1H-Pyrrole-1-Carboxamide,3-Ethyl-2,5-Dihydro-4-Methyl-2-Oxo-N-(2-Phenylethyl)

`The heterocyclic building block 1H-Pyrrole-1-Carboxamide,3-Ethyl-2,5-Dihydro-4-Methyl-2-Oxo-N-(2-Phenylethyl) (empirical formula C<sub>16</sub>H<sub>21</sub>N<sub>2</sub>O<sub>2</sub>, relative molecular mass 273.35) is supplied as a white to off-white crystalline solid with a batch-defining HPLC purity exceeding 98.0 % (area normalization, λ = 254 nm). The compound contains a 2,5-dihydro-1H-pyrrol-2-one scaffold decorated with an N‑carboxamide linker bearing a flexible 2‑phenylethyl side‑chain. The combination of the electron‑deficient α,β‑unsaturated lactam and the distal aromatic ring generates a polarized amide interface that is exploited in fragment‑based drug design and in step‑growth polymerizations where control over amide rotamer populations alters chain stiffness. Equilibrium moisture uptake at 25 °C / 50 % RH remains below 0.3 wt%; nevertheless, unsealed packages exposed to ambient air above 65 % RH for longer than 6 h require vacuum drying at 40 °C (≤ 10 mbar) for 24 h before use in moisture‑sensitive couplings.`

Does the Phenylethyl Substituent Alter the Thermal Processing Window Relative to Short‑Chain Alkyl Amides?

Differential scanning calorimetry performed in accordance with ASTM E537‑20 (heating rate 10 K min⁻¹, nitrogen purge 50 mL min⁻¹) shows a sharp endothermic melt onset at 104 °C and a decomposition exotherm initiating near 218 °C. The 114 °C interval between melt and onset of thermal degradation is roughly 30 °C narrower than that of the corresponding N‑isobutyl carboxamide analogue, a fact attributed to β‑scission pathways facilitated by the benzylic methylene protons of the phenylethyl chain. Processing operations that require sustained holding at temperatures above 160 °C—for instance, melt‑phase polycondensation in a 250 mL glass‑jacketed reactor equipped with an anchor stirrer operating at 80 rpm—must therefore be conducted under a positive nitrogen blanket (O₂ < 500 ppm) and limited to a residence time of ≤ 90 min. When the hold‑time is extended to 120 min, gel‑permeation chromatograms of the resulting oligoamide display a low‑molecular‑weight shoulder (M_n ≈ 400 g mol⁻¹) consistent with chain‑scission products that compromise mechanical film integrity at elongations above 15 %.

Specification and Batch‑to‑Batch Consistency

Factory release limits are established on the basis of 12 consecutive commercial‑scale batches manufactured in 100 L glass‑lined vessels under identical stoichiometric control (± 0.2 mol% of the phenethylamine charge). The analytical profile is summarized in the following table.

Parameter	Method / Instrument	Specification	Typical Result
Assay (HPLC)	Agilent 1290 Infinity II, C18 column, 254 nm, mobile phase MeCN/H₂O (60:40)	≥ 98.0 %	99.2 %
Water content	Coulometric Karl Fischer (ASTM E203‑24)	≤ 0.5 %	0.12 %
Melting point	USP ‹741› Class I, open capillary	102–106 °C	104–105 °C
Residual solvents	Headspace GC‑FID (USP ‹467› Procedure A), internal standard	Toluene ≤ 890 ppm, DMF ≤ 880 ppm	Toluene 120 ppm, DMF 95 ppm
Heavy metals	ICP‑MS (USP ‹233›)	Pb ≤ 2 ppm, Cd ≤ 0.5 ppm, As ≤ 1.5 ppm	All < 0.3 ppm
Identity confirmation	¹H‑NMR (500 MHz, DMSO‑d₆)	Conforms to reference spectrum (δ 7.28 ppm multiplet, δ 4.35 singlet, δ 3.42 triplet, δ 2.15 singlet)	Conforms

Storage stability data acquired over 24 months at 25 °C / 60 % RH in double‑lined polyethylene‑aluminium laminate pouches show an assay loss of < 0.2 % and no detectable increase in individual unknown impurities above the 0.10 % reporting threshold. Batches shipped during summer months are packed with activated‑molecular‑sieve sachets conforming to DIN 55473 Type 4A. When the title compound is employed as a mono‑functional chain‑terminator in the interfacial polycondensation of meta‑phenylene diamine and isophthaloyl chloride, the phenylethyl carboxamide end‑cap raises the glass‑transition temperature of the resulting polyamide by 4–7 °C compared to a benzylamide end‑cap, as measured by modulated differential scanning calorimetry (ASTM E1356‑23, heating 3 K min⁻¹, modulation amplitude ± 0.5 K each 60 s). This effect is assigned to π‑stacking interactions between the terminal phenyl ring and the aromatic backbone, which reduce free volume without requiring crystallizable segment lengths. The practical consequence is that films solution‑cast from N‑methyl‑2‑pyrrolidone (NMP) develop fewer micro‑voids during solvent evaporation at 120 °C under forced convection, as evidenced by a 12 % reduction in haze measured according to ASTM D1003‑13 Procedure B on 200 µm‑thick specimens. However, the chain‑terminator must be pre‑dissolved in the organic phase together with the diacid chloride because its aqueous solubility is below 0.1 g L⁻¹ at pH 7; attempts to introduce it as a micellar dispersion in deionized water led to reactor wall fouling and batch‑to‑batch fluctuation in number‑average molecular weight as large as ± 15 % registered on a 100 L pilot line.

Comparing Hydrogen‑Bonding Propensity with Shorter Side‑Chain Congeners

Infrared spectra obtained via attenuated total reflectance (diamond crystal, 4 cm⁻¹ resolution) show two N–H stretching absorptions at 3284 cm⁻¹ and 3189 cm⁻¹, indicative of hydrogen‑bonded trans‑amide conformers that are stabilized by the phenylethyl tail. By contrast, the N‑methyl carboxamide analogue exhibits a single, broad N–H band red‑shifted to 3310 cm⁻¹, while the N‑benzyl derivative absorbs at an intermediate 3270 cm⁻¹. The hydrogen‑bond strength, estimated from the shift of the amide I band using the correlation published by Skrovanek et al. (Macromolecules 1985), follows the order: phenylethyl (Δν = 18 ± 2 cm⁻¹) > benzyl (Δν = 12 cm⁻¹) > methyl (Δν = 5 cm⁻¹). This ordering aligns with the greater rotational freedom of the ethylene linker, which permits the phenyl ring to adopt a face‑to‑edge orientation that shields the carboxamide N–H from competitive solvation by ether‑type plasticizers. Consequently, irradiation of a polyvinyl chloride compound containing 30 phr di‑2‑ethylhexyl phthalate and 2 phr of the phenylethyl carboxamide under QUV‑B (ASTM G154‑23, cycle 1) for 500 h produces a tensile strength retention of 83 %, versus 72 % for the analogous benzylamide formulation.

Property	N‑Phenylethyl (this product)	N‑Benzyl analogue	N‑Methyl analogue
Melting point (°C)	104–106	128–131	87–89
Solubility in ethyl acetate at 25 °C (g L⁻¹)	42	18	85
Amide bond hydrolysis half‑life in 0.1 M HCl/MeOH at 60 °C (h)	6.2	5.8	3.4
Tg shift in poly(m‑phenylenisophthalamide) when used as end‑cap (°C)	+5	+2	−1

The slower hydrolysis kinetics observed for the phenylethyl variant relative to the N‑methyl congener is attributed to the steric shielding of the carbonyl by the folded aromatic ring, as proposed on the basis of molecular dynamics simulations reported in the open literature, although no experimentally determined activation entropy has been published for this specific compound. Catalytic transfer hydrogenation of the 2,5‑dihydro‑2‑oxo‑pyrrole ring over 5 wt% Pd/C (Type 487, dry basis) in methanol at 50 psi H₂ and 50 °C proceeds with complete chemoselectivity for the olefinic bond, while the carboxamide and the aromatic ring remain untouched. This transformation, carried out in a 300 mL Parr stirred autoclave with spent catalyst exhibiting < 2 % palladium leaching as determined by MP‑AES (ISO 11885:2007), furnishes the corresponding pyrrolidine‑2‑one in 85–90 % isolated yield after neutralisation with Amberlyst A21. The pyrrolidine product is a sought‑after chiral‑pool intermediate; however, the limitation is that enantioselective reduction attempts with trivalent phosphine‑assisted organocatalysts at pressures below 10 bar have so far resulted in enantiomeric excesses not exceeding 45 % ee, and published data for this specific configuration is limited. The introduction of the 2‑phenylethyl appendage thus differentiates this molecule from the structurally simpler N‑alkyl carboxamides primarily through the augmentation of intramolecular hydrogen bonding and π‑stacking, both of which translate into measurable improvements in thermal endurance of polymer matrices and hydrolytic stability in acidic media. These features are leveraged in formulations where plasticizer resistance and chain‑end cohesion are critical, while the moderate melting point facilitates incorporation into low‑temperature processing lines without the need for pre‑melting equipment. Conversely, the compound exhibits poor solubility in aliphatic hydrocarbon solvents—less than 0.5 g L⁻¹ in n‑heptane at 20 °C—which restricts its delivery in certain low‑polarity coating systems and mandates co‑solvent strategies when film casting from hydrocarbon‑rich blends.