Molecular conformations of methyl formate and methyl vinyl ether from ab initio molecular orbital calculations

Ab initio molecular orbital theory with minimal and extended basis sets and a flexible rotor geometric model has been used to investigate the rotational potential surfaces of methyl formate and methyl vinyl ether. For both molecules, the most stable structures (IA and IIA, respectively) are planar cis; additional potential minima are found which correspond to planar trans structures (IB and IIB). The latter lie respectively about 4—8 and 1—2 kcal mol^?1 above the corresponding cis rotational isomers. Methyl rotational barriers have been determined for cis and trans structures of each molecule. For trans methyl formate, there is a slight but unexpected preference for an eclipsed arrangement of the methyl group.     

Synthesis of 4,5-dihydro-4-methyl-1-phenyl-1,4,5-benzotriazocine-2,3,6(1H) triones

The title compounds, 7a and its 9-chloro analog 7b , were prepared in three steps from methyl N-phenylanthranilates. Thus, methyl N-phenylanthranilate ( 3a ) was treated with oxalyl chloride to yield 2-[(2-chloro-1, 2-dioxoethyl) phenylamino]benzoic acid methyl ester ( 4a ). Treatment of 4a with methylhydrazine gave 2-([2-(1-methylhydrazino)-1,2-dioxoethyl]phenylamino) benzoic acid methyl ester ( 6a ), which was cyclized with sodium hydride in dimethylformamide to produce 7a . Alkylation of 7a and 7b with iodomethane afforded the respective 5-methyl derivatives 8a and 8b . A survey of the known literature benzotriazocines is presented.     

The Wittig–Horner reaction for the synthesis of neratinib

The Wittig–Horner reaction is a classic method to get alkenes by reaction phosphonates with carbonyl compounds. In this study, it was used for the synthesis of the anticancer drug neratinib. In this method, ethyl diethoxyphosphinylacetate and dimethylaminoacetaldehyde diethylacetal, replacing (E)-4-(dimethylamino)but-2-enoyl acid hydrochloride and oxalyl chloride, were used to synthesize the 6-position side chain of neratinib.     

Microwave spectrum of propionyl chloride

The microwave spectrum of propionyl chloride has been investigated in the region 18.0–40.0 GHz, and transitions due to a cis conformer have been assigned. This form has a heavy atom planar configuration and the methyl group and the carbonyl oxygen atom are cis to each other. Using the substitution structures of propionic acid and acetyl chloride as molecular models for the propionyl chloride molecule, good agreement is found between observed and calculateò effective rotational constants. For the ³⁵Cl species satellite spectra assigned to the first four excited states of the C-C torsional mode have been observed together with the first excited state of the methyl torsional mode. The ground state spectrum has also been assigned for the ³⁷Cl species. Relative intensity measurements yielded the lowest C-C torsional vibration frequency of 86 ± 10 cm^?1. The CH₃ internal rotation frequency was found to be 197 cm^?1. Nuclear quadrupole coupling constants were determined for the ground state of the ³⁵Cl and ³⁷Cl species. From observed A-E splittings of ^bQ-branch transitions of the first excited state of the methyl torsional mode a barrier to internal rotation was estimated to be V₃ = 2480 ± 40 cal mol^?1 (867 ± 14 cm^?1).     

Chiral recognition of amino esters by a ruthenium porphyrin complex: kinetics of the exchange process determined by 1H NMR

The synthesis of a (carbonyl) (valine methyl ester) ruthenium(II) picket-fence complex bearing optically active α-methoxy-α(trifluoromethyl)phenylacetyl residues on both sides of the porphyrin plane (α,β,α,β-isomer) is described. For various amino esters, chiral recognition was observed for the complexation of the ligand with up to 52% enantiomeric excess for tert-leucine methyl ester. The dissociation rate constants of the two enantiomers of valine methyl ester were determined by ¹H NMR using magnetization transfer experiments, showing that the origin of the enantioselectivity in favour of the (l)-valine (ca. 2.6:1) resides in the difference between the kinetics of the axial ligand dissociation of the two enantiomers.     

1,6- and 1,7-naphthyridines. II. Synthesis from acyclic precursors

A number of 8-hydroxy-6-methyl-1,6-naphthyridin-5(6H)-one-7-carboxylic acid alkyl esters 3 and the isomeric 5-hydroxy-7-methyl-1,7-naphthyridin-8(7H)-one-6-carboxylic acid alkyl esters 4 were synthesized from acyclic precursors obtained starting from quinolinic anhydride 5. Thus, methanolysis of 5 afforded the hemiester 6 which treated with oxalyl chloride and sarcosine ethyl ester gave 3-(N-ethoxycarbonylmethyl-N-methylcarbamoyl)pyridine-2-carboxylic acid methyl ester 8. Compound 8 was cyclized to naphthyridines 3a-e with sodium alkoxides. The isomeric naphthyridines 4a-c were obtained by cyclization of the open intermediary 2-(N-ethoxycarbonylmethyl-N-methylcarbamoyl)pyridine-3-carboxylic acid methyl ester 9 obtained by a route that involves treatment of 5 with sarcosine ethyl ester and esterification with diazomethane. Spectroscopic properties (¹H nmr, uv, ir) of compounds 3 and 4 are discussed and confirmed the proposed structures.     

Preparation of the Key Dolutegravir Intermediate via MgBr2-Promoted Cyclization

A novel approach for synthesizing the key dolutegravir intermediate is described via MgBr₂-promoted intramolecular cyclization. Condensation of commercially available methyl oxalyl chloride and ethyl 3-(N,N-dimethylamino)acrylate afforded the vinylogous amide in an excellent yield. Subsequent substitution by aminoacetaldehyde dimethyl acetal and methyl bromoacetate gave rise to the expected precursor for cyclization, which was promoted by MgBr₂ to highly selectively convert into pyridinone diester. The key dolutegravir intermediate was finally prepared by the selective hydrolysis of the corresponding diester via LiOH.     

Reactions of 2-isocyanatobenzoyl chloride and 2-carbomethoxyphenyl isocyanate with 5-aminotetrazole

Treatment of 2-isocyanatobenzoyl chloride ( 4 ) with 5-aminotetrazole (5-AT) gave 3-(5-tetrazolyl)quinazoline-2,4(1H,3H)-dione ( 1 ) directly. Treatment of 2-carbomethoxyphenyl isocyanate ( 5 ) with 5-AT gave 2-[((5-amino-1H-tetrazol-1-yl)carbonyl)amino]benzoic acid methyl ester ( 6 ) as a kinetic product, which was thermally isomerized to 2-[((1H-tetrazol-5-ylamino)carbonyl)amino]benzoic acid methyl ester ( 7 ), the thermodynamically more stable urea. Cyclization of 7 with polyphosphoric acid gave 2-(1H-tetrazol-5-ylamino)-4H-3,1-benzoxazin-4-one ( 2 ). Urea 6 was quite labile in solution, as shown by nmr, and readily reacted with methanol to give 2-[(methoxycarbonyl)amino]benzoic acid methyl ester ( 10 ).     

Coordination isomerism of the complex of o-methoxybenzoyl chloride with tetrachlorostannane. The results of ab initio calculations

Quantum-chemical calculations of three isomers of the o-methoxybenzoyl chloride complex with tetrachlorostannane and of their components were performed applying the RHF/3-21G* and MP2/3-21G* methods. It was found that a complex with trigonal-bipyramidal structure is formed, its formation occurred through the interaction of ester (not carbonyl) oxygen atom with tin atom. This complex eventually is transformed into the energetically more favorable cis-octahedral complex of the same composition. The tin atom in the latter complex interacts with two oxygen atoms. The reasons for the formation of energetically unfavorable complex of trigonal-bipyramidal structure is the almost equal probability of the existence of various possible forms of o-methoxybenzoyl chloride and therefore higher probability of the Sn atom to interact with the ester oxygen atom possessing a much more negative charge than the carbonyl oxygen.     

A modified method for determination of boron with curcumin and a simplified water elimination procedure

The formation of boric acid ester with curcumin is usually performed in highly acidic solution in the absence of water. Small water contents are permissible, but the efficiency is lowered. The water content of a sample can be eliminated by a reaction with propionic anhydride catalyzed by oxalyl chloride, thus avoiding methyl borate distillation or evaporation processes. An advantage is that the reaction between boron and curcumin takes place in a completely homogeneous liquid medium. The excess of protonated curcumin is best destroyed with an ammonium acetate buffer. For trace amounts of boron, extraction of the coloured complex with a mixture of methyl isobutyl ketone, chloroform and phenol is recommended. Standard procedures for aqueous solutions with boron contents between 0.0033–40.0 μg B/l are described.     

Efficient preparation of dichloromethyl alkyl ethers and their application in the formylation of aromatic compounds: Scope and limitations

Practical preparations of dichloromethyl alkyl ethers are described, based on the reaction of alkyl formates with oxalyl chloride in the presence of N-methylformanilide. The method involves a simple procedure that does not require the use of harmful reagents. Dichloromethyl propyl and dichloromethyl butyl ethers represent secure synthetic equivalents to dichloromethyl methyl ether. Formylations of both electron-deficient and electron-rich aromatics with these dichloromethyl alkyl ethers in the presence of AlCl₃, FeCl₃, or TiCl₄ have been systematically investigated. A plausible mechanism of formylation is discussed.     

A spectroscopic study of model urethanes

The synthesis, far infrared spectra, temperature-dependent mid-infrared spectra in the carbonyl and NH stretching regions and the Fourier transform Raman spectra are reported for polycrystalline samples of three small diurethanes, 1,3-phenyl di(carbamic acid methyl ester),2,6-toluene di(carbamic acid methyl ester) and 2,4-toluene di(carbamic acid methyl ester). An ab initio geometry optimization is reported for methyl N-phenyl carbamate using STO-3G and 3-21G basis sets, and for the three small diurethanes by molecular mechanics methods using the Dreiding I force field. The results suggest that, in isotropic surroundings, only a very small number of the 256 possible conformers of the urethane groups in the three small diurethanes contribute appreciably to the structure.     

Potential for rotation about C(sp2)-O and C(sp2)-S bonds: electron diffraction results for CH2CH-OCH3 and CH2

Electron diffraction of gaseous methyl vinyl ether and methyl vinyl sulphide show that both compounds exist as a mixture of two conformers, one of these is the syn form with a planar heavy atom skeleton. For methyl vinyl ether the second conformer may also have a planar skeleton (anti form), but a gauche form with a torsional angle close to 180° cannot be ruled out. For the sulphide a gauche form is found. Structural parameters are given in Table 2. Ab initio calculations gave energy minima for syn and anti forms for CH₂CH-OH and for syn and gauche forms for CH₂CH-SH.     

dl-六甲基化丹酚酸A甲酯的合成

以2,3二-甲氧基苯甲醛为原料,经还原、溴化、Wittig反应、在正丁基锂作用下醛基化、Knoevenagel反应生成四甲基化丹酚酸F(9),9再与草酰氯反应成酰氯后与甲基化丹参素甲酯反应得到dl-六甲基化丹酚酸A甲酯,其结构经1HNMR和MS表征,总收率44.7%。     

Electric dipole moment studies of carboxylic ester conformations: alkyl acetates,benzoates, 2,4,6-trimethyl-benzoates and 2,3,5,6-tetramethylbenzoates

Electric dipole moments μ in benzene at 30 °C have been determined (Table 3) on methyl, ethyl, isopropyl and t-butyl esters of the title compounds to determine steric effects on conformation in solution. Experimental moments were compared with those calculated for various possible conformations by a 3-dimensional vectorial addition method using bond moments and bond angles. The experimental moments for the alkyl acetates were best interpreted in terms of an out-of-plane deviation of the alkyl group from an s-trans conformation caused by steric interference between the alkyl group and the carbonyl oxygen and increasing in the series from methyl to t-butyl. The dihedral angles 0 (deviations) were calculated using a vector addition method. An increase in the moments of the benzoate series over the acetates was interpreted in terms of conjugative interaction between phenyl and carbonyl groups. Angles of twist φ for the benzoates and trimethylbenzoates were calculated using the Braude-Sondheimer equation. A decrease in the moments of the methyl, ethyl, and isopropyl trimethyl-benzoates as compared with the benzoates was interpreted in terms of steric interference between ortho methyls and both oxygens. The decrease in the angles of twist from methyl to t-butyl for the trimethylbenzoates was tentatively explained by greater steric interaction of the alkyl group with both carbonyl oxygen and ortho methyls, which forces adoption of a more coplanar arrangement between the ring and the carbonyl group than for the other alkyl derivatives, this interaction increasing with the size of the alkyl group. Dipole moments for 2,3,5,6-tetramethylbenzoates were nearly the same as for corresponding trimethyl-benzoates, thus showing no conclusive evidence for operation of a “buttressing” effect.     

Diethyl piperazine‐1,4‐diyldioxalate

The ethyl oxamate group, N–C(O)–C(O)–OEt, in the title compound, alternatively called diethyl N,N′:N,N′‐bis(ethylene)dioxamate, C₁₂H₁₈N₂O₆, can be considered as being composed of two singly bonded amide and ester functionalities. The ethyl oxamate group is not planar. The two carbonyl groups are almost perpendicular, with an oxalyl O=C—C=O torsion angle of −111.34 (17)°. The mol­ecule is located on an inversion centre. Infinite supramolecular tapes, propagating along the b axis, are formed through soft C—H⋯O interactions which form a centrosymmetric R(12) motif.     

Reactions of ethyl 6,6-dialkyl-8,9-dioxo-5,6,8,9-tetrahydrobenzo[<Emphasis Type="Italic">f</Emphasis>]pyrrolo[2,1-<Emphasis Type="Italic">a</Emphasis>]isoquinoline-10-carboxylates with <Emphasis Type="Italic">N</Emphasis>-nucleophiles

Reaction of enaminoesters, derivatives of 2,2-dialkyl-1,2,3,4-tetrahydrobenzo[f]isoquinoline, with oxalyl chloride leads to the formation of ethyl 6,6-dialkyl-8,9-dioxo-5,6,8,9-tetrahydrobenzo[f]pyrrolo[2,1-a]-isoquinoline-10-carboxylates. At reaction of the latter with ammonia and cyclic amines opening of pyrroledione cycle occurs and the formation of enaminoketoamides, and the reaction with o-phenylenediamine furnishes a fragment of benzimidazole. Hydroxylamine behaves as binucleophile and attacks not only lactam, but also the ester group, affording heterocyclic system of isoxazine-3,4,6-trione.     

Novel synthesis of the pyrrolo[2,1-c][1,4]benzodiazocine ring system via a Dieckmann condensation

A novel four-step synthesis to the pyrrolo[2,1-c][1,4]benzodiazocine ring system is described. 1H-Pyrrole-2-carbaldehyde was alkylated with ethyl or methyl bromoacetate and the resulting ethyl or methyl (2-formyl-1H-pyrrol-1-yl)acetates oxidised with potassium permanganate to the corresponding 1-[(2-ethoxy or methoxy)-2-oxoethyl]-1H-pyrrole-2-carboxylic acids. The latter was converted into their acid chlorides by reaction with thionyl chloride and without isolation transformed into the respective methyl 2-({[1-(2-ethoxy or methoxy-2-oxoethyl)-1H-pyrrol-2-yl]carbonyl}amino)benzoates by reaction with methyl anthranilate. Dieckmann condensation of methyl 2-({[1-(2-methoxy-2-oxoethyl)-1H-pyrrol-2-yl]carbonyl}amino)benzoate provided the pyrrolo[2,1-c][1,4]benzodiazocine.     

Isosteviol derivatives having azine and hydrazide fragments

Diterpenoid isosteviol (ent-16-oxobeyeran-19-oic acid) and its methyl ester and chloride reacted with hydrazine hydrate to give derivatives having azine and hydrazide fragments.     

The Vilsmeier reagent: a useful and versatile reagent for the synthesis of 2-azetidinones

(Chloromethylene)dimethylammonium chloride (Vilsmeier reagent), prepared easily from N,N-dimethylformamide and oxalyl chloride or thionyl chloride, works as a versatile acid activator reagent for the direct [2+2] ketene-imine cycloaddition of substituted acetic acid and imines in one-pot synthesis under mild conditions. Monocyclic, spirocyclic and 3-electron-withdrawing group β-lactams were synthesized by this method and optimization of conditions were performed.