Crystal structure of N-phenyl-3-[2-(4'-chlorophenylthio)propanoyl]-2- azetidinone, C18H16ClNO2S

Abstract

Source of materialTo a solution of N,O-dimethylhydroxylamine hydrochloride (2.00 g, 20.70 mmol) and pyridine (3.30 ml, 41.16 mmol) in 15.0 mL acetonitrile, at 273 K, a solution of 2-(4¢-chlorophenylthio)propanoyl chloride [1] (4.84 g, 20.58 mmol) in 5 mL acetonitrile was added slowly. The reaction mixture was allowed to reach room temperature and was stirred overnight. Then it was concentrated and poured into 0.2 N HCl (10.0 mL) solution, washed with water and three times extracted with chloroform. The combined extracts were dried over MgSO 4. After solvent evaporation the crude material was purified by chromatography on silica gel (chloroform), giving a viscous liquid of 2-(4¢-chlorophenylthio)-N-methoxy-Nmethylpropanamide ( 3.93 g, 14.40 mmol, 70 % yield). A solution of n-butyllithium (3.00 mL, 1.9 M in n-hexane) was added to isopropylamine (0.80 mL, 5.47 mmol) in THF (6.6 mL) at 195 K. It was then added a solution of N-phenyl-2-azetidinone (0.80 g, 5.47 mmol) in THF (4.6 mL) and stirred for 30 minutes at the same temperature. Then, a solution of 1.19 g (4.56 mmol) of 2-(4¢-chlorophenylthio)-N-methoxy-N-methylpropanamide in THF (2.0 mL) was added slowly. The reaction was monitored by TLC with chloroform/n-hexane (70 : 30) as eluent. The reaction mixture was poured into aqueous NH 4 Cl and extracted with chloroform (3×). The combined extracts were dried over MgSO 4. After solvent evaporation, the obtained amorphous white solid was recrystallized from methanol giving 1.30 g of the C1(R)C3(S)/C1(S)C3(R) diastereomer of the title compound (2.05 mmol, yield 45 %; m.p. 384-386 K). Crystals for X-ray analysis were obtained by vapor diffusion from chloroform/n-hexane at 278 K. Elemental analysis: found C, 62.73 %; H, 4.88 %; N, 4.37 %; calc. for C 18H16ClNO2S C, 62.51 %; H, 4.66 %; N, 4.05 %. Experimental detailsDue to the poor diffraction quality of the crystal, the number of observed reflections was low. H atoms were geometrically fixed to their parent ones and their displacement parameters calculated as 1.2U eq(C) or 1.5Ueq(C). DiscussionThe four-membered ring is planar within experimental accuracy (r.m.s. being 0.006 Å) and makes a dihedral angle of 6.6(3)°with the phenyl ring attached to it, which can be ascribed to the short C···O interaction: d(C14···O2) = 3.114 (

Stereochemical and electronic interaction studies of some N-methoxy-N-methyl-2-[(4′-substituted)phenylsulfinyl]propanamides

“…The N-methoxy-N-methyl-2- , were prepared as previously described [9,10]. As the title compounds present two stereogenic centers, i.e.…”

“…The pure sulfinylamides (1)-(4) are viscous liquids (a pair of diastereomers) which could not be resolved from chromatography on silica gel. The fractional crystallization of the amorphous yellow solid 4 0 -nitro-derivative (5) from chloroform/n-hexane affords initially the racemic mixture of C R S S /C S S R diastereomer (mp 94-97°C), followed by the racemic mixture of C R S R /C S S S diastereomer (mp 117-119°C) [10] in ca. 8:2 ratio.…”

“…Suitable crystals for X-ray analysis of the C R S S /C S S R and C R S R /C S S S diastereomer pairs were obtained by vapour diffusion from chloroform/n-hexane at 5°C. As the crystal structure of the C R S R /C S S S diastereomer pair was already described [10] …”

“…The parent N-methoxy-N-methylpropanamide (6) was computed at the HF/6-31G ** level and the geometry of its anti conformer was used as the starting point to determine the preferred conformations for 3. For the C R S S /C R S R diastereomers of 3, all the possible cis and gauche orientations of the C-S bond with respect to the carbonyl group were fully optimized, allowing complete relaxation of all internal parameters.…”

“…N-Methoxy-N-methylamides (Weinreb amides) are important acylating agents which have been widely used for preparation of ketones [2][3][4]. The efficiency of this reaction allowed us to synthesise some acyl derivatives of b-lactams in good yields, which was not possible through traditional methods employing other carboxylic acid derivatives [5][6][7]. A comparison between the energies of some relevant orbitals (computed by HF/6-31G ** ) of the N,N-diethylacetamide (a) [1] with those of the N-methoxy-N-methyl-acetamide (b) (present work) (data in Fig.…”