Benzyl Chloromethyl Research Articles

Condensation of substituted benzaldehydes with benzyl chloromethyl ether at the phase transfer catalysis

Condensation of substituted benzaldehydes with benzyl chloromethyl ether at the phase transfer catalysis

Preparation, swelling properties, and displacement performance of functional amphiphilic microspheres

ABSTRACTBecause polymers containing benzyl chloromethyl groups are easily modified for functional production, the dispersion polymerization of acrylamide, 4‐vinylbenzyl chloride, and N,N‐methylene bisacrylamide in dimethylformamide initiated with α,α‐azobisisobutyronitrile was carried out to produce amphiphilic microspheres containing benzyl chloromethyl groups. The structure of the amphiphilic microspheres was determined by IR and 1H‐NMR spectroscopy. The polymerization conditions, the temperature, amount of crosslinking agent, and initiator included, were optimized. The size distribution of the microspheres after swelling equilibrium ranged from 4 to 62 μm. The swelling behavior of the microspheres was also investigated. The increase in temperature and the decrease in salinity caused a gradual increase in the swelling ratio. The prepared microspheres were transported uniformly in porous media when the permeability was 0.436 μm2. The oil displacement experiments indicated that amphiphilic microspheres had the ability to enhance oil recovery under homogeneous and heterogeneous conditions but was more suitable for heterogeneous formation. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41578.

Pyrimidine-5-carbonitriles – part III: synthesis and antimicrobial activity of novel 6-(2-substituted propyl)-2,4-disubstituted pyrimidine-5-carbonitriles

Abstract The reaction of 6-(2-methylpropyl or 2-phenylpropyl)-2-thiouracil-5-carbonitriles (4a,b) with various arylmethyl halides, 2-bromoethyl methyl ether, benzyl chloromethyl ether, and 2-bromomethyl-5-nitrofuran in N,N-dimethylformamide or acetone yielded the corresponding substituted thio-3,4-dihydro-4-oxopyrimidine-5-carbonitrile analogues 5a–h, 6a,b, 7, and 8a,b, respectively. Treatment of 5c with phosphorus oxychloride and N,N-dimethylaniline yielded the 4-chloropyrimidine derivative 9, which was allowed to react with various arylthiols, arylamines, and 1-substituted piperazines to yield the respective 4-arylthio 10a–d, 4-arylamino 11a–d, and 4-piperazino 12a,b derivatives. The newly synthesized compounds were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compounds 5e, 5f, 5g,h, 7, 8a,b, and 12a display marked antibacterial activity, particularly against the Gram-positive bacteria. None of these compounds are active against C. albicans.

ChemInform Abstract: Reactions of Carbonyl Compounds with Benzyl Chloromethyl Ether of Diiodomethane in the Presence of Samarium(II) Iodide or Metallic Samarium. New Routes to 1,2-Diols, Iodohydrins and Cyclopropanols.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Angular Hydroxymethylation of Functionalized Decalin Systems.

Functionalized β-dicarbonyl bicyclic compounds were hydroxymethylated at the angular position as the (benzyloxy) methoxy derivatives with diisopropylethylamine (DIPEA) and benzyl chloromethyl ether in the presence of paraformaldehyde

Synthesis of Novel Uracil Non‐Nucleoside Derivatives as Potential Reverse Transcriptase Inhibitors of HIV‐1

Novel emivirine and TNK-651 analogues 5a-d were synthesized by reaction of chloromethyl ethyl ether and / or benzyl chloromethyl ether, respectively, with uracils having 5-ethyl and 6-(4-methylbenzyl) or 6-(3,4-dimethoxybenzyl) substituents. A series of new uracil non-nucleosides substituted at N-1 with cyclopropylmethyloxymethyl 9a-d, 2-phenylethyloxymethyl 9e-h, and 3-phenylprop-1-yloxymethyl 9i-l were prepared on treatment of the corresponding uracils with the appropriate acetals 8a-c. Some of the tested compounds showed good activity against HIV-1 wild type. Among them, 1-cyclopropylmethyloxymethyl-5-ethyl-6-(3,5-dimethylbenzyl)uracil 9c and 5-ethyl-6-(3,5-dimethylbenzyl)-1-(2-phenylethyloxymethyl)uracil 9g showed inhibitory potency equally to emivirine against HIV-1 wild type. Furthermore, compounds 9c and 9g showed marginal better activity against NNRTI resistant mutants than emivirine.

ChemInform Abstract: In situ Synthesis of Benzyl Chloromethyl Ether and Its Use for the Protection and Deprotection of Bifunctional Hydroxyl Compounds.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

In Situ Synthesis of Benzyl Chloromethyl Ether and its Use for the Protection and Deprotection of Bifunctional Hydroxyl Compounds

In situ synthesis of benzyl chloromethyl ether and its use to protect bifunctional hydroxyl compounds as benzyloxymethyl ethers is reported. This methodology was extended to alkylate the N-protected L-amino acids. Keywords: Benzyl chloromethyl ether, protection, deprotection

Synthesis of New Quinazoline-2,4(1H,3H)-dione non-nucleoside Analogues of the reverse transcriptase inhibitor TNK-651

The synthesis is described of a series of new non-nucleoside analogues of the reverse transcriptase inhibitor TNK-651 from quinazoline-2,4(1 H,3 H)-diones. Compounds 2a–c were silylated and treated with benzyl chloromethyl ether in the presence of CsI to give 1-benzyloxymethylquinazoline derivatives 3a–c. Treatment of the silylated quinazolinediones 2a–c with the appropriate acetals 5a–e in the presence of TMS triflate afforded the corresponding TNK-651 analogues 6–10.

Synthesis of Novel Uracil Non-Nucleosides Analogues of 3,4-Dihydro-2-Alkylthio-6-benzyl-4-oxopyrimidines and 6-benzyl-1-ethoxymethyl-5-isopropyluracil

A series of new uracil non-nucleosides analogues of S-DABO's was synthesised by reaction of 5-alkyl-6-( p-chlorobenzyl)-2-thiouracils with chloroethyl dialkylamine hydrochloride, N-(2-chloroethyl)-pyrrolidine hydrochloride, N-(2-chloroethyl)-piperidine hydrochloride or appropriate haloethers. Novel emivirine analogues were synthesised by silylation of 5-alkyl-6-( p-chlorobenzyl)uracils and treatment with bromomethyl methyl ether, chloromethyl ethyl ether or benzyl chloromethyl ether. Compounds 6-( p-chlorobenzyl)-5-ethyl-1-ethyloxymethyluracil (9e) and 1-benzyloxymethyl-6-(4-chlorobenzyl)-5-ethyluracil (9f) showed activity against wild-type HIV-1 strain III B in MT-4 cells.

Synthesis and Biological Evaluation of N-Formyl Hydroxylamine Derivatives as Potent Peptide Deformylase Inhibitors

Antibacterial resistance to hospital-acquired Grampositive bacterial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), and vancomycin-resistant enterococci (VRE), has been increasing at an alarming rate. Therefore there is an urgent need to identify novel antibacterial drugs with new modes of action. Peptide deformylase (PDF), which catalyzes the removal of the N-terminal formyl group from newly synthesized polypeptides and is essential in a variety of pathogenic bacteria but is not required for cytoplasmic protein synthesis in eukaryotes, is an attractive target for the discovery of novel antibiotics. Many PDF inhibitors have been reported in recent years, some of which showed excellent antibacterial activity in vitro and in animal models. Amongst these inhibitors, NVPPDF-713 (2, Vicuron and Novartis) and BB-83698 (3, Vernalis) are currently in phase I clinical trials for the treatment of respiratory tract infections (Fig. 1). Based on the mechanism of deformylation of peptides and the pharmacophore requirements for PDF inhibitor, a new series of arylamidopiperidine derivatives at the P3' position was designed and synthesized. We chose tert-leucine as the P2' residue because other PDF inhibitors containing this P2' residue have shown excellent antibacterial activity and bioavailability. We report here the synthesis and preliminary in vitro evaluation of a new series of PDF inhibitors having an arylamidopiperidine at P3' position. The general route for the synthesis of the arylamidopiperidine derivatives is outlined in Scheme 1. The 1-Boc-4aminopiperidine 6 was prepared in two steps from commercially available N-Boc-piperidin-4-one 5 by reductive amination with benzyl amine followed by hydrogenolysis of the benzyl group. Acylation of the 4-amino group was readily accomplished by treating 6 with p-substituted benzoyl chloride to yield intermediate 7. The piperidine hydrochloride 7 was subsequently coupled by standard peptide coupling conditions using N-Boc-L-tert-leucine to give amide 8. Removal of the N-Boc group with HCl (g)/EtOAc gave amine hydrochloride 9. The N-formyl hydroxylamine analogues were synthesized as shown in Scheme 2. The required chiral intermediate 11 containing the P1' residue was prepared by using Evan’s asymmetric alkylation methodology described previously literature. Reaction of (S)-4-benzyl-2-oxazolidinone with acid 10 in the presence of n-BuLi provided the corresponding oxazolidinone amide. Trichlorotitanium enolate of oxazolidinone amide in CH2Cl2 was obtained by treatment of the amide successively with 1.1 equiv each of TiCl4 and Et3N. Subsequent treatment of this enolate with 2.0 equiv of benzyl chloromethyl ether provided 11 selectively in 90% yield. Removal of the auxiliary group of 11 by hydrolysis under

2,3]‐Wittig Rearrangement by a Chlorine—Lithium Exchange.

AbstractFor Abstract see ChemInform Abstract in Full Text.

2,3]-Wittig rearrangement by a chlorine–lithium exchange

The reaction of different allylic chloromethyl ethers 1 with an excess of lithium powder (1:7 molar ratio) and a catalytic amount of DTBB (2.5 mol %) in THF at 0 °C for 1 h gives, after hydrolysis with water, the expected alcohols 2 resulting from a [2,3]-Wittig rearrangement, in an exclusive manner. The same process can also be applied to the corresponding [1,2]-Wittig rearrangement, as it is exemplified for benzyl chloromethyl ether.

The Nonchiral Bislactim Diethoxy Ether as a Highly Stereo‐Inducing Synthon for Sterically Hindered, γ‐Branched α‐Amino Acids: A Practical, Large‐Scale Route to an Intermediate of the Novel Renin Inhibitor Aliskiren

AbstractThe diastereoselective synthesis of the sterically hindered, γ‐branched α‐amino acid derivative (2S,4S)‐24a and its N‐[(tert‐butoxy)carbonyl](Boc)‐protected alcohol (2S,4S)‐19, both key intermediates of a novel class of nonpeptide renin inhibitors such as aliskiren (1), is described. Initially, the analogous methyl ester (2S,4S)‐17 was obtained by alkylation of the chiral Schöllkopf dihydropyrazine (R)‐12a with the dialkoxy‐substituted alkyl bromide (R)‐11a, which proceeded with explicitly high diastereofacial selectivity (ds ≥98%) to give (2S,5R,2′S)‐13a (Scheme 4), followed by mild acid hydrolysis and N‐Boc protection (Scheme 5). Conversely, the complete lack of stereocontrol and poor yields for the reaction of (R)‐11a with the enantiomeric (S)‐12b suggested, in addition to the anticipated shielding effect by the iPr group at C(2) of the auxiliary, steric repulsion between the MeOC(6) and the bulky residues of (R)‐11a in the proposed transition state, which would strongly disfavor both the Si and Re attack of the electrophile (see Fig.). Based on this rationale, alkylation of the readily accessible achiral diethoxy‐dihydropyrazine 21 with (R)‐11a was found to provide a 95 : 5 mixture of diastereoisomers (2S,2′S)‐22a and (2R,2′S)‐23a in high yield (Scheme 6), which afforded in two steps and after recrystallization enantiomerically pure (2S,4S)‐24a. Similarly, the stereochemical course for the alkylation reactions of the related alkyl bromides (S)‐28a and (R)‐28b with both (R)‐12a and (S)‐12b as well as with the achiral 21 was investigated (Schemes 7–9). The precursor bromides (R)‐11a, (S)‐11b, (R)‐28a, and (S)‐28b were efficiently synthesized via the diastereoselective alkylation of the Evans 3‐isovaleroyloxazolidin‐2‐ones (R)‐7a and (S)‐7b either with bromide 6 or with benzyl chloromethyl ether, and subsequent standard transformations (Schemes 3 and 7). A practical and economical protocol of the preparation of (2S,4S)‐24a on a multi‐100‐g scale is given. This is the first report of the application of an achiral dihydropyrazine, i.e., in form of 21, as a highly stereo‐inducing synthon providing rapid access to a N‐protected γ‐branched α‐amino acid with (2S) absolute configuration.

Synthesis of New Uracil Non‐nucleoside Derivatives as Potential Inhibitors of HIV‐1.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of new uracil non‐nucleoside derivatives as potential inhibitors of HIV‐1

Abstract6‐(2‐Phenylethyl) and 6‐cyclohexyl 5‐cyanouracils (1a,b) were synthesized and reacted with chloromethyl ethyl ether, benzyl chloromethyl ether, chloromethyl methyl sulfide and (2‐acetoxyethoxy)methyl bromide. New uracil analogues of (S)‐DHPA were synthesized by reaction of compounds (1a,b) with ((S)‐2,2‐dimethyl‐1,3‐dioxolane‐4‐yl) alkyl p‐toluenesulfonate.

ChemInform Abstract: A Novel Synthetic Route for the Preparation of Alkyl and Benzyl Chloromethyl Phosphates.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A novel synthetic route for the preparation of alkyl and benzyl chloromethyl phosphates

An efficient and simple synthesis is described for the production of various chloromethyl phosphates as useful reagents for the preparation of phosphonooxymethyl prodrugs.

Enantioselective synthesis of imperanene, a platelet aggregation inhibitor.

Both enantiomers of imperanene, a platelet aggregation inhibitor, have been synthesized in 82-90% ee. The key step of establishing the chiral center was achieved through stereoselective alkylation with benzyl chloromethyl ether using Enders' RAMP/SAMP chiral auxiliary method. The natural product was determined to be the (S)-enantiomer through comparison of optical rotation data. Reaction: see text.

Synthesis of 1-(aryloxyalkyl)- 5-(arylamino)uracils

In an attempt to obtain new non-nucleoside inhibitors of the reverse transcriptase HIV-1, we have carried out the synthesis of 1-(benzyloxymethyl)- and 1-[2-(4-R-phenoxy)ethyl]-5-(arylamino)uracils. Indirect alkylation of trimethylsilyl derivatives of 5-(arylamino)uracils with benzyl chloromethyl ether by the Gilbert-Jones method did not affect the exocyclic amino group and gave the corresponding 1-(benzyloxymethyl) derivatives in 58–74% yield. Alkylation of 5-(arylamino)uracils with 1-bromo-2-(4-R-phenoxy)ethane in anhydrous DMF in the presence of potassium carbonate gave a mixture of N1-mono- and N1, N1-disubstituted products with an overall yield of 46–55%.