Alkyl Methyl Ketones Research Articles

AcOH-Catalyzed Rearrangements of Benzo[e][1,4]diazepin-2(and 3)-ones: Easy Access to 1,4-Dihydroquinazolines and Their Condensed Analogues.

Presented herein is a novel synthesis of new 2-(quinolin-4-yl)-1,4-dihydroquinazoline systems 8, in which the acid-catalyzed rearrangement of spiro[benzo[e][1,4]diazepine-3,4'-quinolin]-2(1H)-ones generated in situ from 3-(2-aminophenyl)-5H-benzo[e][1,4]diazepin-2(1H)-ones 6 with acetone and alkylmethyl ketones has been realized as an important step. An attempt to synthesize isomeric 2-(2-aminophenyl)-5H-benzo[e][1,4]diazepin-3(4H)-one 6'a by hydrolysis of the corresponding N-{2-[5H-benzo[e][1,4]diazepin-3(4H)-on-2-yl]phenyl}acetamide 5'a led to a new heterocyclic system, 6-methyl-8,13-dihydro-13aH-quinazolino[4,3-b]quinazolin-5-ium 13a-carboxylate 14, as a result of an unexpected rearrangement. In addition, it is noteworthy that during the hydrolysis of N-{2-[5H-benzo[e][1,4]diazepin-2(1H)-on-3-yl]phenyl}acetamides 5, the not previously described 14-dihydro-5H-14,5a-(epimino[1,2]benzo)benzo[5,6][1,4]diazepin[2,1-b]quinazolin-6(7H)-ones 7 were unexpectedly obtained.

Enantioselective Synthesis of Biphenyl-Bridged ϵ-Sultams by Organocatalytic Mannich Reactions of Cyclic N-Sulfonylimines with Unactivated Ketones.

A highly enantioselective Mannich reaction of biphenyl-bridged seven-membered cyclic N-sulfonylimines with methyl alkyl ketones is disclosed in this study. The reaction was performed under organocatalysis by using a quinine-derived primary amine as the catalyst in combination with a Brønsted acid as the co-catalyst. High yields (up to 89 %) and excellent enantioselectivities (up to 97 % ee) were observed. For methyl alkyl ketones containing a larger alkyl substituent, specific regioselective addition to the C=N bond is favored at the methyl group. On the contrary, ketones containing a smaller alkyl substituent or hydroxyacetone substrates gave major syn selective Mannich products at the methylene group.

Evaluation of novel solvent extraction systems for Zr/Hf separation with MIBK homologues

Zr/Hf separation has always been a great challenge. Although the methyl isobutyl ketone (MIBK)-thiocyanic acid (HSCN) extraction system selectively extracts Hf over Zr and can realize Zr/Hf separation, it has the following disadvantages: it has a strong smell; it is easy to burn; and there is large loss of extractant during extraction due to the low boiling point (115.7 °C), low flashing point (13 °C), and high solubility of MIBK in water (1.7 % at 25 °C). In this study, Zr/Hf separation performance by MIBK homologues — of which one side of C = O is isopentyl, isohexyl, n-pentyl, n-hexyl or n-heptyl, while the other side are all methyl — were studied and compared with MIBK. Effects of HSCN pre-extraction, HCl concentration, NH4SCN concentration on Zr, Hf extraction and separation performance were investigated. Relationships between methyl alkyl ketone structure and their Zr/Hf separation performance were revealed. A new Zr/Hf separation system MNPK (methyl n-pentyl ketone)-HSCN was found. MNPK has a higher boiling point (151 °C), a higher flashing point (47 °C) and a lower solubility in water (0.43 % at 20 °C) than MIBK. Compared to MIBK, it is safer, more friendly operation environments and less extractant loss during extraction. MNPK has as fast extraction kinetics as MIBK. It also has good anti-emulsification performance. Its maximum βHf/Zr can reach to 12.61. The loaded Zr and Hf in MNPK have very similar stripping behaviors with those loaded in MIBK by HCl and H2SO4 solutions, respectively. MNPK is the most possible candidate to replace MIBK from HSCN media in Zr/Hf separation industry.

Stereoconvergent Direct Ring Expansion of Cyclopropyl Ketones to Cyclopentanones

Recyclization of the ring-opening species of alkyl cyclopropyl ketones to cyclopentanones, which proceeds through an unfavored 5-endo-trig cyclization predicted by Baldwin's rules, is elusive. Herein, as assisted by a strong aryl donor and the Thorpe-Ingold strain on a quaternary cyclopropyl center, stereoconvergent direct ring expansion of cyclopropyl ketones to cyclopentanones promoted by TfOH or BF3·Et2O is described, providing a modular construction of polysubstituted cyclopentanones from aldehydes, alkyl methyl ketones, and α-keto esters within three steps.

I2-catalyzed one-pot oxidative condensation of thiourea, methyl ketones, and aryl thiols into 5-sulfenylated 2-amino-1,3-thiazoles by DMSO.

A one-pot, efficient oxidative-condensation process for constructing both 4-alkyl and 4-aryl-5-(arylthio) thiazol-2-amines using DMSO/I2 is introduced. In this procedure, methyl ketones, thiourea, DMSO, and thiols are reacted together in the presence of molecular I2 at 80°C simply to produce 4-alkyl or aryl-5-(arylthio)thiazol-2-amines due to formation of a C-S bond between thiourea and methyl carbon linked to carbonyl group and the another C-S bond formation between thiol and thiazol ring. Under reaction conditions, both aryl and alkyl methyl ketones including acetophenone and substituted acetophenones also, 2-alkanones such as acetone, 2-butanone, 2-pentanone, and 2-heptanone yield those products successfully.

Internal Rotation of the Acetyl Methyl Group in Methyl Alkyl Ketones: The Microwave Spectrum of Octan-2-one.

Methyl n-alkyl ketones form a class of molecules with interesting internal dynamics in the gas-phase. They contain two methyl groups undergoing internal rotations, the acetyl methyl group and the methyl group at the end of the alkyl chain. The torsional barrier of the acetyl methyl group is of special importance, since it allows for the discrimination of the conformational structures. As part of the series, the microwave spectrum of octan-2-one was recorded in the frequency range from 2 to 40 GHz, revealing two conformers, one with C1 and one with Cs symmetry. The barriers to internal rotation of the acetyl methyl group were determined to be 233.340(28) cm-1 and 185.3490(81) cm-1 , respectively, confirming the link between conformations and barrier heights already established for other methyl alkyl ketones. Extensive comparisons to molecules in the literature were carried out, and a small overview of general trends and rules concerning the acetyl methyl torsion is given. For the hexyl methyl group, the barrier height is 973.17(60) cm-1 for the C1 conformer and 979.62(69) cm-1 for the Cs conformer.

Change in the pH of NaI and methyl alkyl ketone solutions under gamma irradiation

The effects of dissolved chemicals such as NaOH, NaI, methyl ethyl ketone (MEK), and methyl isobutyl ketone (MIBK) on solution pH after gamma irradiation were investigated. Upon irradiation with 1.6–24 kGy of gamma radiation (0.4–6 kGy h−1), the pH of the NaOH solutions decreased, while the OH− consumption increased with increasing initial solution pH. This was attributed to acid–base neutralization between the OH− in the solutions and the acidic species (HO2· and ·NO2) formed by irradiation. The pH of the acidic NaI solution increased after irradiation with 8 kGy dose (at 2 kGy h−1), which was attributed to I− oxidation by the products of water and air radiolysis. The pH values of the MIBK and MEK solutions decreased from 7 to 4.5 or lower upon irradiation with 40 kGy dose (at 10 kGy h−1), which indicates that the alkyl groups of the ketones do not significantly affect the rates of decomposition by irradiation. The pH of the mixed solution of ketone and NaI was in the range of 6.7–6.9 before irradiation but decreased to 4.5 after irradiation with 40 kGy dose. In the mixed solutions, CH3COR and I− competed with each other to contribute to pH change.

C2-Symmetric 1,2-Diphenylethane-1,2-diamine-Derived Primary-Tertiary Diamine-Catalyzed Asymmetric Mannich Addition of Cyclic N-Sulfonyl Trifluoromethylated Ketimines.

A simple chiral primary-tertiary diamine derived from C2-symmetric 1,2-diphenylethane-1,2-diamine as the organocatalyst in combination with the trifluoroacetic acid additive for the asymmetric Mannich reaction of cyclic N-sulfonyl trifluoromethylated ketimines and methyl ketones afforded the desired product with high enantioselectivity (73-96% ee). The reactions proceeded well for a variety of different substituted cyclic N-sulfonyl trifluoromethyl ketimines and various alkyl methyl ketones, providing access to diverse enantioenriched benzo-fused cyclic sulfamidate N-heterocycles bearing a trifluoromethylated α-tetrasubstituted carbon stereocenter. This study also investigated the diastereoselective reduction of the carbonyl group and ring cleavage reduction of the sulfamidate group of the corresponding Mannich product.

Synthesis and structure of sodium 1-alkoxy-1,4-dioxo-2-alkenolates and bis-(4-alkyl(aryl)- 1-oxo-1-alkoxyalkane-2,4-dionato) metals (II) based on them

A priority task in contemporary organic chemistry consists in the synthesis of practically useful metal complexes having carbonyl-containing ligands. The present article details the isolation of several new bis-(4-alkyl(aryl)-1-oxo-1-alkoxyalkane-2,4-dionato) metals (II) via complex formation of metal salts of (zinc (II), copper (II) and nickel (II)) with sodium 1-alkoxy-1,4-dioxo-2-alkenolates obtained by condensation of alkyl (aryl) methyl ketones with dialkyl oxalates in the presence of sodium or sodium hydride as a condensing reagent. The structure of the synthesised sodium oxoenolates and metal complexes was confirmed by spectral analysis methods (IR, NMR 1 H-, NMR 13 C-spectroscopy and mass spectrometry). In the IR spectra of the solid samples of the isolated compounds, stretching vibrations bands of ester carbonyl groups were identified, as well as high-intensity ether bands due to the vibrations of С-О-С bonds. For compounds containing aromatic fragments, bands corresponding to vibrations of monosubstituted benzene rings were found in the IR spectra. The NMR spectra of 1 H of sodium oxoenolates and metal complexes recorded in DMSO-d 6 demonstrated characteristic signals of ethoxy and n - butoxy fragments, methine protons, as well as protons of aromatic rings. Chemical shifts of carbon atoms in the NMR spectra 13 C of sodium oxoenolates correspond well to the reference values. In the mass spectra of synthesised compounds recorded in electrospray mode, signals of protonated and cationised molecules were observed [M+H] + , [M+NH 4 ] + , [M+Na] + , [M+K] + . Using quantum chemical methods, the models of the obtained compounds were constructed along with a calculation of the formation energies and dissociation constants. Optimisation of the geometric parameters of the equilibrium states of sodium oxoenolate and metal complexes was carried out using the following two methods: density functional theory (DFT) and self-consistent field (SCF). The relative formation energies indicate high stability of the synthesised substances, while, according to the data obtained, copper complexes are characterised by greater stability in the gas phase as compared to zinc and nickel.

Biomass‐Derived Aromatics by Solid Acid‐Catalyzed Aldol Condensation of Alkyl Methyl Ketones

AbstractCyclotrimerization of biomass‐based alkyl methyl ketones exhibits great potential as a route to biomass‐derived aromatics by a sustainable valorization of biorefinery streams. In this study, acetone is used as a model reagent to screen solid acid catalysts for the aldol condensation reaction to the aromatic trimer mesitylene. From a broad catalyst screening promising activity is shown by the cation exchange resin Purolite CT275DR, the beta‐zeolite H‐BEA 35, and aluminosilicate Siralox 70/170 HPV which are used to further investigate reaction parameters. Acetone conversion and mesitylene yield increase with temperature and time, while yield of the intermediate mesityl oxide decreases. This effect is also found for higher quantities of catalyst acid sites and is accompanied with an increased side product formation which negatively affects total product selectivity. Analyzing the reaction progress shows a significant drop in catalyst productivity after an initial start‐up phase. This observation is linked to a deactivation of the catalyst which involves water that is formed during the condensation reaction of acetone. Obtained results confirm the general viability of the aromatization of alkyl methyl ketones and can be considered the first step to an alternative sustainable route to biomass‐derived aromatics compared to other currently discussed routes.

An Acetal Acylation Methodology for Producing Diversity of Trihalomethyl- 1,3‑dielectrophiles and 1,2-Azole Derivatives

A series of functionalized 1,1,1-trihalo-4-methoxy-3-alken-2-ones [CX3C(O)CR1=CROMe, where X = F or Cl; R = n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-tridecyl, (CH2)2CH=C(Me)2, (CH2)2Ph, (CH2)2-(4-HOC6H4), (CH2)2-(4-MeOC6H4), (CH2)2CO2Me, (CH2)3CO2Me, CH(SMe)CH3, CH2(2-MeOC6H4), and R1 = H, and R = H and R1 = n-decyl] were synthesized from respective alkyl methyl ketones or aldehyde via acetal acylation using trifluoroacetic anhydride and trichloroacetyl chloride. 1,1,1-Trihalo-4-methoxy-3-alken-2-ones with acid-compatible substituents were easily hydrolyzed to respective trihalomethyl-1,3-diketones. The 1,1,1-trihalo-4-methoxy-3-alken-2-ones and/or respective trihalomethyl-1,3-diketones were reacted regiospecifically with hydroxylamine hydrochloride, leading to isoxazole derivatives, and with hydrazines, leading to respective 1H-pyrazole derivatives. The structures of all compounds were assigned based on nuclear magnetic resonance (NMR) and mass spectrometric data. This method represents an efficient pathway for the regioselective trihaloacetylation of asymmetrically substituted alkyl methyl ketones and highly self-condensing aldehydes. Moreover, this approach allows the introduction of biologically recognizable moieties, such as those from levulinic acid, sulcatone (prenyl), benzylacetone, anisylacetone, and raspberry ketone, as synthetic molecular targets.

Fungal Dirigent Protein Controls the Stereoselectivity of Multicopper Oxidase-Catalyzed Phenol Coupling in Viriditoxin Biosynthesis.

Paecilomyces variotii produces the antibacterial and cytotoxic ( M)-viriditoxin (1) together with a trace amount of its atropisomer ( P)-viriditoxin 1'. Elucidation of the biosynthesis by heterologous pathway reconstruction in Aspergillus nidulans identified the multicopper oxidase (MCO) VdtB responsible for the regioselective 6,6'-coupling of semiviriditoxin (10), which yielded 1 and 1' at a ratio of 1:2. We further uncovered that VdtD, an α/β hydrolase-like protein lacking the catalytic serine, directs the axial chirality of the products. Using recombinant VdtB and VdtD as cell-free extracts from A. nidulans, we demonstrated that VdtD acts like a dirigent protein to control the stereoselectivity of the coupling catalyzed by VdtB to yield 1 and 1' at a ratio of 20:1. Furthermore, we uncovered a unique Baeyer-Villiger monooxygenase (BVMO) VdtE that could transform the alkyl methylketone side chain to methyl ester against the migratory aptitude.

Iron-Catalyzed Tandem Three-Component Alkylation: Access to α-Methylated Substituted Ketones.

The borrowing hydrogen strategy has been applied in the synthesis of α-branched methylated ketones via a tandem three-component reaction catalyzed by a diaminocyclopentadienone iron tricarbonyl complex. Various alkyl and aromatic methyl ketones underwent dialkylation with various primary alcohols and methanol as alkylating agents in mild reaction conditions and good yields. Deuterium labeling experiments suggested that the benzylic alcohol was the hydrogen source in this tandem process.

Metal-Free and Redox-Neutral Conversion of Organotrifluoroborates into Radicals Enabled by Visible Light.

Converting organoboron compounds into the corresponding radicals has broad synthetic applications in organic chemistry. To achieve these transformations, various strong oxidants such as Mn(OAc)3 , AgNO3 /K2 S2 O8 , and Cu(OAc)2 , in stoichiometric amounts are required, proceeding by a single-electron transfer mechanism. Established herein is a distinct strategy for generating both aryl and alkyl radicals from organotrifluoroborates through an SH 2 process. This strategy is enabled by using water as the solvent, visible light as the energy input, and diacetyl as the promoter in the absence of any metal catalyst or redox reagent, thereby eliminating metal waste. To demonstrate its synthetic utility, an efficient acetylation to prepare valuable aryl (alkyl) methyl ketones is described and applications to construct C-C, C-I, C-Br, and C-S bonds are also feasible. Experimental evidence suggests that triplet diacetyl serves as the key intermediate in this process.

Metal‐Free and Redox‐Neutral Conversion of Organotrifluoroborates into Radicals Enabled by Visible Light

AbstractConverting organoboron compounds into the corresponding radicals has broad synthetic applications in organic chemistry. To achieve these transformations, various strong oxidants such as Mn(OAc)3, AgNO3/K2S2O8, and Cu(OAc)2, in stoichiometric amounts are required, proceeding by a single‐electron transfer mechanism. Established herein is a distinct strategy for generating both aryl and alkyl radicals from organotrifluoroborates through an SH2 process. This strategy is enabled by using water as the solvent, visible light as the energy input, and diacetyl as the promoter in the absence of any metal catalyst or redox reagent, thereby eliminating metal waste. To demonstrate its synthetic utility, an efficient acetylation to prepare valuable aryl (alkyl) methyl ketones is described and applications to construct C−C, C−I, C−Br, and C−S bonds are also feasible. Experimental evidence suggests that triplet diacetyl serves as the key intermediate in this process.

Formation of CH3I in a NaI and methyl alkyl ketone solution under gamma irradiation conditions

We investigated the effects of concentrations of NaI and methyl alkyl ketone on the formation of methyl iodide under gamma irradiation conditions. Without irradiation, the formation of methyl iodide does not occur. For the formation of methyl iodide, the solution pH should be brought to lower than 6 by radiolytic decomposition of ketones and air. At a pH below 6, the iodide was oxidized into iodine, allowing for the formation of CH3I from the reaction of iodine and the CH3 radical. When the concentrations of NaI and methyl alkyl ketone were similar, the concentration of methyl iodide was generally at its highest, and as the gamma dose increased, the concentration of methyl iodide increased.

Regio- and chemoselective rearrangement of terminal epoxides into methyl alkyl and aryl ketones.

The development of the highly active pincer-type rhodium catalyst 2 for the nucleophilic Meinwald rearrangement of functionalised terminal epoxides into methyl ketones under mild conditions is presented. An excellent regio- and chemoselectivity is obtained for the first time for aryl oxiranes.

The Synthesis of 7-Substituted-2,3-dihydropyrido [4,3-d]pyridazine-1,4-diones and 1,4-Dioxo-7-substituted-1,2,3,4-tetrahydropyrido[4,3-d]pyridazine 6-Oxides from Methyl Ketones.

A general four-step transformation of alkyl, cycloalkyl, aryl, and heteroaryl methyl ketones via 3-(dimethylamino)-1-substituted-prop-2-en-1-ones, followed by microwave [2+2] cycloaddition of dimethyl acetylenedicarboxylate, cyclization of (2E,3E)-2-[(dimethylamino)methylene]-3-(2-substituted)succinates with ammonia or hydroxylamine hydrochloride into 2-substituted-pyridine-4,5-dicarboxylates and their N-oxides and final cyclization with hydrazine hydrate into of 7-substituted-2,3-dihydropyrido[3,4-d]pyridazine-1,4-diones and 1,4-dioxo-7-substituted-1,2,3,4-tetrahydropyrido[4,3-d]pyridazine 6-oxides is shown.

Highly Enantioselective Synthesis of 11‐Substituted 10,11‐Dihydrodibenzo[b,f][1,4]thiazepines through a Proline‐Catalyzed Mannich Reaction of Seven‐Membered Cyclic Imines with Ketones

AbstractHighly enantioselective Mannich addition reactions of N,S‐heterocyclic dibenzo[b,f][1,4]thiazepines as seven‐membered cyclic imine substrates with ketones were developed by using proline as an organocatalyst. Substituted dibenzo[b,f][1,4]thiazepines and various unsymmetrical alkyl methyl ketones were used as substrates and optimized reaction conditions offered an efficient method to synthesize optically active 11‐substituted 10,11‐dihydrodibenzo[b,f][1,4]thiazepine derivatives that contained a carbonyl functional group in 91–99 % ee. Furthermore, we found that the reactions could also be performed on a gram scale, whilst maintaining high yields and enantioselectivities. The carbonyl group of the Mannich products also underwent diastereoselective reduction, thus yielding a new hydroxy‐substituted chiral stereogenic center with moderate‐to‐excellent diastereoselectivities, good yields, and without the loss of enantiomeric excess.

Synthesis of 1,3,4,6-tetraoxo compounds

The two-step method of synthesis of 1,3,4,6-tetraoxocompounds with different terminal substituents is developed. By condensation of alkyl methyl ketones with dimethyl oxalate new 1,6-dialkyl-substituted 1,3,4,6-tetraoxohexanes are obtained. The esters of 3,4,6-trioxoalkanoic acids are synthesized by the condensation reaction of alkyl acetates with dialkyl oxalates and alkyl methyl ketones. By the reaction of ethyl acetate with diethyl oxalate and methyl acetate the mixed diester of 3,4-dioxo-1,6-hexanedioic (ketipic) acid has been first prepared. Specific structural features of the synthesized compounds are discussed basing on the data of the IR, NMR, and XRD diffraction (XRD) analysis.