Methyl 3-[(tert-but­oxy­carbon­yl)amino]­benzoate

In the extended structure of the title compound, mol­ecular pairs are connected via N—H⋯O and C—H⋯O hydrogen bonds, generating inversion dimers characterized by R²₂(10) graph-set motifs. These dimers further associate through N—H⋯O and C—H⋯O inter­actions, forming supra­molecular layers lying parallel to the (104) crystallographic plane. Aromatic π–π stacking inter­actions and C—H⋯π contacts contribute to the tri-periodic supra­molecular architecture.

Abstract

In the extended structure of the title compound, C₁₃H₁₇NO₄, mol­ecular pairs are connected via N—H⋯O and C—H⋯O hydrogen bonds, generating inversion dimers characterized by R²₂(10) graph-set motifs. These dimers further associate through N—H⋯O and C—H⋯O inter­actions, forming supra­molecular layers lying parallel to the (104) crystallographic plane. Aromatic π–π stacking inter­actions and C—H⋯π contacts contribute to the tri-periodic supra­molecular architecture.

Structure description

meta-Amino­benzoic acid has uses in organic synthesis, chemical biology, and materials science (Benke et al., 2020 ▸). It facilitates the formation of supra­molecular sheets, rendering it a valuable component for the design of peptide-based frameworks and amyloid-mimetic fibrillar architectures (Boruah & Roy, 2022 ▸). Its electron-rich aromatic framework and amino-substituted functionality promote the synthesis of a wide range of bioactive heterocycles, making it a valuable precursor in medicinal chemistry, agrochemical design and functional material development (Kundu et al., 2002 ▸; Maity et al., 2013 ▸; Dutta et al., 2023 ▸). As part of our studies in this area, we now describe the synthesis and structure of the title compound (Fig. 1 ▸).

Figure 1.

The mol­ecular structure of the title compound with displacement ellipsoids drawn at the 30% probability level.

The linking angle (C4—C5—N1—C9) between the aromatic ring (C3–C8) and the amide group (N1—C9=O3) is 170.99 (17)°, indicating near coplanarity. The amide–carbamate conformation, defined by atoms C5—N1—C9—O4 = 174.66 (16)°, indicates an extended transoid conformation. This conformation appears to facilitate optimal inter­molecular N—H⋯O hydrogen bonding. The torsion angle between the amide group and the Boc moiety (N1—C9—O4—C10) is 170.57 (14)°, with one of the C atoms of the tert-butyl group almost in the same plane as the amide group, one below and one above. Such behaviour is consistent with other Boc-protected aromatic amides reported in the Cambridge Structural Database (CSD; Groom et al., 2016 ▸), where Boc groups often adopt staggered conformations relative to the adjacent peptide or aryl systems to reduce unfavourable steric inter­actions. The ester group, defined by atoms O1—C2—C3—C8, exhibits a torsion angle of −173.73 (18)°, indicating an anti conformation.

In the extended structure, the mol­ecules are assembled into inversion dimers (Table 1 ▸, Fig. 2 ▸) through pairwise N—H⋯O and C—H⋯O hydrogen bonds, forming (10), (12) and (14) ring motifs that generate zigzag ribbons propagating along the c-axis direction (Fig. 3 ▸). An N—H⋯O hydrogen bond is observed between the carbamoyl and carboxyl­ate groups; additionally the ribbons are inter­connected by C—H⋯O hydrogen bonds, resulting in a double-chain architecture (Fig. 3 ▸). The twisting and non-coplanarity among the fragments appear to be a compromise between steric demands (particularly from the Boc group) and the desire for favourable inter­molecular inter­actions such as hydrogen bonds and stacking; additionally the ribbons are inter­connected by C—H⋯O hydrogen bonds, resulting in a double-chain architecture (Fig. 3 ▸).

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O1i	0.86	2.17	2.987 (2)	160
C4—H4⋯O1i	0.93	2.41	3.211 (2)	145
C13—H13C⋯O1ii	0.96	2.55	3.496 (3)	167

Symmetry codes: (i) ; (ii) .

Figure 2.

Partial packing of the title compound showing C—H⋯O and N—H⋯O hydrogen-bonded inversion dimers with (10), (12) and (14) graph-set motifs. The two independent mol­ecules are labelled as i and ii. [Symmetry codes: (i) 1 − x, 1 − y, 1 − z; (ii) 1 − x,  + y,  − z.]

Figure 3.

The crystal packing viewed approximately along [111] with the N—H⋯O and C—H⋯O hydrogen bonds shown as dashed lines.

Synthesis and crystallization

10 mmol (1.368 g) of meta-amino benzoic acid were dissolved in 10 ml of a 5% w/v sodium carbonate solution in a round-bottom flask. Subsequently, 12 mmol (2.619 g) of Boc-anhydride in 10 ml of dry tetra­hydro­furan (THF) were added. The resulting mixture, characterized by a pH of 12, was subjected to stirring for a duration of 12 h. The THF solvent was evaporated utilizing a rotavapor, and the resulting solution was adjusted to a pH of 2 using 2 N HCl. Upon three extractions with ethyl acetate, the organic layer underwent drying with anhydrous sodium sulfate and subsequent evaporation, resulting in a yield of 3.85 g (91%). In an ice bath, a combination of 20 ml of anhydrous methanol and 6 ml of thionyl chloride was prepared, followed by the addition of 20 ml (1.50 g) of the Boc-protected amino acid. The sealed flask was left to stir overnigh. Methanol was then removed through distillation and diethyl ether was introduced, yielding 1.32 g (89%) of the title compound. The purification process encompassed the utilization of silica gel along with a mixture of ethyl acetate and petroleum ether. The final products appeared as a white, colourless powder. Crystallization was accomplished by the gradual evaporation of mixed ethanol–water solvents, leading to the formation of stable, colourless crystals.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸.

Table 2. Experimental details.

Crystal data
Chemical formula	C13H17NO4
M r	251.28
Crystal system, space group	Monoclinic, P21/c
Temperature (K)	296
a, b, c (Å)	10.944 (3), 11.234 (3), 11.377 (3)
β (°)	112.481 (4)
V (Å3)	1292.5 (5)
Z	4
Radiation type	Mo Kα
μ (mm−1)	0.10
Crystal size (mm)	0.21 × 0.19 × 0.18
Data collection
Diffractometer	Bruker SMART APEXII CCD
Absorption correction	Multi-scan (SADABS; Krause et al., 2015 ▸)
Tmin, Tmax	0.631, 0.746
No. of measured, independent and observed [I > 2σ(I)] reflections	17731, 3220, 1966
R int	0.075
(sin θ/λ)max (Å−1)	0.668
Refinement
R[F2 > 2σ(F2)], wR(F2), S	0.050, 0.121, 1.01
No. of reflections	3220
No. of parameters	168
H-atom treatment	H-atom parameters constrained
Δρmax, Δρmin (e Å−3)	0.25, −0.24

Computer programs: APEX2 and SAINT(Bruker, 2008 ▸), SHELXS97 (Sheldrick, 2008 ▸), SHELXL2019/2 (Sheldrick, 2015 ▸), ORTEP-3 for Windows (Farrugia, 2012 ▸) and publCIF (Westrip, 2010 ▸).

Supplementary Material

CCDC reference: 2360910

Additional supporting information: crystallographic information; 3D view; checkCIF report

full crystallographic data

Methyl 3-[(tert-butoxycarbonyl)amino]benzoate. Crystal data

C13H17NO4	F(000) = 752
Mr = 251.28	Dx = 1.291 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 10.944 (3) Å	Cell parameters from 1967 reflections
b = 11.234 (3) Å	θ = 2.0–28.4°
c = 11.377 (3) Å	µ = 0.10 mm−1
β = 112.481 (4)°	T = 296 K
V = 1292.5 (5) Å3	Block, colourless
Z = 4	0.21 × 0.19 × 0.18 mm

Methyl 3-[(tert-butoxycarbonyl)amino]benzoate. Data collection

Bruker SMART APEXII CCD diffractometer	1966 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.075
ω and φ scans	θmax = 28.4°, θmin = 2.0°
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	h = −14→12
Tmin = 0.631, Tmax = 0.746	k = −14→14
17731 measured reflections	l = −15→15
3220 independent reflections

Methyl 3-[(tert-butoxycarbonyl)amino]benzoate. Refinement

Refinement on F2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F2 > 2σ(F2)] = 0.050	w = 1/[σ2(Fo2) + (0.0491P)2 + 0.2412P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.121	(Δ/σ)max < 0.001
S = 1.01	Δρmax = 0.25 e Å−3
3220 reflections	Δρmin = −0.23 e Å−3
168 parameters	Extinction correction: SHELXL-2019/2 (Sheldrick 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 restraints	Extinction coefficient: 0.0096 (15)
Primary atom site location: structure-invariant direct methods

Methyl 3-[(tert-butoxycarbonyl)amino]benzoate. Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. N and C-bound H atoms were positioned geometrically (C–H = 0.93–0.98 Å) and allowed to ride on their parent atoms, with Uiso(H) = 1.5Ueq(C) for methyl H atoms and 1.2Ueq(C) for all other H atoms.

Methyl 3-[(tert-butoxycarbonyl)amino]benzoate. Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
C1	0.62827 (18)	0.10342 (16)	0.47993 (18)	0.0243 (4)
H1A	0.583451	0.121193	0.391158	0.036*
H1B	0.643567	0.019253	0.490723	0.036*
H1C	0.711362	0.144702	0.512517	0.036*
C2	0.52600 (17)	0.25857 (15)	0.54767 (17)	0.0186 (4)
C3	0.43796 (17)	0.29156 (15)	0.61424 (16)	0.0183 (4)
C4	0.39765 (17)	0.40983 (16)	0.60627 (17)	0.0199 (4)
H4	0.426532	0.463943	0.560604	0.024*
C5	0.31466 (17)	0.44819 (15)	0.66576 (16)	0.0196 (4)
C6	0.27334 (18)	0.36633 (16)	0.73476 (17)	0.0216 (4)
H6	0.218801	0.390662	0.775977	0.026*
C7	0.31357 (18)	0.24816 (16)	0.74209 (17)	0.0230 (4)
H7	0.284882	0.194009	0.787865	0.028*
C8	0.39548 (18)	0.20972 (16)	0.68254 (17)	0.0212 (4)
H8	0.421773	0.130509	0.687994	0.025*
C9	0.18725 (18)	0.62189 (16)	0.69033 (17)	0.0216 (4)
C10	0.08789 (18)	0.81923 (16)	0.68615 (18)	0.0239 (4)
C11	−0.0445 (2)	0.7864 (2)	0.58521 (19)	0.0373 (6)
H11A	−0.037471	0.783865	0.503700	0.056*
H11B	−0.109167	0.844840	0.583632	0.056*
H11C	−0.071121	0.709729	0.604166	0.056*
C12	0.1331 (2)	0.94171 (18)	0.6618 (2)	0.0420 (6)
H12A	0.221113	0.956535	0.722260	0.063*
H12B	0.074302	1.001277	0.670662	0.063*
H12C	0.132422	0.944532	0.577242	0.063*
C13	0.0882 (2)	0.81423 (17)	0.81919 (18)	0.0284 (5)
H13A	0.055317	0.738297	0.832519	0.043*
H13B	0.032576	0.876232	0.829252	0.043*
H13C	0.176745	0.824988	0.880178	0.043*
N1	0.27956 (14)	0.56926 (13)	0.65412 (14)	0.0209 (4)
H1	0.320586	0.614865	0.620673	0.025*
O1	0.57322 (13)	0.32966 (11)	0.49628 (12)	0.0249 (3)
O2	0.54760 (12)	0.14127 (10)	0.54830 (12)	0.0227 (3)
O3	0.11464 (13)	0.57148 (11)	0.73180 (13)	0.0292 (3)
O4	0.19151 (12)	0.74073 (11)	0.67341 (12)	0.0243 (3)

Methyl 3-[(tert-butoxycarbonyl)amino]benzoate. Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
C1	0.0260 (10)	0.0196 (10)	0.0315 (11)	0.0011 (8)	0.0157 (9)	−0.0032 (8)
C2	0.0199 (9)	0.0145 (9)	0.0196 (10)	−0.0001 (7)	0.0056 (8)	0.0002 (7)
C3	0.0208 (9)	0.0168 (9)	0.0176 (9)	−0.0020 (7)	0.0075 (8)	−0.0011 (7)
C4	0.0223 (9)	0.0167 (9)	0.0208 (10)	−0.0012 (7)	0.0085 (8)	0.0023 (7)
C5	0.0198 (9)	0.0179 (9)	0.0201 (10)	−0.0015 (7)	0.0067 (8)	−0.0010 (7)
C6	0.0214 (10)	0.0216 (10)	0.0237 (10)	−0.0010 (8)	0.0109 (8)	−0.0019 (8)
C7	0.0285 (10)	0.0193 (10)	0.0228 (10)	−0.0032 (8)	0.0114 (8)	0.0021 (8)
C8	0.0259 (10)	0.0143 (9)	0.0229 (10)	−0.0004 (8)	0.0091 (8)	0.0000 (8)
C9	0.0237 (10)	0.0189 (9)	0.0219 (10)	0.0002 (8)	0.0085 (8)	−0.0011 (8)
C10	0.0251 (10)	0.0221 (10)	0.0294 (11)	0.0088 (8)	0.0157 (9)	0.0024 (8)
C11	0.0312 (12)	0.0526 (15)	0.0273 (12)	0.0144 (10)	0.0102 (10)	−0.0005 (10)
C12	0.0519 (14)	0.0235 (11)	0.0660 (16)	0.0143 (10)	0.0397 (13)	0.0107 (11)
C13	0.0308 (11)	0.0268 (11)	0.0271 (11)	0.0097 (9)	0.0107 (9)	−0.0003 (9)
N1	0.0232 (8)	0.0166 (8)	0.0279 (9)	0.0004 (6)	0.0153 (7)	0.0021 (6)
O1	0.0309 (8)	0.0182 (7)	0.0320 (8)	0.0013 (6)	0.0193 (6)	0.0026 (6)
O2	0.0301 (7)	0.0150 (7)	0.0279 (7)	−0.0001 (5)	0.0166 (6)	−0.0018 (5)
O3	0.0321 (8)	0.0212 (7)	0.0433 (9)	−0.0006 (6)	0.0246 (7)	−0.0010 (6)
O4	0.0274 (7)	0.0163 (7)	0.0349 (8)	0.0040 (5)	0.0183 (6)	0.0027 (6)

Methyl 3-[(tert-butoxycarbonyl)amino]benzoate. Geometric parameters (Å, º)

C1—O2	1.446 (2)	C9—O3	1.209 (2)
C1—H1A	0.9600	C9—O4	1.352 (2)
C1—H1B	0.9600	C9—N1	1.363 (2)
C1—H1C	0.9600	C10—O4	1.487 (2)
C2—O1	1.216 (2)	C10—C11	1.511 (3)
C2—O2	1.338 (2)	C10—C13	1.514 (3)
C2—C3	1.482 (2)	C10—C12	1.523 (3)
C3—C4	1.392 (2)	C11—H11A	0.9600
C3—C8	1.393 (2)	C11—H11B	0.9600
C4—C5	1.392 (2)	C11—H11C	0.9600
C4—H4	0.9300	C12—H12A	0.9600
C5—C6	1.392 (2)	C12—H12B	0.9600
C5—N1	1.406 (2)	C12—H12C	0.9600
C6—C7	1.391 (3)	C13—H13A	0.9600
C6—H6	0.9300	C13—H13B	0.9600
C7—C8	1.383 (2)	C13—H13C	0.9600
C7—H7	0.9300	N1—H1	0.8600
C8—H8	0.9300
O2—C1—H1A	109.5	O4—C10—C11	109.09 (15)
O2—C1—H1B	109.5	O4—C10—C13	111.44 (15)
H1A—C1—H1B	109.5	C11—C10—C13	112.67 (17)
O2—C1—H1C	109.5	O4—C10—C12	101.85 (14)
H1A—C1—H1C	109.5	C11—C10—C12	111.49 (17)
H1B—C1—H1C	109.5	C13—C10—C12	109.80 (17)
O1—C2—O2	122.88 (16)	C10—C11—H11A	109.5
O1—C2—C3	124.08 (16)	C10—C11—H11B	109.5
O2—C2—C3	113.04 (15)	H11A—C11—H11B	109.5
C4—C3—C8	120.08 (16)	C10—C11—H11C	109.5
C4—C3—C2	117.20 (16)	H11A—C11—H11C	109.5
C8—C3—C2	122.72 (16)	H11B—C11—H11C	109.5
C3—C4—C5	120.87 (16)	C10—C12—H12A	109.5
C3—C4—H4	119.6	C10—C12—H12B	109.5
C5—C4—H4	119.6	H12A—C12—H12B	109.5
C6—C5—C4	118.86 (17)	C10—C12—H12C	109.5
C6—C5—N1	123.80 (16)	H12A—C12—H12C	109.5
C4—C5—N1	117.34 (16)	H12B—C12—H12C	109.5
C7—C6—C5	120.04 (17)	C10—C13—H13A	109.5
C7—C6—H6	120.0	C10—C13—H13B	109.5
C5—C6—H6	120.0	H13A—C13—H13B	109.5
C8—C7—C6	121.20 (17)	C10—C13—H13C	109.5
C8—C7—H7	119.4	H13A—C13—H13C	109.5
C6—C7—H7	119.4	H13B—C13—H13C	109.5
C7—C8—C3	118.95 (17)	C9—N1—C5	126.77 (15)
C7—C8—H8	120.5	C9—N1—H1	116.6
C3—C8—H8	120.5	C5—N1—H1	116.6
O3—C9—O4	125.57 (16)	C2—O2—C1	115.44 (14)
O3—C9—N1	126.05 (17)	C9—O4—C10	120.18 (13)
O4—C9—N1	108.38 (15)
O1—C2—C3—C4	6.4 (3)	C2—C3—C8—C7	179.86 (16)
O2—C2—C3—C4	−172.91 (15)	O3—C9—N1—C5	−4.7 (3)
O1—C2—C3—C8	−173.73 (18)	O4—C9—N1—C5	174.66 (16)
O2—C2—C3—C8	7.0 (2)	C6—C5—N1—C9	−10.3 (3)
C8—C3—C4—C5	−0.1 (3)	C4—C5—N1—C9	170.99 (17)
C2—C3—C4—C5	179.82 (16)	O1—C2—O2—C1	−1.8 (2)
C3—C4—C5—C6	0.6 (3)	C3—C2—O2—C1	177.44 (15)
C3—C4—C5—N1	179.40 (16)	O3—C9—O4—C10	−10.1 (3)
C4—C5—C6—C7	−0.8 (3)	N1—C9—O4—C10	170.57 (14)
N1—C5—C6—C7	−179.51 (17)	C11—C10—O4—C9	−62.9 (2)
C5—C6—C7—C8	0.5 (3)	C13—C10—O4—C9	62.1 (2)
C6—C7—C8—C3	0.0 (3)	C12—C10—O4—C9	179.17 (16)
C4—C3—C8—C7	−0.2 (3)

Methyl 3-[(tert-butoxycarbonyl)amino]benzoate. Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1i	0.86	2.17	2.987 (2)	160
C4—H4···O1i	0.93	2.41	3.211 (2)	145
C13—H13C···O1ii	0.96	2.55	3.496 (3)	167

Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) −x+1, y+1/2, −z+3/2.

Funding Statement

Funding for this research was provided by: Science and Engineering Research Board (grant No. EMR/2017/000420 to K. M. P. Raja; grant No. EEQ/2018/001290 to K. M. P. Raja); Department of Biotechnology, Ministry of Science and Technology, India (grant No. BT/PR40237/BTIS/137/79/2023 to K. M. P. Raja).