Phenoxyacetyl Chloride Research Articles

Linear Free Energy Analysis on the Ring‐Expansion of Arylthiiranes with Ketenes

AbstractThe ring‐expansion of arylthiiranes and phenoxyacetyl chloride was performed in the presence of triethylamine and provided a novel strategy for the synthesis of 4,5‐dihydrobenzo[d]thiepin‐2(1H)‐ones, benzo[d]‐ϵ‐thiolactones, directly without catalysts or additives. Its linear free energy analysis was conducted on the basis of competitive experiments. The results indicate that both reaction constants are close to zero (0.14 for σm and 0.20 for σp), supporting the proposed sulfur‐shifted ene mechanism. The current reaction features atom and step‐economic one‐pot characteristic via a tandem sequence of in situ ketene generation, sulfur‐shifted ene reaction, and aromatization.

Stereoselective Synthesis of Novel Monocyclic cis‐β‐Lactams Bearing 1,3,4‐Thiadiazole Nucleus: Bioactive Agents and Potential Synthons

AbstractA simple and efficient procedure for the stereoselective synthesis of novel monocyclic cis‐β‐lactams, pharmaceutically fascinating and potential synthons have been developed. The reaction of ketene derived insitu from phenoxyacetyl chloride with tetralone substituted imines resulted in the exclusive formation of monocyclic cis‐β‐lactams containing 1,3,4‐thiadiazole nucleus by [2+2] cycloaddition reaction. The structures of all the novel synthesized monocyclic cis‐β‐lactams were verified using various spectroscopic techniques such as FT‐IR, 1H NMR, 13C NMR, HRMS, and elemental analysis (CHN). The cis configuration of β‐lactams was deduced using the coupling constant (J) value of H‐3 and H‐4. The prominent features of this work are simple reaction conditions, good yields, easy isolation of products, and no column chromatography separation. All products were obtained by a simple crystallization technique.

SYNTHESIS, IN SILICO STUDIES AND EVALUATION OF ANTIBACTERIAL ACTIVITY OF 4-SUBSTITUTED BENZYLIDENE-2-(PHENOXYMETHYL) OXAZOL-5(4H)-ONES

Objective: Arylidene-1, 3-oxazol-5-ones represent potential antibacterial agents. In the present work, a series of 4-substituted benzylidene-2- (phenoxymethyl) oxazol-5(4H)-ones were synthesized and screened for antibacterial activity against Gram-negative bacteria Escherichia coli. To explore plausible mechanisms, synthesized compounds were docked with DNA-Gyrase enzyme.
 Methods: All the reactants, phenoxy acetyl chloride, acetic anhydride, sodium acetate, substituted aromatic aldehydes, and glycine were triturated in a mortar by mechanical stirring. The antibacterial potentiality of the compounds was screened against E. coli using the disk diffusion method and the activity was recorded as a zone of inhibition.
 Results: Compound 2d, possessing 3, 4, 5-trimethoxy functionality on benzylidene ring exhibited the highest activity with 19 mm of the zone of inhibition which might be due to its higher interactions with DNA-Gyrase enzyme (ΔG-8.41 kcal/mol). Compounds 2a, 2b, and 2c exhibited moderate activity in the antimicrobial assay as well as in docking study indicating the positive contribution of substitution on benzylidene ring.
 Conclusion: A series of 4-substituted benzylidene-2-(phenoxymethyl) oxazol-5(4H)-ones were synthesized and evaluated for antibacterial activity. Compounds 2a, 2b, and 2c displayed moderate activity whereas 2d showed maximum zone of inhibition (19 mm). The good activity of these derivatives presumed to be due to the conformational flexibility of phenoxy methylene moiety which can be well accommodated in the target binding site.

Synthesis, Crystal Structure and Biological Activity of Novel N‐substituted Diazabicyclo Derivatives

A series of N‐substituted diazabicyclo derivatives were designed and synthesized based on the active subunit combination and structure–activity relationship theory. The compounds were prepared by levulinic acid or ester with diamine, then acylation with phenoxy acetyl chloride or acetoxy acetyl chloride. All the structures were characterized by IR, 1H NMR, 13C NMR, MS, and elemental analysis. The single crystal of compound 4a was determined by X‐ray crystallography. The preliminary bioassay showed that all products could protect soybean against injury caused by 2,4‐D butylate to some extent.

Synthesis and herbicidal activity of optically active α-(substituted phenoxyacetoxy) (substituted phenyl) methylphosphonates

α-(Substituted phenoxyacetoxy) alkylphosphonates containing one chiral carbon atom have been demonstrated to be PDHc inhibitor with good herbicidal activity and some of them could be used as potential herbicide. In order to determine any difference in herbicidal activities between (R) and (S) isomers, the synthetic method of optically active substituted phenylalkylphosphonates IB were explored. A highly practical, enantioselective hydrophosphonylation was developed to prepare optically active O,O-dimethyl α-hydroxyalkylphosphonates 3 as key intermediate by asymmetric addition reaction of dimethylphosphite 1 and several kinds of aldehydes 2 using tridentate Schiff base Al(III) complexes as catalysts. A series of novel O,O-dimethyl α-(substituted phenoxyacetoxy)(substituted phenyl)methylphosphonates IB including (R) and (S) enantiomers were further synthesized with excellent enantioselectivity (95–99% ee) by the condensation of optically active α-hydroxyl (substituted phenyl)methylphosphonates 3 and substituted phenoxyacetyl chlorides 4. The herbicidal activities of title compound IB including their racemates, (R) and (S) enantiomers were evaluated in greenhouse for post-emergence application. All compounds IB showed significant inhibitory activity against dicotyledonous plants. A difference in herbicidal effect among racemate, (R) and (S) enantiomers were observed. Especially IB7 and IB10 showed obvious chiral selectivity in inhibitory activity against chickweed. (S)-IB7 with ED50 of 22.8gai/ha was found to be most effective enantiomer against chickweed and its inhibitory activity was 8.17 times higher than (R)-IB7. (S)-IB7 as potential herbicide would be effective at lower rates than (R)-IB7 or (rac)-IB7.

Synthesis and Antimicrobial Activity of Novel 2‐Substituted Phenoxy‐N‐(4‐substituted Phenyl‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazol‐2‐yl)acetamide Derivatives

A series of 2‐substituted phenoxy‐N‐(4‐substituted phenyl‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazole‐2‐yl)acetamide derivatives 8a, 8b, 8c, 8d, 8e, 8f, 8g, 8h, 8i, 8j, 8k, 8l, 8m, 8n, 8o, 8p, 8q, 8r, 8s, 8t was synthesized by the reaction of phenoxyacetyl chloride 7 with intermediate 4‐substituted phenyl‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazol‐2‐amine 5. Their structures were confirmed by 1H NMR, 13C NMR, MS, IR, and elemental analyses. The synthesized compounds were also screened for their antimicrobial activity against three types of plant fungi (Gibberella zeae, Phytophthora infestans, and Paralepetopsis sasakii) and two kinds of bacteria [Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac)] showing promising results. In particular, 8b, 8f, 8g, and 8h exhibited excellent antibacterial activity against Xoo, with 50% effective concentration (EC50) values of 35.2, 80.1, 62.5, and 82.1 µg/mL, respectively, which are superior to the commercial antibacterial agent bismerthiazol (89.9 µg/mL). The preliminary structure–activity relationship studies of these compounds are also briefly described.

One‐pot Synthesis, Crystal structure, and Bioactivity of N‐Phenoxyacetyl‐2,4,5‐trisubstituted‐1,3‐oxazolidines

N‐phenoxyacetyl‐1,3‐oxazolidine derivatives were synthesized by the cyclization and acylation with β‐amino alcohol, ketone, and phenoxyacetyl chloride as the starting materials. All compounds were characterized by IR, 1H NMR, 13C NMR, ESI‐MS, and elemental analysis. The configuration of 4a was determined by X‐ray crystallography. The preliminary biological tests showed that all products could protect soybean against injury caused by 2,4‐D butylate to some extent.

Synthesis of nucleosides containing a photolabile 2-(2-nitrophenyl)propoxycarbonyl group

At present, DNA biochips are widely used in medicine as diagnostic systems [1, 2]. Oligonucleotide biochips are often obtained with the aid of photolabile protecting groups [3–7]. The latter should be stable under the conditions of oligonucleotide synthesis but should be readily removed by photolysis without involving the protected moiety. A widely used photolabile protecting group is the o-nitrobenzyl group [3, 8–10]. The goal of the present work was to extend the series of nucleosides protected by the photolabile 2-(2-nitrophenyl)propoxycarbonyl group and containing readily removable protecting groups in the aromatic heteroring, which can subsequently be used in the design of oligonucleotide biochips. We have synthesized previously unknown nucleosides 4–7. Compounds 4 and 5 were obtained by acylation of 2′-deoxyguanosine and 2′-deoxyadenosine with phenoxyacetyl chlorides 1 and 2, respectively. Nucleosides 6 and 7 protected by photolabile 2-(2-nitrophenyl)propoxycarbonyl groups were synthesized by treatment of compounds 4 and 5, respectively, with 2-(2-nitrophenyl)propyl chloroformate (3) which was prepared as described in [10]. Compounds 6 and 7 were isolated as mixtures of diastereoisomers. ISSN 1070-4280, Russian Journal of Organic Chemistry, 2015, Vol. 51, No. 1, pp. 141–144. © Pleiades Publishing, Ltd., 2015. Original Russian Text © E.B. Nikolaenkova, I.A. Os’kina, V.A. Savel’ev, A.Ya. Tikhonov, V.A. Ryabinin, A.N. Sinyakov, 2015, published in Zhurnal Organicheskoi Khimii, 2015, Vol. 51, No. 1, pp. 142–144.

Synthesis of Novel Tricyclic 1,5‐Benzothiazepine Derivatives Bearing Quinoline Moiety via [2 + 2] Cycloaddition Reaction

A series of new tricyclic 1,5‐benzothiazepine derivatives were synthesized by the reaction of 1,5‐benzothiazepine containing 2‐phenoxy‐quinoline with chloracetyl chloride and phenoxyacetyl chloride. The structures of the target compounds were confirmed by IR, 1H NMR MS, and elemental analysis.

Synthesis and Antimicrobial Evaluation of Novel Bis-β-lactam Grafted Macrocycles

A series of macrocyclic bis-β-lactams has been synthesized in three good yielding steps using a Staudinger [2+2] cycloaddition reaction of ketene derived from phenoxyacetyl chloride as the key step. The reaction provided a diastereomeric mixture of cis-anti-cis (C2-symmetry) and cis-syn-cis (meso) bis-β-lactam grafted macrocycles which were screened for their in vitro antibacterial and antifungal activities against four human pathogenic bacteria and two pathogenic fungi. Compounds 6a and 6b exhibited antibacterial activity at lower concentration against four bacterial pathogens and compounds 10b and 12a showed antifungal activity against two fungal pathogens when compared to reference control.

Synthesis of Some Prospective Bioactive Azeto[2,1-d][1,5]benzothiazepinones

Ten azeto[2,1-d][1,5]benzothiazepinone derivatives 6a–j were synthesized starting from 4-acetyl-2-phenyl-1,2,3-triazole 1. First, condensation of 1 with various aldehydes 2a–e afforded α,β-unsaturated carbonyl compounds 3a–e, which subsequently underwent cyclization with o-aminothiophenol to yield the corresponding 2,4-disubstituted-1,5-benzothiazepines 4a–e. Treatment of 4a–e with chloroacetyl chloride 5a or phenoxyacetyl chloride 5b by [2+2] cycloaddition reaction gave the title compounds 6a–j. The assignment of the structures of 6a–j was made by 1H NMR, MS, and elemental analyses.

Catalytic, asymmetric synthesis of α-phenoxy-β-aryl-β-lactams

The reactions of phenoxyacetyl chloride with aryl imines in the presence of catalytic quantities of a silyl cinchona alkaloid and an achiral Lewis acid affords α-phenoxy-β-aryl-β-lactams. These reactions presumably proceed by way of ketene or acyl ammonium enolate intermediates. These reactions occur in a high enantioselectivity regardless of the nature of the Lewis acid, however, a high diastereoselectivity depended on the use of a hindered lanthanide complex as the Lewis acidic co-catalyst.

A structurally diverse heterocyclic library: A benzothiazepine-fused ? -lactam library derived from reaction of 2,3-dihydro-1,5-benzothiazepines and acyl chlorides: Synthesis and stereochemistry

A 1H-azeto[2,1-d][1,5]benzothiazepin-1-one, beta-lactam derivatives of dihydrobenzothiazepines library derived from reactions of 2,4-disubstituted 2,3-dihydro-1,5-benzothiazepines and acyl chlorides, including phthalimidoacetyl chloride, chloroacetyl chloride, dichloroacetyl chloride and phenoxyacetyl chloride, was built up through parallel solution-phase synthesis. Stereochemistry of 1H-azeto[2,1-d][1,5]benzothiazepin-1-ones in the reaction process is discussed.

Transient silylation of the guanosine O6 and amino groups facilitates N-acylation.

[reaction: see text] The formation of a guanosine derivative silylated at both the O6 and amino groups was identified by (15)N NMR. This intermediate allows facile reaction with acetyl chloride or phenoxyacetyl chloride to give in high yield the corresponding N-protected guanosine derivatives, suitable for use in RNA synthesis. The acetyl and phenoxyacetyl amino protecting groups are, respectively, 4 and 230 times more labile than the isobutyryl group to methylamine/ethanol deprotection.

Stereospecific Synthesis of Azeto[2,1‐d][1,5]benzothiazepin/diazepin‐1‐ones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis and X‐Ray Crystallographic Analysis of 4,4′‐Disubstituted N‐(2‐Hydroxypropyl)azetidin‐2‐one from Benzil and (.+‐.)‐2‐Amino‐1‐methylethanol.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis and X-ray Crystallographic Analysis of 4,4′-Disubstituted N–(2-Hydroxypropyl)Azetidin-2-One from Benzil and (±)-2-Amino-1-Methylethanol

5,6-Dihydro-2-hydroxy-6-methyl-2,3-diphenyl-2 H-1,4-oxazine 1, derived from benzil and (±)-2-amino-1-methylethanol, reacts with phenoxyacetyl chloride in the presence of triethylamine to give a single isomer of a 4,4′-disubstituted azetidin-2-one 2, whose structure has been unambiguously confirmed by X-ray crystallographic analysis.

Stereospecific synthesis of azeto[2,1‐d]‐ [1,5]benzothiazepin/diazepin‐1‐ones

Abstract2a,4‐Disubstituted 2‐phenoxy‐2,2a,3,4‐tetrahydro‐1H‐azeto[2,1‐d][1,5]benzothiazepin‐1‐ones and 5‐benzoyl‐2‐phenoxy‐2a,3,4,5‐tetrahydro‐azeto[1, 2‐a][1,5]benzodiazepin‐1(2H)‐ones were synthesized in moderate to good yields by stereospecific Staudinger cycloaddition reactions of 2,4‐disubstituted 2,3‐dihydro‐1,5‐benzothiazepines and 1‐benzoyl‐2,3‐dihydro‐1H‐1,5‐benzodiazepines, respectively, with phenoxy acetyl chloride in the presence of triethylamine in anhydrous benzene. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:564–569, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10196

Alkyne-Co(2)(CO)(6) Complexes in the Synthesis of Fused Tricyclic beta-Lactam and Azetidine Systems(,)(1).

A synthetic approach to racemic and enantiomerically pure, fused tricyclic 2-azetidinones and azetidines has been developed by using a Pauson-Khand (P-K) reaction on monocyclic enyne-beta-lactams as the key synthetic step. The access to cyclization precursors, monocyclic beta-lactams 1-7, was achieved by Staüdinger reaction of enyne imines 8 and 9 and D-glyceraldehyde imines 10 and (benzyloxy)- or phenoxyacetyl chlorides. Enyne imines 8 and 9 formed cis-2-azetidinones 1 and 2 having the required enyne moiety. cis-2-Azetidinones 11 were obtained as single diastereomers and transformed to enyne-2-azetidinones 3 and 5 by standard methodology. Alternatively, 4-formyl-2-azetidinones 14 were prepared by cyclization of p-anisyl glyoxal diimine and (benzyloxy)acetyl chloride and converted to racemic enyne-beta-lactams 4 and 6 by standard reactions. Enyne-2-azetidinones 1-7 were reacted with Co(2)(CO)(8) to quantitatively yield the corresponding alkyne-Co(2)(CO)(6) complexes. Reaction of such complexes with different promoters, especially heat and TMANO, formed tricyclic 2-azetidinones 15-19 with the ring system fused to the C3-C4 and C4-N1 lactam bonds. Yields were usually high, and the processes were highly diastereoselective. The exceptions were enyne-2-azetidinones 2 and 3a bearing N-propargyl moieties. These products decomposed to mixtures of unidentifiable products. Inhibition of the amide resonance was postulated as responsible for the failure of beta-lactams 2 and 3a to form tricyclic systems. In fact, the analogous enyne-azetidines 20a,b smoothly cyclized to form the corresponding tricyclic systems. This approach to tricyclic azetidines was extended to prepare different products. A new, unprecedented, N1-C2 bond breakage was also observed in the azetidine ring. The results described show that the P-K reaction is a suitable approach to tricyclic 2-azetidinones and azetidines. These are the first examples reported for a P-K reaction in with the enyne system is tethered to a strained heterocyclic four-membered ring.

Reaction of 2-alkoxy-2-methylthio-5,6-dihydro-4H-1,3-thiazines with phenoxyacetyl chloride

The reaction of 4-alkoxytetrahydro-1, 3-thiazine-2-thiones with methyl iodide and subsequent treatment of the resultant S-alkylation products by suitable sodium alcoholates yielded 4-alkoxy-2-methylthio-S, 6-dihydro-4H-1, 3-thiazines, which upon reaction with phenoxyacetyl chloride in the presence of triethylamine was stereospecifically converted into 4-alkoxy-6-methylthio-7-phenoxvcephams.