Sn(OTf)2 catalysed regioselective styrene oxide ring opening with aromatic amines

Sn(OTf)₂ is an efficient and versatile catalyst for the highly regioselective opening of styrene oxide with aromatic amines, which allowed for the preparation of fourteen 2-arylamino-2-phenylethanols, some of them described here for the first time (6g, 6i, 6j, 6k and 6m). Sn(OTf)₂ also catalyses the opening of styrene oxide with aliphatic amines in moderate to high yields but with a lower degree of regioselectivity. 2-Akylamino-1-phenylethanols are the predominant products when moderate to high regioselectivity is observed (compounds 4b, 4c and 4d). This is the first report of the use of Sn(OTf)₂ to catalyse the opening of an epoxide by aliphatic amines.     

Catalytic guanylation of aliphatic,aromatic, heterocyclic primary and secondary amines using nanocrystalline zinc(II) oxide

Nanocrystalline ZnO was found to be a highly efficient heterogeneous catalyst for the guanylation of amines with various carbodiimides to afford N,N′,N″-trisubstituted guanidines in excellent yields. Structurally divergent aliphatic, aromatic, heterocyclic primary and secondary amines were converted to the corresponding N,N′,N″-trisubstituted guanidines using optimal conditions. The catalyst was easy to handle even under atmospheric conditions and can be easily recovered by centrifugation and reused for five cycles with consistent activity.     

Beckmann and cyclization reactions of δ-oxo-α,β-unsaturated ketoximes obtained from pyrylium salts and hydroxylamine. formation of 2-aryl(or alkyl)amino-4,6-disubstituted pyrylium salts

The reaction of 2,4,6-trisubstituted pyrylium salts 1 with hydroxylamine gave regio- and stereo-selectively 1,3,5-trisubstituted 2-cis-pentene-1,5-dione 1-oximes 4. On cyclization, 3,5,5-trisubstituted 2-isoxazolines 6 and 2,4,6-trisubstituted pyridine 1-oxides 5 were obtained, originating in the antilsyn stereoisomers of oxime 4, respectively. Beckmann reaction of keto-ketoximes 4 with thionyl chloride unexpectedly gave 2-aryl (or alkyl) amino-4,6-di-substituted pyrylium salts 7, the first example of rearrangement/cyclization involving carbonylic oxygen as terminator. Crystallographic data are provided for (Z)-N-t-butyl-3,6,6-trimethyl-2-heptenecarboxamide 13b.     

Diastereoselective synthesis of multisubstituted isoindolines via Sequential Ugi and aza-Michael addition reaction

A new efficient and diastereoselective synthesis of multisubstituted isoindolines with two stereogenic centers via sequential Ugi/aza-Michael addition reaction was developed. Ugi-3CR of aldehydes 1, amines 2 and isocyanates 3 in the presence of catalytic amount of H₃PO₄ produced intermediates 4, which were then transformed to isoindolines 5 with good 1,3-trans diastereoselectivity in the presence of K₂CO₃ by intramolecular aza-Michael addition. Sequential Ugi-azide and aza-Michael addition reaction of aldehydes 1, amines 2 and trimethylsilyl azide 6 also produced 4-tetrazolyl substituted isoindolines 8 with good 1,3-trans diastereoselectivity in the presence of potassium carbonate.     

Diastereoselective LiAlH4 reduction of chiral ketone hydrazones derived from (R)-(–)-2-aminobutan-1-ol

Various chiral N,N-dialkylhydrazines were prepared in four to five steps from (R)-(–)-2-aminobutan-1-ol 6. They reacted with various prochiral ketones, thus giving the corresponding hydrazones. Reduction of the latter by means of LiAlH₄ afforded N,N,N′-trisubstituted hydrazines whose d.e.s were in the range 43–100%. Interestingly, LiAlH₄ reduction of the four N-trifluoroethylhydrazones 34 and 38–40 yielded the hydrazines 46 and 48–50, respectively, and with d.e.s=100% by ¹H and ¹³C NMR.     

Reactions of 4-substituted 5H-1,2,3-dithiazoles with primary and secondary amines: fast and convenient synthesis of 1,2,5-thiadiazoles, 2-iminothioacetamides and 2-oxoacetamides

The treatment of 5H-1,2,3-dithiazole-5-thiones 1 in chloroform under reflux and 5H-1,2,3-dithiazol-5-ones 2 in THF at room temperature with primary aliphatic amines and benzylamine afforded 1,2,5-thiadiazole-3(2H)-thiones 3 and 1,2,5-thiadiazol-3(2H)-ones 6, respectively. The structure of dithiazolone 3f was confirmed by X-ray diffraction analysis. The reaction of dithiazolone 2e bearing an electron-donating methyl group in the 4-position gave 2-oxoacetamide 7e in high yield. The reaction of thiones 1 with secondary aliphatic amines in DMSO yielded 2-iminothioacetamides 8 in moderate yields together with elemental sulfur. Interestingly, the treatment of dithiazolones 2 with secondary amines under the same conditions afforded 2-oxoacetamides 9—the products of the hydrolysis of corresponding imino derivatives 10, which was isolated as 10b. A general mechanism was proposed for the formation of the products.     

Studies on organophosphorus compounds: Thiation of 3,1-benzoxathian-4-ones. New routes to 1,2-benzisothiazole-3(2H)-thiones and 3H-1,2-benzodithiol-3-imines

3,1-Benzoxathian-4-ones, 2, when heated with 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2, 4-disulfide, 1, or with P₄S₁₀ give one or more of the following products 3,1-benzoxathian-4-thione, 3, 1,3-benzodithian-4-one, 4, 1,3-benzodithian-4-thione, 5, and 3H-1,2-benzodithiole-3-thione, 6. Compounds 2, when heated with primary and secondary amines and with hydrazines, give 2-mercaptobenzamides, 7, and 2-mercaptobenzohydrazides, 8, or their corresponding disulfides, 7' and 8'. 3H-1, 2-Benzodithiol-3-immes, which are in equilibrium with 1,2-benzisothiazole-3(2H)-thiones, (9A ? 9B), are prepared by two new routes (a) by allowing 3 or 5 to react with primary amines or hydrazines, (b) by allowing 7, 8, 7' or 8' to react with 1.     

Synthesis, structure and electrochemical properties of N-substituted diiron azadithiolates as active site models of Fe-only hydrogenases

As biomimetic models for the active site of Fe-only hydrogenases,six new N-substituted diiron azadithiolates (ADT) were prepared.Treatment of CH₂Cl₂ solutions of primary amines RNH₂ with paraformaldehyde followed by an excess of SOCl₂ gave N,N-bis(chloromethyl)amines RN(CH₂Cl)₂ (1,R = CH₂CO₂Et;2,C₆H₄C(O)Me-p;3,C₆H₄CO₂Me-p;4,C₆H₄SCN-p) in 30-90% yields.Further treatment of the chloromethylated amines 1-4 with (μ-LiS)₂Fe₂(CO)₆ in THF resulted in formation of the corresponding N-substituted ADT-type models [(μ-SCH₂)₂NR]Fe₂(CO)₆ (5,R = CH₂CO₂Et;6,C₆H₄C(O)Me-p;7,C₆H₄CO₂Me-p;8,C₆H₄SCN-p) in 24-75% yields.Also prepared were the N-substituted models [(μ-SCH₂)₂NC(O)CH₂C₁₀H₇-α]Fe₂(CO)₆ (9) and 1,4-[Fe₂(CO)₆(μ- SCH₂)₂NC(O)]₂C₆H₄ (10) by reaction of CH₂Cl₂ solutions of [(μ-SCH₂)₂NH]Fe₂(CO)₆ with α-C₁₀H₇CH₂COCl and 1,4-C₆H₄(COCl)₂ in 81% and 28% yields, respectively. All the new compounds 1-10 were characterized by elemental analysis and spectroscopy, as well as for 5-7 and 9 by X-ray crystallography. The crystallographic studies indicated that the functionality of 5 attached to the bridged N atom lies in an equatorial position, whereas those of functionalities of 6, 7, and 9 are located in an axial position. This is presumably due to different electronic and steric effects between the N-substituted aliphatic and aromatic functionalities. More interestingly, model 7 has been found to be a catalyst for proton reduction in the presence of either strong acid CF₃CO₂H or weak acid HOAc under electrochemical conditions. In addition, two mechanisms ECCE and EECC are preliminarily suggested for such two electrocatalytic H₂ production processes, respectively.     

Microwave-assisted synthesis of pyrazolo[3,4-d]pyrimidines from 2-amino-4,6-dichloropyrimidine-5-carbaldehyde under solvent-free conditions

The microwave-induced synthesis of pyrazolo[3,4-d]pyrimidines 4 in the reaction of N⁴-substituted-2,4-diamino-6-chloro-5-carbaldehydes 3 with hydrazine is described here. Precursors 3 have been prepared by the mono-amination of 2-amino-4,6-dichloropyrimidine-5-carbaldehyde 2 with aliphatic and aromatic amines. The reaction times with primary amines were relatively shorter than for secondary amines.     

Selective N-methylation of primary aliphatic amines with dimethyl carbonate in the presence of alkali cation exchanged Y-faujasites

The N-methylation of aliphatic amines [XC₆H₄(CH₂)_nNH₂; n=1, X=H (1a), o-MeO (1b), p-MeO (1c); n=2, X=H (2a), o-MeO (2b); 1d: PhCH(Me)NH₂] with dimethyl carbonate (DMC) is efficiently catalysed by NaY faujasite: on condition that CO₂ (a co-product of the reaction) is carefully removed, N-methyl- and N,N-dimethyl-amines (RNHMe and RNMe₂) are obtained in good overall yields (70-90%). Otherwise, in the presence of CO₂, carbamates (RNHCO₂Me) form competitively to a large extent. The reaction probably proceeds through a B_Al2 displacement of the amine on DMC.     

A fluorous tag-bound fluorescence derivatization reagent, F-trap pyrene, for reagent peak-free HPLC analysis of aliphatic amines

We have developed a novel pre-column fluorescence derivatization reagent for amines, F-trap pyrene. This reagent comprises a fluorescent pyrene moiety, an amine-reactive Marshall linker, and a fluorophilic perfluoroalkyl group known as fluorous tag. When the reagent reacts with aliphatic amines and amino acids to give fluorescent derivatives, the fluorous tag in the reagent is eliminated simultaneously. Therefore, excess unreacted reagents in the derivatization reaction solution still have the fluorous tag and could be removed by fluorous solid-phase extraction selectively before high-performance liquid chromatography (HPLC) analysis. By using this reagent, 13 kinds of aliphatic amine (C₂–C₁₆) derivatives can be separated within 40 min by reversed-phase HPLC with gradient elution. In this chromatogram, unreacted reagents peak at around 28 min, greatly decrease after fluorous solid-phase extraction, and do not interfere with the quantification of each amine. The detection limits (S/N = 3) for examined aliphatic amines are 3.6–25 fmol per 20 μL injection. We have also applied this reagent successfully to the amino acid analysis.

Adsorption of long-chain aliphatic amines—components of corrosion inhibitors

Adsorption of certain long-chain aliphatic amines with 6–18 carbon atoms is studied on a stationary mercury drop electrode using the impedance method. It is found that adsorption of amines with C₆–C₁₂ results in the formation of an adsorption layer with the limiting capacitance of about 5 μF/cm². In the case of amines with C₁₄–C₁₆, the limiting capacitance is approximately 0.5–0.7 μF/cm². The most probable reason for such abrupt decrease in the adsorption layer capacitance is the formation of condensed layers of adsorbate molecules at the electrode surface. The adsorption parameters are calculated for hexylamine. The surface activity is estimated for amines with 10–14 carbon atoms in their chains.     

Reaction of alkyl- and arylamines with 2-(hydroxyimino)-3-oxobutanal

The condensation of 2-(hydroxyimino)-3-oxobutanal with primary aliphatic amines, cyclohexanamine, and amines containing an adamantane fragment afforded 4-(alkylamino)- and 4-(cyclohexylamino)-3- nitrosobut-3-en-2-ones. Analogous reaction with substituted anilines RC₆H₄NH₂ (R = H, 4-Me, 4-OMe, 4-NH₂, 4-Br, 4-I, 3-NO₂) led to the formation of 4-aryl-3-hydroxyiminobutan-2-ones.     

Microwave assisted synthesis of 3-benzazepin-2-ones as building blocks for 2,3-disubstituted tetrahydro-3-benzazepines

Microwave assisted condensation of primary amines with keto acids 1a–c provided directly 3,4-disubstituted 1,3-dihydro-3-benzazepin-2-ones 2. Whereas small amine size, such as NH₃ afforded high yields of secondary lactams 2a, 2d, and 2g, primary amines with larger substituents in α-position led to lower yields of 2 or even to regioisomeric indanone derivatives 4. However, subsequent alkylation of 2a, 2d, and 2g with various alkyl halides provided the corresponding N-substituted 3-benzazepin-2-ones 2 in good yields. Hydrogenation of 2 followed by BH₃ reduction led to 3-benzazepines 9. 3-Benzyl-2-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine (9c) reveals high σ₁ affinity and selectivity over σ₂ and NMDA receptors.     

Features and applications of reactions of α,β-unsaturated N-acylbenzotriazoles with amino compounds

Promoted by triethylamine, α,β-unsaturated N-acylbenzotriazoles reacted with amino compounds in a variety of ways. Thus, N-cinnamoylbenzotriazoles reacting with aromatic amines afforded novel addition products β-benzotriazolyl amides 3, which might be normally formed from the alternative but unknown 1,4-addition of benzotriazole to N-cinnamoylamides. The type 3 compounds could also result from the reaction between N-crotonoylbenzotriazole and aliphatic amines. However, normal 1,4-addition could occur between α,β-unsaturated aliphatic N-acylbenzotriazoles and aromatic amines, leading to β-amino N-acylbenzotriazoles 4 in good yields. In addition, exclusive 1,2-addition of aliphatic amines to N-cinnamoylbenzotriazoles gave excellent yields of cinnamides 5. Accordingly, three possible routes were proposed to rationalize the formation of compounds 3-5. Finally, with o-phenylenediamine and o-aminothiophenol as the substrates, the 1,4- and 1,2-addition to α,β-unsaturated N-acylbenzotriazoles could take place concurrently and the corresponding heterocycles 1,5-benzodiazepine-2-one and 1,5-benzothiazepine-4-one were constructed, respectively.     

One-pot synthesis of α-aminophosphonates catalyzed by antimony trichloride adsorbed on alumina

SbCl₃ adsorbed on Al₂O₃ is found to be an efficient and recyclable catalyst in promoting three-component coupling reactions of aldehydes (aromatic and aliphatic), amines (aryl amines, aliphatic amines and esters of S-α-amino acids) and dialkylphosphites to afford the corresponding α-aminophosphonates in high yields. The ethyl ester of S-phenylalanine was observed to yield the corresponding α-aminophosphonate with S,S-diastereoisomer formed in dominance over the S,R-diastereoisomer.     

Si-Chlor-oktamethyl-cyclotrisilazan und seine Derivate

The title compound1 b, formed by equation (1), reacts with different amines and metallated amines via equations (2), (3) and (4) to give the compounds2–7, partially with the formerly unknown SiN-skeletons (NSi)₃NSi₂ and (NSi)₃N(SiN)₃.     

Assembly of two layered cobalt-molybdenum phosphates: Changing interlayer distances by tuning the lengths of amine ligands

By using amines with different lengths, two layered cobalt-molybdenum phosphates with different interlayer distances, (C₂N₂H₁₀) [HCo(H₂O)₂P₂MoO₁₀] (1), and (C₃N₂H₁₂)₄{Co₃ [P₄Mo₆O₂₆(OH)₅]₂}· 5H₂O (2), have been hydrothermally synthesized and characterized. In compound 1, the H₂en direct the [CoMoP₂] clusters to form a layered framework. By changing the lengths of protonated organic amines (H₂en to 1, 3-H₂pn), compound 2 is obtained, in which the sandwich-shaped [Co (Mo₆P₄)₂] clusters are linked by tetrahedrally coordinated cobalt into a layered framework. With the lengths of protonated organic amines increasing, the interlayer distances in compound 2 become larger. This work successfully demonstrates that tuning the lengths and conformation of the protonated organic amines can provide a facile route for the formation of organically templated inorganic open-framework materials. Additionally, susceptibility measurement shows that the two compounds both exhibit antiferromagnetic interactions.     

Water-promoted one-pot vinylogous Mannich-type reaction of trimethylsilyloxyfuran

Water, produced in situ during the formation of imines from aldehydes 1 and amines 2, is employed to promote the one-pot Mannich reaction of trimethylsilyloxyfuran 3a without addition of extra solvent or catalyst. This clean and quick reaction allows the obtention of a series of 5-substituted γ-butenolides 4 with good yields and modest diastereomeric ratio. A large panel of substituents is tolerated ranging from aliphatic chains to aromatic or heteroaromatic rings.     

Enamine chemistry—XXV: Reduction of enaminones by LiAlH4 and NaBH4. Synthesis of α,β-unsaturated aldehydes

Cyclohexanone, 2-methyl-cyclohexanone and 4-methyl-cyclohexanone, 1, were transformed into the enaminones 4a–4e by the following two routes: (A): Acylation of the enamines, 2, derived from 1 and secondary amines (pyrrolidine, morpholine and piperidine) by ethyl chloroformate, and (B): Condensation of 1 with diethyl oxalate, giving the β-ketoesters 3, followed by reaction with the secondary amines. Ethyl 2(-1-pyrrolidinyl)-1-cyclopentene-1-carboxylate, 4f, and methyl 3-(1-pyrrolidinyl)-2-butenoate, 4g, were prepared from ethyl 2-oxo-1-cyclopentanecarboxylate and ethyl 3-oxo-butanoate, respectively, by condensation with pyrrolidine. Reduction of 4a by LAH afforded 1-cyclohexen-1-carboxaldehyde, 5a, 1-cyclohexene-1-methanol, 6a, and 1-(1-cyclohexene-1-methyl)pyrrolidine, 7a, in yields depending on the molar ratio of LAH/4a. Reduction of 4f by LAH gave cyclopentene-1-methanol, 6b, 1-(1-cyclopentene-1-methyl)pyrrolidine, 7b, and ethyl-2(1-pyrrolidinyl)-1-cyclo-pentanecarboxylate, 8b. Compound 4g, when reduced with LAH, yielded methyl 3-(1-pyrrolidinyl) butanoate, 8c (main product) and 1-(2-butenyl)pyrrolidine, 7c (minor). Reduction of 4 by NaBH₄ afforded exclusively the saturated β-aminoesters, 8 in high yields. The reductions with LAH and NaBH₄ are rationalized in terms of the HSAB principle.