Showing papers on "Diazomethane published in 2010"

Reactivity of germanium(II) hydride with nitrous oxide, trimethylsilyl azide, ketones, and alkynes and the reaction of a methyl analogue with trimethylsilyl diazomethane.

Abstract: The reactions of stable β-diketiminate germanium(II) hydride LGeH (1) [L = HC(CMeNAr)2, Ar = 2,6-iPr2C6H3] with nitrous oxide, trimethylsilyl azide, ketones, and alkynes are described. 1 reacts with nitrous oxide to yield the germanium(II) hydroxide LGeOH (2), and with trimethylsilyl azide affords in toluene at room temperature the germanium(II) azide LGeN3 (3), and also the germanium(IV) diamide L′Ge(NHSiMe3)2 (L′ = CH{(CCH2)(CMe)(2,6-iPr2C6H3N)2}) (4). Ketones (PhCOCF3, 2-C4H3SCOCF3) and 1 generated the germanium(II) alkoxides (5–6) in high yield. The activated terminal alkyne (HCCCO2Me) and disubstituted alkyne (EtO2CCCCO2Et) react with 1 to form the germanium(II) substituted alkenes (vinyl germylene) (7–8). Further reaction of the methylgermanium(II) compound LGeMe (9) with trimethylsilyl diazomethane resulted in the formation of germanium(IV) amide L′Ge(Me)NHNCHSiMe3 (10). Compounds 2–8, and 10 were characterized by microanalysis and multi-nuclear NMR spectroscopy. Furthermore compounds 3–6, and 8 are confirmed by X-ray structural analysis.

Improved Arndt-Eistert synthesis of alpha-diazoketones requiring minimal diazomethane in the presence of calcium oxide as acid scavenger.

Abstract: A practical methodology to obtain alpha-diazoketones through an improved Arndt-Eistert synthesis is described The method allows the efficient transformation of acid halides using a stoichiometric amount of diazomethane in the presence of calcium oxide, without concomitant ketene or haloketone formation The obtained alpha'-brominated-alpha-diazoketones were employed as suitable substrates for the synthesis of interesting alpha-arylamino-alpha'-halomethylketones

Diazo compounds in the chemistry of fullerenes

Abstract: Experimental and theoretical data on the reactions of different diazo compounds (diazomethane, its derivatives, cyclic diazo compounds and diazocarbonyl compounds) with fullerenes are summarized. The structures and stereochemistry of cycloadducts formed in these reactions are considered.

A preparation of N-Fmoc-N-methyl-α-amino acids and N-nosyl-N-methyl-α-amino acids

Abstract: A convenient route for the synthesis of lipophilic N-Fmoc-N-methyl-α-amino acids and N-nosyl-N-methyl-α-amino acids, interesting building blocks to be used for the preparation of N-methylated peptides, is presented. Both nosyl- and Fmoc-protected monomers are accessible, so these compounds can be used in solution as well as in solid phase peptide synthesis. The methodology is based on the use of benzhydryl group to protect temporarily the carboxyl function of N-nosyl-α-amino acids and on the subsequent methylation of the N-nosyl-α-amino acid benzhydryl esters with diazomethane. The benzhydryl esters offer several beneficial features such as simple preparation, stability to methylation and selective deprotection under mild conditions. The overall procedure is highly efficient in that the adopted conditions keep the chiral integrity of amino acid precursors and the process does not require chromatographic purification of the methylated products.

A method for concurrent diazomethane synthesis and substrate methylation in a 96-sample format

Abstract: In the emerging field of metabolomics, there is an increasing need for improving sample derivatization reactions for gas chromatographic-mass spectral analysis of metabolites with large numbers of samples. This protocol details the safe direct derivatization of organic acids using diazomethane in a 96-sample format. Diazomethane is a highly reactive gas that readily forms methyl esters with carboxylic functionalities, with minimal side products or nonvolatile reaction residues. However, diazomethane's reactivity and explosive potential make it hazardous to store and work with. In this procedure, diazomethane is generated in situ and used concurrently to methylate up to 96 samples simultaneously, thus reducing concerns about reagent stability and obviating the need for storage of solutions of the highly reactive gas. Once the diazomethane generator has been assembled, processing 96 samples takes 2-3 h using this procedure.

Mimosine (leucaenine) 5th communication )

Abstract: The identity of mimosine from Mimosa pudica and of l-leucaenine from Leucaena glauca Bentham is proved by means of a mixed melting point and Debije-Scherrer diagram. The action of diazomethane on the dihydrochloride of mimosine methyl ester leads to a total degradation of the molecule, by which the pyridine ring is broken. Amongst other things there is produced a compound C4H8O3N2 and 3: 4-dimethoxy-pyridine. The same compounds are produced by the action of diazomethane on 3-methoxy-4-pyridone. Some of the properties of mimosine are in agreement with the assumption of a polar structure, which is comparable with a β-betaine.

Synthesis of new spiro compounds containing a carbamate group

Abstract: 1,3-Dipolar cycloaddition to methyl 4-[2-(2-oxo-2,3-dihydro-1H-indol-3-ylidene)-1-oxoethyl]-phenylcarbamate of diazomethane in chloroform-diethyl ether and of 3,4-dimethoxybenzonitrile oxide generated from the corresponding aldehyde oxime by the action of N-chlorobenzenesulfonamide sodium salt (Chloramine B) in boiling ethanol gave, respectively, methyl 4-(2-oxo-1′,5′-dihydro-1H-spiro[indole-3,4′-pyrazol]-3′-ylcarbonyl)phenylcarbamate and methyl 4-[3′-(3,4-dimethoxyphenyl)-2-oxo-1H,4′H-spiro[indole-3,5′-isoxazol]-4′-ylcarbonyl]phenylcarbamate The condensation of methyl 4-[2-(2-oxo-2,3-dihydro-1H-indol-3-ylidene)-1-oxoethyl]phenylcarbamate with hydrazine hydrate in ethanol afforded methyl 4-(2-oxo-1,2,2′,4′-tetrahydrospiro[indole-3,3′-pyrazol]-5′-yl)phenylcarbamate

Nucleophilic aromatic addition: I. The reaction of diazomethane with 1,3,5-trinitrobenzene

Abstract: The structure of the reaction product from 1,3,5-trinitrobenzene and an excess (i.e. at least four moles) of diazomethane, as found many years ago by Heinke, is shown to be a seven-membered ring-compound condensed with two cyclopropane rings and with one pyrazoline ring (VII). If 1,3,5-trinitrobenzene is treated with diazomethane in a molar ratio of 1:3, no pyrazoline derivative is formed, but a hitherto unknown “tris-methylene” derivative (VI), containing a seven-membered ring system condensed with two cyclopropane rings. This remarkably stable compound is an intermediate in the reaction with excess of diazomethane. When the molar ratio of the reactants is reduced to 1 : 2 or 1 : 1, the “trismethylene” derivative (VI) results, together with unchanged 1,3,5-trinitrobenzene.

An efficient route for the synthesis of a Tin(II) substituted carbodiimide from a diazo compound.

Abstract: The reaction of β-diketiminate substituted tin(II) chloride, LSnCl (1; L = HC{(CMe)(2,6-iPr2C6H3N)}2), with the lithium salt of trimethylsilyl diazomethane (LiC(N2)SiMe3) is described. In the course of the reaction, the exclusive formation of tin(II) substituted carbodiimide LSnNCNSiMe3 (2) is observed in good yield. This reaction occurs at room temperature without any side products. Furthermore, we reacted diiron nonacarbonyl, Fe2(CO)9, with compound 2 to confirm the carbodiimide skeleton (N═C═N) without rearrangement. The latter reaction leads to the tin(II) coordinate iron carbonyl complex LSnNCNSiMe3Fe(CO)4 (3). Compounds 2 and 3 were investigated by microanalysis and multinuclear NMR spectroscopy and were further characterized by X-ray structural analysis.

An efficient preparation of N-methyl-alpha-amino acids from N-nosyl-alpha-amino acid phenacyl esters.

Abstract: In this paper we describe a simple and efficient solution-phase synthesis of N-methyl-N-nosyl-α-amino acids and N-Fmoc-N-methyl-α-amino acids. This represents a very important application in peptide synthesis to obtain N-methylated peptides in both solution and solid phase. The developed methodology involves the use of N-nosyl-α-amino acids with the carboxyl function protected as a phenacyl ester and the methylating reagent diazomethane. An important aspect of this synthetic strategy is the possibility to selectively deprotect the carboxyl function or alternatively both amino and carboxyl moieties by using the same reagent with a different molar excess and under mild conditions. Furthermore, the adopted procedure keeps unchanged the acid-sensitive side chain protecting groups used in Fmoc-based synthetic strategies.

Preparation and diastereoisomerism of four substituted epoxycyclopentanones

Abstract: Epoxidation of 4-acetoxy-2-(6′-methoxycarbonylhexyl)-2-cyclopenten-1-one in alkaline medium yielded the two possible diastereoisomers of 2,3-epoxy-4-hydroxy-2-(6′-methoxycarbonylhexyl)-1-cyclopentanone. The structure and configuration of these compounds have been elucidated by first order analysis of the normal and spindecoupled proton magnetic resonance spectra. Both stereoisomeric epoxides can also be obtained via an alternative synthetic route by epoxidation of 2-(6′-carboxyhexyl)-4-hydroxy-2-cyclopenten-1-one. The separate cis and trans isomers of 2-(6′-carboxyhexyl)-2,3-epoxy-4-hydroxy-1-cyclopentanone are correlated with the stereoisomers of 2,3-epoxy-4-hydroxy-2-(6′-methoxycarbonylbexyl)-1-cyclopentanone by interconversion with diazomethane as well as by comparison of the proton spectra.

Cycloaddition of isothiocyanates with diazomethane and hydrazoic acid

Abstract: Methyl, phenyl and 1-alkenyl isothiocyanates 1 can react with diazomethane to give the corresponding 5-amino-1,2,3-thiadiazoles 4. In the presence of an excess of diazomethane these thiadiazoles rearrange to 1-substituted-5-(methylthio)-1H-1,2,3-triazoles 3. Reaction of 1-alkenyl isothiocyanate 1a with hydrazoic acid yields the corresponding 5-(1-alkenylamino)-1,2,3,4-thia-triazole 11, which does not rearrange when treated with diazomethane.

DFT investigation on mechanism of dirhodium tetracarboxylate-catalyzed O-H insertion of diazo compounds with H2O

Abstract: The mechanism of the dirhodium tetracarboxylate-catalyzed O-H insertion reaction of diazomethane and methyl diazoacetate with H2O has been studied in detail using DFT calculations. The rhodium catalyst and a diazo compound couple to form a rhodiumcarbene complex. Of two reaction pathways of the Rh(II)-carbene complex with H2O, the stepwise pathway is more preferable than the concerted one. Formation of a Rh(II) complex-associated oxonium ylide is an exothermal process, and direct decomposition of the ylide gives a very high barrier. The high barriers for the 1,2-H shift of Rh(II) complex-associated oxonium ylides make the ylides become stable intermediates in both reactions, especially for the reactions in solution. Difficulty in formation of a free oxonium ylide supports experimental results, indicating that the Rh(II) complex-catalyzed nucleophilic addition of a diazo compound proceeds via a Rh(II) complex-associated oxonium ylide rather than via a free oxonium ylide.

Comparison of two derivatisation methods for conjugated linoleic acid isomer analysis by Ag+‐HPLC/DAD in beef fat

Abstract: Two different procedures for the methylation of conjugated linoleic acid isomers (CLA) were compared by silver ion (Ag+)-HPLC. The base-catalysed method followed by an acid-catalysed method (NaOCH3/BF3), and base hydrolysis followed by methylation with diazomethane in diethyl ether (diazomethane) were used to prepare fatty acid methyl esters from lipids present in subcutaneous adipose tissue from beef steers. The repeatability θ of the two derivatisation methods was high (>0.9) for the major CLA isomers cis-9,trans-11 and trans-11,cis-13. A significant difference between the methods was found for the four isomers trans-11,trans-13, trans-10,trans-12, trans-9,trans-11, and trans-8,trans-10 and for the sum of total trans/trans isomers for both absolute (mg/100 g) and relative (%), which were higher with the NaOCH3/BF3 method. For the main isomer cis-9,trans-11 and the sum of total CLA isomers, a higher concentration was identified with the diazomethane method (781.2 mg/100 g vs. 749.3 mg/100 g and 991.59 vs. 962.99, respectively).

The reaction of diazomethane with benzoquinones

Abstract: The reaction of diazomethane with p-benzoquinone and several of its derivatives in the presence of an oxidizing agent leads to the formation of derivatives of isoindazole-4,7-quinone.

The low temperature reaction of diazomethane with 1,3,5-trinitrobenzene: Nucleophilic aromatic addition VIII

Abstract: There is a strong temperature effect on the reaction of 1,3,5-trinitrobenzene with diazomethane. At 0° three methylene groups are introduced and the product is the trinitro derivative I (found earlier). Below −80°, again three methylene groups are introduced, but the main product is a dinitro compound II, isomeric with I but with strikingly different properties. The methylene groups in II are incorporated in a seven-membered ring, a cyclopropane ring and an isoxazoline ring, the latter arising by an unusual participation of one of the nitro groups. The structural proof of II rests on spectroscopic evidence and specific chemical reactions.

Synthesis and reactivity of N-(4-pyridonyl)oxyacetic acid

Abstract: N-(4-Pyridonyl)oxyacetic acid was prepared in a yield of almost 60% by reacting 4-hydroxypyridine-N-oxide with chloroacetic acid in alkaline medium. The structure of N-(4-pyridonyl)oxyacetic acid follows from its decomposition when treated with sodium hydroxide solution and from its catalytical reduction, both reactions yielding 4-hydroxypyridine. A remarkable decomposition reaction of the acid occurs when it is treated with diazomethane. 4-Methoxypyridine is formed while carbon dioxide and formaldehyde are split off. The anomalous course of a condensation of the 3,5-diiodo-derivative of 4-hydroxypyridine-N-oxide with chloroacetic acid is explained.

Diazomethane on-line deriving method

Abstract: The invention relates to a diazomethane on-line deriving method, which comprises the following steps of: (1) a step of generating diazomethane; and (2) a step of deriving the diazomethane. The method can be realized under the action of N2. The method also comprises a tail gas absorption step after the step of deriving the diazomethane, wherein absorbent used in the tail gas absorption step for absorbing excessive diazomethane can be aether. The method also comprises a N2 flow rate control step before the step of generating the diazomethane and also comprises a diazomethane gas distribution step between (1) the step of generating the diazomethane and (2) the step of deriving the diazomethane. The method can be carried out in sealed environment. The diazomethane on-line deriving method can also comprise a step of exhausting the exhaust gas generated in the reaction from the sealed environment. The method organically integrates the preparation and the derivation of the diazomethane and has the characteristics of safety and high efficiency.

Site-Selective Methylation of Nβ-Nosyl Hydrazides of N-Nosyl Protected α-Amino Acids

Abstract: The methylation reaction of Nβ-nosyl hydrazides of N-nosyl protected α-amino acids by using diazomethane shows a controlled regiochemical trend and makes it possible to obtain the corresponding pro...

Compounds related to provitamin D3 (III)): Homocholesterol and the corresponding provitamin (3‐homoprovitamin D3)

Abstract: 3-Homocholesterol (III), obtained by action of LiAlH4 on cholesteryl-3-carboxylic methyl ester (II), which has been prepared from cholesteryl chloride by Grignard reaction, has the same steric configuration (β) at carbon atom 3 as cholesterol. Bromination of its acetate (IV) by means of bromosuccinimide, followed by elimination of HBr, leads to the acetate of 3-homoprovitamin D3 (Vα). This 3-homoprovitamin D3 (IX) can be synthesized with a far better yield by introducing first the double bond 7 and then the hydroxymethyl group 3. The magnesium derivative of 7-dehydrocholesteryl chloride is transformed by CO2 into the carboxylic acid (VII), which is readily methylated with diazomethane. Finally the 7-dehydrocholesteryl-3-carboxylic methyl ester (VIII) is reduced with LiAlH4 to 3-homoprovitamin D3 (IX). It is pointed out that the ultraviolet absorption characteristic for the conjugated system of double bonds 5-7 is subjected to an influence of molecular size.

Asymmetric Synthesis of Fluorine‐Containing Amines, Amino Alcohols, α‐ and β‐Amino Acids Mediated by Chiral Sulfinyl Group

Abstract: This review article provides a critical overview of several different synthetic approaches developed for asymmetric preparation of fluorine-containing amines, amino alcohols, α- and β-amino acids. The common feature of these methods is the application of sulfinyl group as a chiral auxiliary to control the stereochemical outcome of the reactions under study. In particular, the following general methods are critically discussed: diastereoselective methylene transfer from diazomethane to the carbonyl of β-keto-γ-fluoroalkyl sulfoxides as a general approach for preparation of various α-fluoroalkyl α-sulfinylalkyl oxiranes. The resulting compounds were used as true chiral synthons for their further elaboration via oxidative or reductive desulfurization, to numerous fluorine-containing and biologically relevant amino- and hydroxy-containing derivatives. Another general approaches discussed here are asymmetric additions to C N double bond. One of them is addition of chiral sulfoxide stabilized carbon nucleophiles to fluorine-containing imines, leading to convenient preparation of alpha-fluoroalkyl derivatives of alpha amino acids and amines. Another approach is asymmetric Reformatsky reaction between N -sulfinyl imines and ethyl bromodifluoroacetate allowing operationally convenient preparation of α,α-difluoro-β-amino acids in enantiomerically pure form. Finally, structurally similar but mechanistically different addition reactions of diethyl difluoromethylphosphonate to N -sulfinyl imines, as a general approach to asymmetric synthesis of α,α-difluoro-β-aminophosphonates and phosphonic acids, are discussed. Effect of fluorine on the mechanism and stereochemical outcome of these reactions is discussed in detail and compared, where it is possible, with that of the analogous reactions of fluorine-free substrates.

An efficient synthesis of methyl esters of heterocyclic α,β-didehydro-α-amino acid derivatives

Abstract: N-Benzoyl-protected α,β-didehydro-α-amino acid (DDAA) derivatives containing a pyrazole or an isoxazole ring at the β-position were transformed with diazomethane into the corresponding methyl esters. Applying this method, the double C=C bond of the DDAA derivatives was not affected, thus selectively giving the corresponding esters in good-to-excellent yields.

Aconic acid and related compounds: II. The reaction of aconic acid with diazomethane

Abstract: From aconic acid with an excess of diazomethane a nitrogen-containing compound is formed. The structure was established to be methyl 3,4-(4′,5′-Δ1-pyrazolino) aconate. Heating of this compound resulted in the splitting off of a molecule of nitrogen and the formation of a methyl-substituted aconic acid ester hitherto unknown in the literature.

Δ1‐pyrazolines: (Pyrazol and pyrazoline derivatives II

Abstract: Δ1-pyrazolines, in which the double bond is situated between the two nitrogen atoms can be prepared by the addition of diphenyldiazomethane to the diphenyl ester of citraconic acid and to the trimethyl ester of aconitic acid. These compounds split off nitrogen at higher temperatures forming cyclopropane derivatives. Diphenyl diazomethane combines directly with citraconic acid anhydride, splitting off nitrogen.