Elimination Of Dimethylamine Research Articles

Divergent Synthesis of Naphthalenone Spiroindanediones or 4‐Acyl‐1‐naphthols from Aryl Enaminones Featuring Reuse of Dimethylamine

AbstractPresented herein is a switchable synthesis of naphthalenone spiroindanediones or 4‐acyl‐1‐naphthols via condition‐controlled divergent cascade reactions of aryl enaminones with diazoindanediones. When the reaction was carried out in the presence of an oxidative additive, naphthalenone spiroindanedione was formed through C(sp2)−H alkylation followed by simultaneous spiroannulation and elimination of dimethylamine. When the reaction was carried out in the presence of an acid additive, on the other hand, 4‐acyl‐1‐naphthol was formed through ring opening of the spiroindanedione moiety attacked by the in situ released dimethylamine. In addition, the reactions are suitable for gram‐scale applications and compatible with a variety of substrates. Moreover, the naphthol products allow structural elaborations and hybridization with a drug, thus further enhancing the value of this developed method.

Surface reaction mechanism of atomic layer deposition of titanium nitride using Tetrakis(dimethylamino)titanium and ammonia

Atomic layer deposition (ALD) is an excellent technology used for the preparation of various nanomaterials in microelectronics, energy, catalysis, optics and coatings. Titanium nitride (TiN) is an interesting member of the refractory transition metal nitrides family exhibiting chemical and thermal stability. Using density functional theory calculations, the reaction mechanisms of the ALD of TiN using tetra(dimethylamino)titanium (TDMAT) and ammonia as precursors was investigated. The results showed that the mechanism consisted of two reactions: the TDMAT reaction and NH3 reaction. In the TDMAT reaction, the precursor achieved the elimination of dimethylamine via a substitution reaction with the surface amino groups. In the NH3 reaction, the reaction process was complicated. They mainly included exchange reactions between the amino and dimethylamino ligands and coupling reactions forming bridged products and by-products, such as NH3 or HN(CH3)2. As a whole, all of these surface reactions were thermodynamically and kinetically favorable. All these insights into surface reactions of the ALD of TiN provided the guidance for precursor design and the ALD growth of other nitride and titanium-based compounds.

Hydrolysis versus aminolysis of a potential nerve agent tabun: a computational reaction mechanism study

The mechanism for the hydrolysis and aminolysis reactions of potential nerve agent tabun have been investigated both at DFT/M062X level and at ab initio MP2 level of theory. Effect of solvent water has also been incorporated using Minnesota SMD model. Based on leaving groups, there are three probable dissociation pathways of tabun: (1) elimination of HCN, (2) elimination of dimethyl amine and (3) elimination of ethanol. Each of the pathways follows a stepwise neutral route through two transition states. From the mechanism, it has been established that the HCN removal pathway is most favorable than the other two due to greater leaving tendency of the cyanide group. The reaction possesses two four-membered transition state in each path, i.e., for the addition of ammonia/water and for the release of leaving groups. As the four-membered cyclic TSs are not so favorable, the investigated reactions were found quite a bit high energetic. The first addition step of the H2O or NH3 is found as the rate-determining step. The reactivity of ammonia toward tabun has been found highly favorable (by ~ 7.6 kcal mol−1) than the water. This can be easily explained using the fact that the nucleophilicity of NH3 is higher than the H2O. Further, we have seen that water can be a very effective catalyst in the aminolysis reaction as it reduces the barrier of activation of the RDS by ~ 10 kcal mol−1. Self-catalyzed hydrolysis of water has also been performed, and it decreases the activation of ~ 11 kcal mol−1 than the uncatalyzed pathways. The significant reduction of energy of activation takes place due to the formation of six-membered transition states that makes much easier hydrogen transfer compared to the four-membered transition state formed in case of uncatalyzed aminolysis reactions.

Synthesis of 1,2,3-triazoles linked into chains with other carbo- and heterocycles by a reaction between β-azolyl enamines and azides

The reactions of β-azolyl enamines with azides proceeded under solvent-free conditions in the absence of base at 110°С by one of the possible routes, selectively forming 1,4-disubstituted 1,2,3-triazoles. The proposed reaction mechanism includes cycloaddition of the starting reagents, leading to 1,2,3-triazoline intermediates, followed by elimination of dimethylamine and the formation of aromatic triazole ring.

ChemInform Abstract: Formation of Benzocyclobutenes from Substituted Oxocycloocta‐2,8‐diene‐1,2‐dicarboxylates.

AbstractCyclooctadienes (I) and (III) undergo electrocyclization followed by elimination of dimethylamine.

ChemInform Abstract: Synthesis of Novel Pyrazoles Incorporating a Phenothiazine Moiety: Unambiguous Structural Characterization of the Regioselectivity in the 1,3‐Dipolar Cycloaddition Reaction Using 2D HMBC NMR Spectroscopy.

AbstractThe microwave assisted 1,3‐dipolar cycloaddition between compounds (I) or (V) with enaminone (II) provides non‐isolable dihydropyrazole intermediates which undergo elimination of dimethylamine to produce pyrazole derivatives (III) and (VI) with high regioselectivity.

A facile synthesis of tetracyclic benzo-pyridonaphthyridines by domino reaction

A novel methodology for the synthesis of tetracyclic benzo-pyridonaphthyridines, forming a C–C and a C–N bond in concentrated sulfuric acid at 70°C in a one-pot is reported. The key substrates (9a–m) are prepared by reacting 2-chloro-6-(4-fluorophenyl)-4-methylnicotinenitrile (7) with various anilines followed by dimethylformamide dimethylacetal. The domino reaction is initiated by the protonation of the β-carbon of the enamine group in 9a–m and terminated by the elimination of dimethylamine.

Expedient Synthesis of a 72-Membered Isoxazolino-β-ketoamide Library by a 2·3-Component Reaction

An efficient 2·3-component reaction (2·3CR; a 2-component reaction followed, in one pot, by a3-component reaction) is presented for the synthesis of isoxazolino-β-ketoamides. This 2·3CR proceeds by (i) a Meldrum's acid-generated acyl ketene, which is trapped by an amine to form a β-ketoamide intermediate in a 2CR followed, in one pot, by (ii) a Mannich reaction followed by elimination of dimethyl amine·HCl to generate an α,β-unsaturated β-ketoamide dipolarophile that reacts in a nitrile oxide 1,3-dipolar cycloaddition reaction. This one-pot 2·3CR process delivers the targeted isoxazolino-β-ketoamide product. A total of 72 compounds are presented, all of which have been submitted to the NIH Molecular Libraries Small Molecule Repository for high-throughput biological screening.

Exploring rearrangements along the fragmentation pathways of diuron anion: A combined experimental and computational investigation

Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea), a common herbicide from phenyl urea class, was investigated by studying the formation of several negative ions [M−H] − in the gas phase and the fragmentation behaviour of the thermodynamically most probably formed isomeric anions upon linear ion acceleration/collision experiments. The collision induced dissociation experiments (CID) were carried out in a hexapole–quadrupole–hexapole hybrid system coupled to 12 T magnet with infinity ICR cell for high resolution measurements. Two distinctive main pathways were observed in the MS/MS spectrum. Sustained off-resonance irradiation (SORI) experiments inside the ICR cell reinforce the fragmentation channels obtained from linear ion acceleration experiments. The fragmentation pathways were also completely investigated by the use of B3LYP/6-311+G(2d,p)//B3LYP/6-31+G(d) level of theory. Elimination of dimethylamine takes place in a two-step process, by which two successive 1,3 proton shifts occur. The second 1,3 proton shift is concerted with the departure of dimethylamine. The driving force for the (CH 3) 2NH elimination is the formation of isocyanate group. The formed primary product ion can further decompose to release HCl through a new transition state. A stable new aromatic product ion is formed with 10π electrons. Loss of C 3H 5NO neutral from another anionic isomer of the precursor ion was also observed and is characteristic for the amide terminal of the diamide functional group. A concerted mechanism is proposed, by which N–C bond breakage and cyclization of the eliminated neutral fragment C 3H 5NO takes place simultaneously to form 1-methyl-aziridin-2-one.

Identification of Aliphatic and Aromatic Tertiary N-Oxide Functionalities in Protonated Analytes via Ion/Molecule and Dissociation Reactions in an FT-ICR Mass Spectrometer

A mass spectrometric method is presented for the identification of compounds that contain the aliphatic or aromatic N-oxide functional group. This method utilizes gas-phase ion/molecule reactions of tri(dimethylamino)borane (TDMAB), which rapidly derivatizes protonated aliphatic and aromatic tertiary N-oxides, amides, and some amines via loss of dimethylamine in a Fourier transform ion cyclotron resonance mass spectrometer. The mechanism involves proton transfer from the protonated analyte to the borane, followed by addition of the analyte to the boron center and elimination of dimethylamine. The derivatized analytes are readily identified on the basis of their m/z value which is 98 Th (thomson) greater than that of the protonated analyte, and the characteristic boron isotope patterns. SORI-CAD of the product ions (adduct-(CH3)2NH) yields different fragment ions for aliphatic tertiary N-oxides, aromatic tertiary N-oxides, amides, and pyridines. Therefore, these analytes can be identified based on their characteristic fragment ions. This method was tested by examining two drug samples, Olanzapine and Olanzapine-4' N-oxide.

Novel dinuclear dimethylamido-3,5-dimethylpyrazolato and tetranuclear dimethylamido-3,5-dimethylpyrazolato-polyoxo zirconium(iv) complexes. Synthesis and structural characterisation

The dinuclear dimethylamido-tris(3,5-dimethylpyrazolato)-zirconium(IV) complex [Zr(3,5-Me2Pz)3(NMe2)]2 1 is prepared by treatment of [Zr(NMe2)4] with 3 equivalents of 3,5-dimethylpyrazole (3,5-Me2PzH) with elimination of dimethylamine. When [Zr(NMe2)4] reacted with 2 equivalents of 3,5-Me2PzH, the bis(dimethylamido)-bis(3,5-dimethylpyrazolato)zirconium(IV) compound [Zr(3,5-Me2Pz)2(NMe2)2]2 2 is obtained. Hydrolysis of [Zr(3,5-Me2Pz)3(NMe2)]2 in wet toluene affords the tetranuclear oxo compound [Zr4(eta2-3,5-Me2Pz)4(NMe2)2(mu3-O)2(mu2-3,5-Me2Pz)4(mu2-NMe2)2] . All synthesised compounds are characterised by NMR spectroscopic and analytical methods. Single crystal X-ray diffraction analysis has established the molecular structures of 1 and 4.

Rate-Dependent Carbon and Nitrogen Kinetic Isotope Fractionation in Hydrolysis of Isoproturon

Stable isotope fractionation permits quantifying contaminant degradation in the field when the transformation reaction is associated with a consistent isotope enrichment factor epsilon. When interpreted in conjunction with dual isotope plots, isotope fractionation is also particularly useful for elucidating reaction mechanisms. To assess the consistency of epsilon and dual isotope slopes in a two-step reaction, we investigated the abiotic hydrolysis of the herbicide isoproturon (3-(4-isopropylphenyl)-1,1-dimethylurea) using a fragmentation method that allows measuring isotope ratios in different parts of the molecule. Carbon and nitrogen position-specific isotope fractionation, as well as slopes in dual isotope plots, varied linearly with rate constants k(obs) depending on the presence of buffers that mediate the initial zwitterion formation. The correlation can be explained by two consecutive reaction steps (zwitterion formation followed by dimethylamine elimination) each of which has a different kinetic isotope effect and may be rate-limiting. Intrinsic isotope effects for both steps, extracted from our kinetic data using a novel theoretical treatment, agree well with values computed from density functional calculations. Our study therefore demonstrates that more variable isotope fractionation may be observed in simple chemical reactions than commonly thought, but that consistent epsilon or dual isotope slopes may nonetheless be encountered in certain molecular fragments.

Studies with enamines: Reactivity of N,N‐dimethyl‐N‐[(E)‐2‐(4‐nitrophenyl)‐1‐ethenyl]amine towards nitrilimine and aromatic diazonium salts

Abstractmagnified imageIn the presence of triethylamine, cycloaddition reaction of enamine 1 with hydrazonoyl halides 2 followed by dimethylamine elimination was achieved, yielding the corresponding 1,3,4‐trisubstituted pyrazoles 4. Coupling of enamine 1 with aromatic diazonium salts afforded 2‐(arylhydrazono)‐2‐(4‐nitrophenyl)acetaldehyde 9 in good yield. Refluxing the phenyl hydrazone 9a with chloroacetone in ethanol in the presence of triethylamine afforded 1,3,5‐trisubstituted pyrazole 12a, formed via intermediate 11a. Reaction of 9a with hydroxylamine hydrochloride in ethanol in the presence of anhydrous sodium acetate yielded oxime 13a which was irradiated in a microwave oven in the presence of acetic acid to afford a mixture of 15a and 16a.

Internal Alkene Hydroaminations Catalyzed by Zirconium(IV) Complexes and Asymmetric Alkene Hydroaminations Catalyzed by Yttrium(III) Complexes

AbstractThe thiophosphinic amide 2 was prepared in 68 % yield by the reaction of 2,2‐dimethyl‐1,3‐propanediamine with diisopropylchlorophosphine followed by the addition of sulfur. Attachment of the proligand 2 to zirconium was achieved by direct metalation with Zr(NMe2)4 in benzene‐d6 or toluene‐d8 to afford complex 3 via elimination of dimethylamine. The neutral Zr(IV) complex 3 has been shown to be an effective precatalyst for intramolecular alkene hydroaminations that provide cyclic amines in good to excellent yields. A variety of chiral ligands (20, 22, 24, and 25–30) were prepared for asymmetric internal alkene hydroaminations. Metalation of chiral ligands to yttrium was accomplished with Y[N(TMS)2]3 in benzene‐d6 or toluene‐d8 to give complexes. Treatment of 7 with 5 mol % of 33 in benzene‐d6 (25 °C, 18 h) or toluene‐d8 (25 °C, 15 h) afforded 2,4,4‐trimethylpyrrolidine 14 in 95 % yield (61 % ee).

An effective procedure for the preparation of 3-substituted-4- or 6-azaindoles from ortho-methyl nitro pyridines

3-Substituted-4- and 6-azaindoles were prepared from ortho-methyl-nitropyridines in a practically convenient, one-pot process based on the Leimgruber–Batcho reaction. The procedure comprises a sequence of (a) condensation of an ortho-methyl-nitropyridine with N, N-dimethylformamide dimethyl acetal; (b) alkylation or acylation of the enamine intermediate; (c) reduction of the nitro group to an aniline with in situ cyclization and elimination of dimethylamine to generate the 3-substituted azaindole heterocycle.

Regiospecific one-pot synthesis of pyrimido[4,5-d]pyrimidine derivatives in the solid state under microwave irradiations

Electron rich 6-[(dimethylamino)methylene]amino uracil 1, undergoes [4+2] cycloaddition reactions with various in situ generated glyoxylate imine and imine oxides 6 to provide novel pyrimido[4,5-d]pyrimidine derivatives of biological significance, after elimination of dimethylamine from the (1:1) cycloadducts and oxidative aromatisation. This procedure provides a convenient method for the direct synthesis of pyrimido[4,5-d]pyrimidines in excellent yields when carried out in the solid state and under microwave irradiations.

Facile and Versatile Annulation of the Imidazole Ring: Single and Sequential Cyclization Reactions of Fischer Carbene Complexes with 1,4‐Diazafulvenes

We examined the reactivity of dimethylaminodiazafulvene 1 toward Fischer alkenylcarbene 2 and alkynylcarbene 3 complexes. Diazafulvene 1 reacts with alkenylcarbenes 2 through a formal [6+3] heterocyclization in a regio- and stereoselective manner to afford dihydroimidazo[1,2-a]pyridines 4. Acid-promoted dimethylamine elimination in compound 4 c gives rise to the aromatic imidazo pyridine 5. A likely mechanism for this reaction is a 1,2-nucleophilic addition/[1,2]-shift metal-promoted cyclization sequence. On the other hand, diazafulvene 1 and alkynyl carbenes 3 undergo a [6+2] cyclization to afford pyrrolo[1,2-a]imidazole carbene complex 6 that can be readily oxidized to the corresponding esters 7. When enynylcarbenes 3 e-i are treated with diazafulvene 1, consecutive and diastereoselective [6+2]/cyclopentannulation cyclization reactions take place affording new polycyclic complex systems 8, 9, and 12 that can be appropriately demetallated to the corresponding imidazole-based polyfused systems 10, 11, and 13 respectively. Finally, enynylcarbenes 3 d,f undergo consecutive [6+2]/[5+1] cyclization reactions with diazafulvene 1 and tBuNC, respectively, to yield tetracyclic adducts 14 and 15. All these processes result in high yields and provide a route to the preparation of imidazopyridines and pyrroloimidazoles as well as other polycyclic molecules that contain imidazole groups, which are interesting from a pharmacological and biological point of view.

An Efficient Preparation of β‐Dimethylaminovinyl Sulfone and Sulfoximide, and Investigation of Their Reactivity as Dipolarophiles.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Studies on 6‐[(Dimethylamino)methylene]aminouracil: A Facile One‐Pot Synthesis of Novel Pyrimido[4,5‐d]pyrimidine Derivatives.

AbstractFor Abstract see ChemInform Abstract in Full Text.

An efficient preparation of β-dimethylaminovinyl sulfone and sulfoximide, and investigation of their reactivity as dipolarophiles

A simple reaction affording (E)-1-dimethylamino-2-phenylsulfonylethylene, and S-((E)-2-(N',N'-dimethylamino)ethenyl)-S-phenyl-N-(p-tolylsulfonyl) sulfoximide in high yields is described. A reversal in regioselectivity was observed when the β-dimethylaminovinyl sulfone was employed as a dipolarophile in cycloadditions with nitrile oxides. The sulfone gives rise mainly to 4-substituted isoxazoles, after elimination of dimethyl amine. In comparison, phenyl vinyl sulfone cycloadds to give 5-substituted isoxazolines. Although not showing comparable dipolarophilic activity in reactions with nitrile oxides and nitrile imides, the β-dimethylaminovinyl sulfoximide was easily converted to S-((E)-(3-ethoxycarbonyl)prop-2-enyl)-S-phenyl-N-(p-tolylsulfonyl) sulfoximide. This allylic sulfoximide cycloadds in good yield to both benzonitrile oxide and diphenylnitrile imide, but no stereoselectivity was observed in the process; and only modest regioselectivity was detected in the case of benzonitrile oxide.