)	0.3537 (3)	0.0525 (8)
C6	0.2757 (5)	0.3726 (4)	0.4585 (3)	0.0756 (13)
C7	0.5706 (4)	0.4107 (3)	0.3646 (2)	0.0443 (7)
C8	0.1753 (5)	0.4893 (3)	0.2575 (3)	0.0649 (10)
C9	0.4081 (5)	0.3698 (3)	0.1618 (2)	0.0493 (7)
C10	0.0711 (4)	0.2342 (2)	0.1460 (2)	0.0375 (6)
H1A	−0.1438	0.2770	0.0589	0.080*
H1B	−0.1646	0.3223	0.1791	0.080*
H2	0.6583	0.5584	0.3987	0.080*
H3	0.0378	0.2818	0.3000	0.080*
H4A	0.2504	0.0915	0.2615	0.080*
H4B	0.1574	0.1230	0.3609	0.080*
H5A	0.4207	0.1750	0.4206	0.080*
H5B	0.5263	0.1866	0.3134	0.080*
H6A	0.1596	0.3306	0.4561	0.080*
H6B	0.2512	0.4572	0.4610	0.080*
H6C	0.3423	0.3495	0.5201	0.080*
H8A	0.0934	0.4921	0.3165	0.080*
H8B	0.1054	0.4963	0.1937	0.080*
H8C	0.2626	0.5535	0.2619	0.080*
H9A	0.4749	0.2959	0.1598	0.080*
H9B	0.4933	0.4350	0.1669	0.080*
H9C	0.3361	0.3779	0.0988	0.080*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0323 (10)	0.0637 (14)	0.0929 (17)	−0.0013 (11)	0.0059 (12)	−0.0131 (14)
O2	0.0510 (13)	0.0675 (15)	0.0820 (16)	−0.0230 (12)	0.0156 (13)	−0.0343 (13)
O3	0.0484 (11)	0.0553 (12)	0.0417 (10)	0.0141 (11)	−0.0063 (10)	−0.0066 (10)
N1	0.0397 (13)	0.0625 (16)	0.0510 (13)	0.0125 (13)	−0.0121 (12)	−0.0035 (13)
C1	0.0342 (13)	0.0493 (15)	0.0367 (13)	−0.0075 (12)	0.0035 (12)	−0.0034 (12)
C2	0.0301 (13)	0.0330 (13)	0.0422 (14)	0.0016 (12)	0.0021 (12)	0.0010 (12)
C3	0.0303 (12)	0.0384 (14)	0.0365 (14)	−0.0016 (12)	0.0002 (11)	0.0002 (11)
C4	0.0513 (17)	0.0405 (15)	0.0444 (15)	−0.0063 (14)	−0.0131 (14)	0.0070 (13)
C5	0.0489 (17)	0.0474 (16)	0.0612 (18)	−0.0065 (15)	−0.0175 (16)	0.0145 (15)
C6	0.070 (2)	0.112 (3)	0.0449 (16)	−0.040 (3)	0.0247 (18)	−0.024 (2)
C7	0.0396 (15)	0.0540 (17)	0.0392 (14)	−0.0097 (15)	−0.0002 (13)	−0.0052 (14)
C8	0.0486 (17)	0.0371 (16)	0.109 (3)	0.0076 (15)	0.002 (2)	−0.0007 (18)
C9	0.0506 (17)	0.0584 (18)	0.0390 (13)	−0.0108 (16)	0.0038 (14)	0.0042 (14)
C10	0.0322 (12)	0.0389 (13)	0.0412 (13)	0.0013 (12)	−0.0027 (12)	0.0033 (12)

Geometric parameters (Å, º)

O1—C7	1.204 (4)	C3—H3	0.965
O2—C7	1.324 (4)	C4—C5	1.513 (4)
O2—H2	0.874	C4—H4A	0.969
O3—C10	1.236 (3)	C4—H4B	0.974
N1—C10	1.326 (4)	C5—H5A	0.931
N1—H1A	0.896	C5—H5B	0.963
N1—H1B	1.013	C6—H6A	0.96
C1—C6	1.515 (4)	C6—H6B	0.96
C1—C7	1.521 (4)	C6—H6C	0.96
C1—C5	1.541 (4)	C8—H8A	0.96
C1—C2	1.568 (4)	C8—H8B	0.96
C2—C8	1.529 (4)	C8—H8C	0.96
C2—C9	1.539 (4)	C9—H9A	0.96
C2—C3	1.574 (4)	C9—H9B	0.96
C3—C10	1.513 (4)	C9—H9C	0.96
C3—C4	1.538 (4)
C7—O2—H2	110.7	C4—C5—H5A	101.8
C10—N1—H1A	123.8	C1—C5—H5A	109.8
C10—N1—H1B	118.5	C4—C5—H5B	113.4
H1A—N1—H1B	116.1	C1—C5—H5B	113.6
C6—C1—C7	109.9 (2)	H5A—C5—H5B	112.0
C6—C1—C5	109.8 (3)	C1—C6—H6A	109.5
C7—C1—C5	111.2 (3)	C1—C6—H6B	109.5
C6—C1—C2	112.3 (3)	H6A—C6—H6B	109.5
C7—C1—C2	111.5 (2)	C1—C6—H6C	109.4
C5—C1—C2	102.0 (2)	H6A—C6—H6C	109.5
C8—C2—C9	107.6 (3)	H6B—C6—H6C	109.5
C8—C2—C1	114.4 (3)	O1—C7—O2	122.0 (3)
C9—C2—C1	111.2 (2)	O1—C7—C1	125.2 (3)
C8—C2—C3	111.2 (2)	O2—C7—C1	112.7 (3)
C9—C2—C3	111.5 (2)	C2—C8—H8A	109.4
C1—C2—C3	100.9 (2)	C2—C8—H8B	109.5
C10—C3—C4	114.6 (2)	H8A—C8—H8B	109.5
C10—C3—C2	112.9 (2)	C2—C8—H8C	109.5
C4—C3—C2	106.1 (2)	H8A—C8—H8C	109.5
C10—C3—H3	109.5	H8B—C8—H8C	109.5
C4—C3—H3	105.7	C2—C9—H9A	109.5
C2—C3—H3	107.6	C2—C9—H9B	109.4
C5—C4—C3	106.7 (2)	H9A—C9—H9B	109.5
C5—C4—H4A	117.4	C2—C9—H9C	109.5
C3—C4—H4A	109.4	H9A—C9—H9C	109.5
C5—C4—H4B	115.5	H9B—C9—H9C	109.5
C3—C4—H4B	108.5	O3—C10—N1	122.1 (3)
H4A—C4—H4B	99.0	O3—C10—C3	123.2 (2)
C4—C5—C1	105.4 (2)	N1—C10—C3	114.8 (2)
C6—C1—C2—C8	44.3 (3)	C2—C3—C4—C5	6.7 (3)
C7—C1—C2—C8	−79.5 (3)	C3—C4—C5—C1	20.5 (3)
C5—C1—C2—C8	161.8 (3)	C6—C1—C5—C4	79.6 (3)
C6—C1—C2—C9	166.4 (3)	C7—C1—C5—C4	−158.6 (2)
C7—C1—C2—C9	42.6 (3)	C2—C1—C5—C4	−39.7 (3)
C5—C1—C2—C9	−76.1 (3)	C6—C1—C7—O1	145.1 (4)
C6—C1—C2—C3	−75.2 (3)	C5—C1—C7—O1	23.4 (4)
C7—C1—C2—C3	161.0 (2)	C2—C1—C7—O1	−89.7 (4)
C5—C1—C2—C3	42.3 (3)	C6—C1—C7—O2	−37.1 (4)
C8—C2—C3—C10	81.6 (3)	C5—C1—C7—O2	−158.8 (3)
C9—C2—C3—C10	−38.5 (3)	C2—C1—C7—O2	88.1 (3)
C1—C2—C3—C10	−156.6 (2)	C4—C3—C10—O3	−36.5 (4)
C8—C2—C3—C4	−152.1 (3)	C2—C3—C10—O3	85.1 (3)
C9—C2—C3—C4	87.8 (3)	C4—C3—C10—N1	145.0 (3)
C1—C2—C3—C4	−30.4 (2)	C2—C3—C10—N1	−93.5 (3)
C10—C3—C4—C5	131.9 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O3^i	0.896	2.398	3.238 (4)	156
N1—H1B···O1^ii	1.013	2.203	3.193 (4)	165
O2—H2···O3^iii	0.874	1.851	2.698 (4)	163

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