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Sodium silicide Na4Si4 is a reductive and reactive source of silicon highly relevant to designing non-oxidic silicon materials, including clathrates, various silicon allotropes, and metal silicides. Despite the importance of this compound, its production in high amounts and high purity is still a bottleneck with reported methods. In this work, we demonstrate that readily available silicon nanoparticles react with sodium hydride with a stoichiometry close to the theoretical one and at a temperature of 395 °C for shorter duration than previously reported. This enhanced reactivity of silicon nanoparticles makes the procedure robust and less dependent on experimental parameters, such as gas flow. As a result, we deliver a procedure to achieve Na4Si4 with purity of ca. 98 mol% at the gram scale. We show that this compound is an efficient precursor to deliver selectively type I and type II sodium silicon clathrates depending on the conditions of thermal decomposition.

Compounds of Li, Na, K and Ca of a tetradentate amino-bis(phenolato) ligand were prepared. Bimetallic compounds formulated as M2[L](THF)n (where M = Na, n = 1 (1·THF) or Li, n = 1 (2·THF)) were synthesized via the reaction of H2[L] (where [L] = 2-pyridylmethylamino-N,N-bis(2-methylene-4-methoxy-6-tert-butylphenolato) with sodium hydride or n-butyllithium, respectively, in THF. Monometallic complexes MH[L](THF)n (where M = Na, n = 1 (3·THF), Li, n = 0 (4) and K, n = 0 (5)) were obtained by reaction of H2[L] with MN(SiMe3)2 where M = Na, Li, or K. Calcium complex Ca[L](THF) (6·THF) was synthesized in two ways; reaction of Na2[L] with calcium iodide in THF, and reaction of Ca[N(SiMe3)2]2 with H2[L] in toluene. Compounds 1–6 exhibit activity for rac-lactide polymerization under melt and solution conditions. Moderate control of polymer molecular weights was achieved in toluene, whereas polydisperse polymer was obtained under solvent free conditions. MALDI-TOF MS analysis of the polymer end groups revealed a predominantly cyclic nature for the polylactides.

The development of reversible networks in elastomers provided unique inspiration for the design of advanced polymers with excellent properties. In this paper, we adopted an anionic melting method to introduce carboxylate groups into 1,2-polybutadiene (1,2-PB), using maleic anhydride as a modifier, and sodium hydride (NaH), calcium hydride (CaH2), and lithium aluminum hydride (LiAlH4) as metallization reagents. Na-Based, Ca-based, and Li/Al-based ionic bond networks were constructed in the covalently crosslinked 1,2-PB. The effects of the electronegativity and valence of the metal ions on the strength and reversible temperature of the ionic network were studied. Payne effect was shown by rheological tests, demonstrating the interactions between the ionic networks and rubber chains. The reforming temperature for these ionic networks was studied by stress-relaxation analysis, and shape memory experiments were performed based on these temperatures. This concept provides novel inspiration for the design of high-performance and temperature-adaptive elastomers.

Reactions of indigo with quinones in the presence of sodium hydride leads unexpectedly to products containing two indigo subunits; one indigo is featured in a cis configuration and fused via its indole nitrogen atoms to a second indigo at the central C-C bond of the latter. Structural, optical, and redox properties of the new compounds are reported.

An in situ generated zinc ascorbate pre-catalyst for cyclic carbonate (CC) synthesis via CO2 coupling with epoxides under ambient conditions was reported. Spectroscopic measurements indicated that CO2 was inserted into the zinc ascorbate complex through the formation of an activated zinc carbonate catalyst upon abstracting the enediol protons with sodium hydride. The aliphatic diols were not activated under the applied conditions and did not interfere with either the process of cycloaddition or CO2 activation. The catalyst was active against different terminal epoxides, with a conversion of 75 and 85%, when propylene oxide and styrene oxide were used at 20 and 50 °C, respectively under 1 atm CO2 for 17 h, which was considered a good advancement for heterogeneous based catalysis. Moreover, green chemistry principles were applied to ultimately end up with more ecofriendly approaches for the synthesis of CC following a simple balloon technique. Herein, we used zinc as a sustainable metal, together with ascorbic acid as a bio-renewable material in addition to CO2 as a renewable feed-stock. Furthermore, waste prevention was achieved using the reaction side product, viz., NaBr as a co-catalyst.

A new protocol for the dearylation of arylphosphine oxides was developed using sodium hydride (NaH) in the presence of lithium iodide (LiI). The transient sodium phosphinite could be functionalized with a range of electrophiles in a one-pot fashion. MOE (Min. of Education, S’pore) Accepted version

A highly efficient one-pot synthesis of β,β-dihalo-β-nitroethyl alkyl ethers is achieved by the treatment of nitroalkenes with alcohols and N-halosuccinimides in the presence of sodium hydride. The notable advantages of this protocol are that it involves simple experimental manipulations and tolerates a wide range of functional groups. Further transformations of the obtained ethers, such as allylation and conversion to β,β-dihalogenated vinyl ethers, are also investigated.

Dicationic tetranuclear ruthenium octahydride [(Cp*Ru)4H8]2+ (5) with tetrahedral geometry was obtained by reaction of dinuclear ruthenium tetrahydride (Cp*Ru)2(μ-H)4 (1) with an excess of Bronsted acids, such as HBF4·OEt2, in toluene. Monocationic tetraruthenium heptahydride [(Cp*Ru)4H7]+ (7) was obtained by dropwise addition of a diluted acid to a rigorously stirred solution of 1 at ambient temperature. Dication 5 was converted into monocationic heptahydrido complex 7 in high yield by treatment with sodium methoxide or sodium hydride. The direct conversion of 5 into neutral hexahydrido complex (Cp*Ru)4H6 (8) was achieved in a highly efficient manner by treating 5 with LiAlH4 in tetrahydrofuran (THF). The conversion of 5 into 8 was reversible, and the addition of a Bronsted acid to 8 gave 5via the formation of 7 as an intermediate. Tetranuclear complex 8 was directly obtained from 1 by heating it in THF at 70 °C. Complex 8′ and tetraruthenium tetrahydride (CpEtRu)4H4 (10′), where 8′ and 10′ possessed η5-C5EtMe4 ligands instead of Cp* ligands, were mutually related by the elimination/addition of dihydrogen. The structures of 5, 7, 8, and 10′ were determined by X-ray diffraction, and the Ru4 core structure and the coordination mode of hydrido ligands were discussed based on density functional theory (DFT) calculations for model compounds where the methyl groups of Cp* ligands were replaced with hydrogen atoms.

This report describes an unprecedented protocol for the synthesis of N,N′-substituted ureas using a cross-coupling method. Mono substituted ureas were modified by an economically viable and simple method using commercially available isocyanates and sodium hydride as the reagents. In addition, the method involves no expensive metal complexes or catalysts and all reactions are carried out at room temperature. Furthermore, both symmetrical and asymmetrical ureas were successfully obtained in single step reactions with reasonable yields.

Exocyclic enamides have been used extensively in the synthesis of natural products and biologically active substances. A facile and efficient protocol has been developed for the synthesis of a series of new 5-methylenemorpholin-3-one derivatives, which are exocyclic enamides, based on the reactions of trifluoroatrolactamides with propargyl bromide in the presence of sodium hydride. The biological evaluation of these compounds showed that some of them exhibited very good in vitro fungicidal activity against P. oryzae. For example, compounds 2d and 2e gave fungicidal activities of 50% at a concentration of 0.9 μg mL−1, whilst the control compound fenaminstrobin gave 80% activity at the same concentration.

Reaction of Zn(C6F5)2·toluene (two equivalents) with 1,3-dipropoxy-p-tert-butyl-calix[4]arene (L(1)H2) led to the isolation of the complex [{Zn(C6F5)}2L(1)] (1), whilst similar use of Zn(Me)2 resulted in the known complex [{Zn(Me)}2L(1)] (2). Treatment of L(1)H2 with in situ prepared Zn{N(SiMe3)2}2 in refluxing toluene led to the isolation of the compound [(Na)ZnN(SiMe3)2L(1)] (3). The stepwise reaction of L(1)H2 and sodium hydride, followed by ZnCl2 and finally NaN(SiMe3)2 yielded the compound [Zn{N(SiMe3)2}2L(1)] (4). The reaction between three equivalents of Zn(C6F5)2·toluene and oxacalix[3]arene (L(2)H3) at room temperature formed the compound {[Zn(C6F5)]3L(2)} (5); heating of 5 in acetonitrile caused the ring opening of the parent oxacalix[3]arene and rearrangement to afford the complex [(L(2))Zn6(C6F5)(R)(RH)OH]·5MeCN R = C6F5CH2-(p-(t)BuPhenolate-CH2OCH2-)2-p-(t)BuPhenolate-CH2O(-))(3-) (6). The molecular structures of the new complexes 1, 3 and 6, together with that of the known complex 2, whose solid state structure has not previously been reported, have been determined. Compounds 1, 3-5 have been screened for the ring opening polymerization (ROP) of ε-caprolactone (ε-CL) and rac-lactide. Compounds featuring a Zn-C6F5 fragment were found to be poor ROP pre-catalysts as they did not react with benzyl alcohol to form an alkoxide. By contrast, compound 4, which contains a zinc silylamide linkage, was the most active of the zinc-based calix[4]arene compounds screened and was capable of ROP at ambient temperature with 65% conversion over 4 h.

Iminopyrrolyl complexes of sodium were prepared from the reaction of 2-arylformiminopyrrole ligand precursors (aryl = C(6)H(5) (I); 2,6-Me(2)C(6)H(3) (II); 2,4,6-Me(3)C(6)H(2) (III); 2,6-(i)Pr(2)C(6)H(3) (IV)) with one equivalent of sodium hydride. The resulting corresponding compounds 1-4, [{Na(mu(2):kappa(2)N,N'-iminopyrrolyl)}(2n)(OEt(2))(2x)] (nor = 1; x = 0 or 1), were obtained in moderate to high yields and were characterised by NMR spectroscopy, high resolution mass spectrometry and X-ray diffraction, when suitable crystals were obtained. The X-ray structure of compound 1 (n1; x = 0) reveals the formation of a coordination polymer with repeating units consisting of dimers that contain two iminopyrrolyl ligands chelating two sodium atoms, where both pyrrolyl rings exhibit bridging sigma + sigma coordination to the Na atoms within the dimer; the self-assembling of the polymer is established by additional pi-bonds (eta(5)-coordination) of each of the pyrrolyl rings to the sodium atoms of the adjacent dimer units. Conversely, the structure of complex D(IV) (n = x = 1) shows it as one of such dimers capped by two diethyl ether molecules, each coordinated to the sodium atoms (n = 2; x = 1). DFT calculations indicate that the differences between the structures 1-4 of arise from the increasing bulkiness imposed by the corresponding substituents of the iminic aryl groups.

Herein, we describe the solvent-free ball milling Tishchenko reaction. Using high speed ball milling and a sodium hydride catalyst, the Tishchenko reaction was performed for aryl aldehydes in high yields in 0.5 hours. The reaction is not affected by the type of ball bearing used and can be successful when conducted in a liquid nitrogen environment.

Doping NaAlH(4) with Ti-catalyst has produced a promising hydrogen storage system that can be reversibly operated at moderate temperature conditions. Of the various dopant precursors, TiCl(3) was well recognized due to its pronounced catalytic effect on the reversible dehydrogenation processes of sodium aluminium hydrides. Quite recently we experimentally found that TiF(3) was even better than TiCl(3) in terms of the critical hydrogen storage properties of the doped hydrides, in particular the dehydriding performance at Na(3)AlH(6)/NaH + Al step at moderate temperature. We present here the DFT calculation results of the TiF(3) or TiCl(3) doped Na(3)AlH(6). Our computational studies have demonstrated that F(-) and Cl(-) anions differ substantially from each other with regard to the state and function in the doped sodium aluminium hydride. In great contrast to the case of chloride doping where Cl(-) anion constitutes the "dead weight" NaCl, the fluoride doping results in a substitution of H(-) by F(-) anion in the hydride lattice and accordingly, a favorable thermodynamics adjustment. These results well explain the observed dehydriding performance associated with TiF(3)/TiCl(3)-doping. More significantly, the coupled computational and experimental efforts allow us to put forward a "functional anion" concept. This renews the current mechanism understanding in the catalytically enhanced sodium alanate.

6-Nitroquinoline 6 undergoes direct cyclocondensation with aromatic aldehyde hydrazones 9 in the presence of sodium hydride in DMF at low temperature, giving the corresponding 3-aryl-1H-pyrazolo[3,4-f]quinolines 10 and/or 3-aryl[1,2,4]triazino[6,5-f]quinolines 11 in low to moderate yield. With aromatic keto hydrazones 7, 3,3-disubstituted 2,3-dihydro[1,2,4]triazino[6,5-f]quinoline-4-oxides 8 are obtained in moderate to good yield. The mode of cyclocondensation is considerably dependent on the electronic nature of a ring substituent of the aromatic hydrazones; electron-donating substituents favor the formation of 11, while electron-withdrawing substituents work favorably for the formation of 10. Monocyclic nitroarenes 15 react similarly with 4-nitrobenzaldehyde hydrazone 9a to give another type of cyclocondensation product, 3-aryl-1H-indazoles 16, in moderate yield. In contrast, nucleophilic substitution of a ring hydrogen atom takes place with 4-methylbenzaldehyde hydrazone 9f to yield N-arylated hydrazone 22b, which, however, fails to cyclize to 16 under the conditions employed. The reaction has been suggested to proceed through the initial attack of a hydrazone anion on the position adjacent to the nitro group, followed by migration of an ipso hydrogen atom to the nitro group in the Meisenheimer intermediate 18. The resulting N2-arylated hydrazone anion would undergo ring closure via either addition to the nitroso group or displacement of this moiety, eventually leading to the fused aza-arenes 8, 10/11, 13 or 16.

A simple method for the synthesis of both cis-2-vinylaziridines and 3-pyrrolines from common intermediate (Z)-4-(N-arylsulfonyl)amino-4-alkylbut-2-en-1-ols, is described. Palladium(0)-catalyzed reactions of methyl carbonates of the N-protected (Z)-4-amino-4-alkylbut-2-en-1-ols yield predominantly cis-3-alkyl-2-vinylaziridines. Alternatively, upon exposure to sodium hydride, methanesulfonates derived from N-protected (Z)-4-amino-4-alkylbut-2-en-1-ols give exclusively the corresponding 3-pyrrolines in high yields. A synthesis of biologically important (S)-3,4-dehydroproline is also presented.

The synthesis of (RS)-2-amino-3-(5-cyclopropyl-3-hydroxyisoxazol-4-yl)propionic acid 6, an analogue of the AMPA receptor agonist (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)-propionic acid, AMPA, 3 is described. Compound 6 has been studied in vitro in radioligand binding and electrophysiological test systems and shown to be a specific AMPA receptor agonist equipotent with AMPA. The synthesis of 6 was based on 5-cyclopropyl-3-hydroxyisoxazole 8, which was converted into the intermediate 4-bromomethyl-5-(3-bromopropyl)-2-methoxymethyl-2,3-dihydroisoxazol-3-one 9 by opening of the cyclopropane ring. Based on 1H and 13C NMR data, this conversion has been shown to proceed stepwise, the progression of the different steps being dependent on the concentration of the hydrobromic acid medium, reaction time, and temperature. An acetamidomalonate group has been regiospecifically substituted for the allylic bromine atom of 9 to give 10, and treatment of 10 with sodium hydride gave compound 11 containing a cyclopropyl group, reformed by cyclization of the 3-bromopropyl substituent of 10. Compound 11 has been fully deprotected by treatment with aqueous trifluoroacetic acid to give 6.

Treatment of arachno-4-CB8H14 with sulfur and triethylamine in chloroform has produced the new tenvertex carbathiaborane arachno-6,9-CSB8H12, which has been used for the preparation of a series of further carbathiaborane compounds. Deprotonation with sodium hydride or 1,8-bis(dimethylamino)-naphthalene generates the [arachno-6,9-CSB8H11]– anion. Thermolysis of the sodium salt of this anion, followed by acidification, results in comproportionation to give nido-7,9-CSB9H11 and arachno-4,6-CSB7H11. Alternatively, oxidation by acetone yields the [nido-6,9-CSB8H9]– anion. Degradation of this latter anion with concentrated hydrochloric acid leads to arachno-4,6-CSB7H11. Deprotonation of this neutral carbathiaborane with sodium hydride in ether, followed by degradation by aqueous acetone of the [arachno-4,6-CSB7H10]– anion generated in situ, gives the [hypho-7,8-CSB6H11]– anion. This has been methylated by methyl iodide to afford neutral 8-Me-hypho-7,8-CSB6H11. The unambiguous cluster constitutions of all compounds isolated have been established by 1H and 11B NMR spectroscopy and mass spectrometry.

1-Aryl-α,β-unsaturated ketones were directly aziridinated, N-unsubstituted, in a one-pot reaction with satisfactory yields by N,N′-diamino-1,4-diazoniabicyclo[2.2.2]octane dinitrate, a nitrogen–nitrogen ylide precursor, in the presence of sodium hydride.

A new general method for a one-carbon intercalation of γ-lactones δ-lactones and δ-lactones to Iµ-lactones in three steps involving a selective β-scission of the alkoxyl radicals as the key step is described. The reactions of γ- and δ-lactones with lithioalkyl acetate gave an equilibrated mixture of alkyl (2-hydroxytetrahydrofuran-2-yl)acetates and alkyl (2-hydroxytetrahydropyran-2-yl)acetates, as well as their ring-opened isomers in 62–95% yields, respectively. The photolysis of the hypoiodites of these lactols in benzene containing mercury(II) oxide and iodine with Pyrex-filtered light resulted in a selective endocyclic β-scission of the corresponding alkoxyl radicals to give alkyl iodoalkyl propanedioates in 33–70% yields. Treatment of the iodoalkyl propanedioates with tetraethylammonium bromide and sodium hydride gave alkyl 3,4,5,6-tetrahydro-2-oxo-2H-pyran-3-carboxylates or alkyl 2,3,4,5,5a,6,7,8,9,9a-decahydro-2-oxobenz[1]oxepine-3-carboxylase in 61–81% yields. On the other hand, successive treatment of ω-iodoalkyl propanedioates with tetraethylammonium bromide–sodium hydride and then benzyl bromide gave a α-disubstituted δ-lactone, which gave a α-monosubstituted δ-lactone upon heating in trifluoroacetic acid under reflux. Cyclopentanone can similarly be transformed into 2-substituted cyclohexanone via a three-step procedure.

A new method for the elimination of hydrogen halides and p-toluenesulfonic acid from sugar moieties using sodium hydride (NaH) in hexamethylphosphoric triamide (HMPA) at room temperature is reported. NaH/HMPA has several advantages compared to NaH/DMF: elimination products are produced in high yields even from sterically hindered starting materials, and not only from halides, but also tosylates.

Thymidine 4b was converted into 2,3′-anhydro-1-(2′-deoxy-β-D-threo-pentofuranosyl)thymine 7b in ∼65% isolated yield by being heated at 155 °C with an excess of diphenyl sulfite and 1-methylimidazole in N,N-dimethylacetamide solution. 2′-Deoxyuridine 4a, 2′-deoxy-5-ethyluridine 4c and 2′-deoxy-5-fluorouridine 4d were similarly converted into 2,3′-anhydronucleosides which were isolated as their 5′-O-(tert-butyldimethylsilyl) derivatives 8a, 8c and 8d in 51, 50 and 59% yield, respectively. When the oxetane derivatives 5a–d, prepared by the literature procedure from the parent 2′-deoxynucleosides 4a–d, were heated with an excess of sodium hydride in N,N-dimethylacetamide solution at 100 °C, they were converted into the corresponding 2′,3′-didehydro-2′,3′-dideoxynucleo-sides 6a–d in 68, 76, 69 and 74% isolated yield, respectively. The latter compounds were similarly prepared from the 2,3′-anhydronucleosides 7a–d in 71, 81, 69 and 74% isolated yield, respectively. 2,3′-Anhydro-5′-O-(tert-butyldimethylsilyl)-2′-deoxy-5-(trifluorornethyl)- and -5-iodo-1 -(β-D-threo-pentofuranosyl)uracil 8e and 8f, which were themselves prepared from the parent 2′-deoxynucleosides 4e and 4f, respectively, in ∼60 and 50% yield, were converted by a three-step procedure via the intermediate 2′-deoxy-3′-(phenylseleno) derivatives 10e and 10f into the corresponding 2′,3′-didehydro-2′,3′-dideoxynucleosides 6e and 6f in 52 and 49% overall yield, respectively. Compound 8e was also converted into 2′,3′-dideoxy-5-(trifluoromethyl)uridine 11b and 3′-azido-2′,3′-dideoxy-5-(trifluoromethyl)uridine 11c in 49 and 66% overall yield, respectively.

Poly(Nδ-4-nitrobenzoyl-L-ornithine) was obtained with average molecular weight 8.0 × 104 by reaction between the monomer N-carboxyanhydride and sodium hydride. The material was dipcoated onto platinum from dimethylacetamide solution and the behaviour of the coating examined in acetonitrile by cyclic voltammetry. Surface coverages in the range of 13.8 to 1.4 mmol cm–2 4-nitrobenzoyl residues were obtained by dipping from 0.6–0.07% solution, corresponding to from 20 to 2 layers of close-packed α-helices. The coated electrodes showed ipc proportional to scan rate. They do not show the severe ageing phenomena on repeated cyclic voltammetry that was associated with poly(NIµ-4-nitrobenzoyl-L-lysine). Expressions are developed which simulate the voltammograms by introducing activity coefficients for reduced and oxidised species within these multilayer films.

2λ4δ2-Thieno[3,4-c]thiophenes 1a, 1c and 1d possessing t-butylthio substituents reacted with trifluoroacetic acid to give the thione derivatives 3a, 3′c and 3′d through the intermediary formation of a proton adduct, 1H-thieno[3,4-c]thiophenium trifluoroacetates, followed by cleavage of the But–S bond. Treatment of the thione 3a with sodium hydride and then an alkyl iodide gave 2λ4δ2thieno[3,4-c]thiophenes 1c and 5–7. The reaction of 2λ4δ2-thieno[3,4-c]thiophenes 1a–e with trifluoroacetic acid and water resulted in the formation of thieno[3,4-c] thiophen-1(3H)-ones 9–12. Compounds 1a and 1b reacted with Vilsmeier reagent to give mono- and di-formyl-substituted 2λ4δ2-thieno[3,4-c]thiophenes 15a, 15b and 16b. Furthermore, formyl-substituted derivatives 15a and 16b reacted with malononitrile, ethyl cyanoacetate, and N,N-dimethylhydrazine to give the condensed compounds 17–21.

A substitution approach for the synthesis of 8-(mannosyloxy)adenosines, novel nucleoside–carbohydrate hybrids found in a new family of chitin synthase inhibitor—guanofosfocins, has been investigated. When an N6-benzoyl-8-bromoadenosine derivative was exposed to the sodium alkoxides derived from di-O-isopropylidene-D-mannoses or cyclohexanols, substitution occurred at room temperature to yield 8-(mannosyloxy)-adenosines and their 8-cyclohexyloxy derivatives. The 8-mannosyloxy products were isolated solely as α anomers and adopted a syn conformation with respect to the anomeric C–N bond. Whilst the hybrid compounds were obtainable in good yields, the new glycosidic linkage was acid sensitive to furnish 8-oxoderivatives under deprotecting conditions for the dimethoxytritylgroup. The synthesis of structurally unique nucleoside analogs is of considerable importance in the development of antiviral, antibiotic, antitumor and antifungal agents Naturally occurring compounds often provide inspiration for the creation of such analogs and a recently isolated family of chitin synthase inhibitor, guanofosfocins, stimulated our interest. The guanofosfocins, isolated from the fermentation broths of Streptomycessp. and Trichodermasp., have a unique cyclic structure containing a glycosidic bond between the 8-position of guanosine and a D-mannose moiety (Fig. 1) Despite their promising therapeutic effects against fungal diseases, further investigation of these fascinating molecules has been hindered by their low stability Since the ethereal bond between a glycosyl moiety and the 8-position of a purine nucleoside found in guanofosfocin is previously unknown, we planned to develop methodology for the efficient construction of this linkage in order to synthesise novel nucleoside–carbohydrate hybrids for screening and to evaluate their stability. One possible strategy for the synthesis of an 8-(glycosyloxy)purine nucleoside would be to substitute a protected carbohydrate-type nucleophile into a purine substrate bearing a leaving group at the 8-position. To date, simple 8-alkoxypurine nucleosides (8-methoxy and 8-benzyloxy substituted derivatives) have been prepared by such a method–6 However, the reaction conditions (e.g. non-protected nucleosides are treated with excess alcohol and sodium metal in DMSO at 65°C or higher) are unsuitable for sensitive carbohydrate-type nucleophiles. Therefore, prior to the introduction of a carbohydrate moiety, we endeavored to establish a general substitution procedure using an easily accessible purine nucleoside substrate, 8-bromoadenosine, and a simple secondary alcohol, cyclohexanol.As the substitution reaction conditions will be basic, the protecting groups employed on 8-bromoadenosine must be base stable. We first prepared a 2′,3′-O-isopropylidene-5′-O,N6-ditrityl substrate 1a, which was treated with sodium cyclohexyloxide generated insitu from cyclohexanol and sodium hydride in DMF.‡ Whilst no reaction occurred at room temperature, on heating the mixture at 70°C the reaction proceeded and, after 24 h, the starting nucleoside was almost consumed to provide 8-(cyclohexyloxy)adenosine derivative 2a in 65% yield along with a 22% yield of 8-oxoadenosine 4 (run 1 in Table 1). A similar tendency was observed in the reaction of N6 free substrate 1b (run 2). By contrast, the reaction of N6-benzoylated substrate 1c was completed at room temperature in 4 h to afford 8-cyclohexyloxy product 2c in 75% yield (run 3). It has been reported that an N2-acyl group on guanosine derivatives enhances the rate of intramolecular cyclization at the 8-position The benzoyl group at N6 of adenosine increases the rate of substitution by a similar electronic effect.The formation of 8-oxo byproduct 4 is due to hydrolysis of an addition intermediate 3 (Fig. 2) as attempts to form 4 directly by treating the substrates with sodium hydride alone in wet DMF were unsuccessful. Prolonged reaction, however, didn't lead to improvement in the yield of 2.Since selective deprotection at the 5′-position is required for further studies, other protecting groups at this position were briefly examined. 5′-O-tert-Butyldiphenylsilyl-protected substrate 1d underwent desilylation under the reaction conditions to yield 5′-hydroxyl product 2d (run 4). 5′-O-Dimethoxytrityl (DMTr) derivative 1e, in which the DMTr group can be removed more readily than the Tr group reacted with cyclohexanol to furnish the desired product 2e in good yield (run 5).Several other base–solvent combinations were also investigated (DMSO as an alternative solvent and ButOK/18-crown-6, Et3N as an alternative base), but sodium hydride in DMF gave the most satisfactory results.With a suitable substrate in hand, we turned our attention to the substitution reaction of carbohydrate-type nucleophiles (Table 2). When 2,3,4,6-tetra-O-benzylmannopyranose (5) was allowed to react with 1e, 8-(benzyloxy)adenosine 9 was isolated (run 1). From this result, it was deduced that base catalyzed ring opening of 5 was occurring and subsequent β-elimination of benzyloxide resulting in the formation of the 8-benzyloxy product. We anticipated that protection of the 2- and 3-hydroxy groups as a cyclic acetal would restrain this process, allowing the desired reaction to proceed. Indeed, when 2,3;4,6-di-O-isopropylidene-D-mannopyranose (6), prepared by a known route was used as a nucleophile, 8-(mannopyranosyloxy)adenosine derivative 11 was successfully obtained in good yield (run 2). Similarly, the corresponding 8-(mannofuranosyloxy)adenosine derivative 12 and the 8-(mannopyranosylthio)adenosine derivative 13 have been prepared using 2,3;5,6-di-O-isopropylidene-D-mannofuranose (7) and 2,3;4,6-di-O-isopropylidene-1-thio-D-mannopyranose (8), respectively (runs 3 and 4).The mannose–adenosine hybrids obtained here were formed as single isomers. Generally, the configuration of glycosidic linkages in pyranoses can be determined from 13C NMR spectra by measuring the 1JCH coupling at C-1 In hybrid 11, the coupling constant is 178 Hz, showing the new linkage to be exclusively α10,11 which is consistent with the mannosyl bond in guanofosfocins.In addition to the new carbohydrate–nucleoside hybrids, a substrate derived form myo-inositol was employed in the reaction to create a novel 8-inositol substituted adenosine compound 14 (run 5).Next, we briefly examined deprotection at the 5′-position. Dimethoxyltrityl group can be removed by trichloroacetic acid in nitromethane–methanol solvent system with little or no concomitant depurination However, when these conditions were applied to the nucleoside–carbohydrate hybrids 11–13, the glycosidic bond was cleaved to give the 8-oxo or 8-thioxo product 17 (runs 1–3 in Table 3). The 8-cyclohexyloxy derivatives 2e and 14 were acid stable, so that the dimethoxytrityl group could be removed without difficulty (runs 4 and 5). Efforts to investigate the selective deprotection conditions, not affecting the glycosidic bond, are currently underway.One intriguing feature of the guanofosfocins (Fig. 1) is that they clearly adopt an anti conformation about the anomeric C–N bond though purine nucleosides with bulky substituent at C-8 are known to have a syn conformation–15 It is well documented that the chemical shifts of H(2′) protons in syn and anti adenosines differ through changes in the torsion angle around the glycoside bond–15 It is therefore possible to predict the glycosyl conformation of the hybrids by comparing their shifts with compounds of known orientation. 8-Bromoadenosines are known to adopt syn conformations with the H(2′) signal characteristically located 0.5–0.6 ppm downfield from the H(3′) signal In this respect, hybrid compounds 11 and 12 show patterns similar to 1e, indicating a syn orientation. The 8-(cyclohexyloxy)adenosine 2e also shows a typical syn pattern. However, on removal of the bulky dimethoxytrityl group, the H(2′) signal of compound 15 shifted upfield to give a 1H NMR spectra consistent with an anti relationship. This finding is significantly important because an anti relationship is beneficial for future attempts to prepare guanofosfocin type compounds.In summary, by successfully forming the purine–carbohydrate bond found in guanofosfocin we have prepared a new type of nucleoside–carbohydrate hybrid. The approach will be compatible with the use of a variety of nucleophiles. The glycosidic linkage is extremely acid labile and this may contribute to the instability of the natural products. Further study on the application of this approach to the preparation of a wide variety of nucleoside hybrid molecules, including the use of guanosine substrates, is in progress. Acknowledgement

The title compound was synthesised by 1 : 1 reaction of sodium hydride with a di(aminoaryl) ether ligand in toluene–hexamethylphosphoramide (HMPA) solution; X-ray crystallography revealed that an in situ Smiles rearrangement of the ligand had taken place to give a dimeric aryloxide sodium complex, which is in stark contrast to previous results obtained by 2 : 1 reaction of BunLi with the ligand in the absence of HMPA.

An effective synthesis has been developed for 2,3′-biquinolyls using nucleophilic addition of sodium hydride to quinoline and its alkyl derivatives.

In this study, we exploit the alpha-acidity of saturated fatty acid methyl esters (FAMEs) for the direct conversion of these renewable raw materials to malonate derivatives. After deprotonation with sodium hydride in dimethyl carbonate (DMC) as reactive solvent, the ester enolates react with DMC to give the desired products with up to 80% isolated yield. These malonate derivatives, bearing a long aliphatic chain with chain lengths of C6–C16, were then polymerized to yield polyesters and polyamides. The polyesters were obtained by copolymerization with 1,6-hexanediol and titanium isopropoxide as a catalyst. For the polyamides, 1,6-hexanediamine was used with 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) as a catalyst. The obtained polyesters are highly viscous and tacky materials with low melting points and a molecular weight range of 9–17 kDa. The polyamides, on the other hand, are high melting polymers with molecular weights from 7–15 kDa.

Nucleophilic addition-elimination of ortho- or para-substituted phenols to aryl trifluorovinyl ethers (TFVEs) in N,N-dimethylformamide was studied. Using sodium hydride as a base afforded vinyl substitution products R-Ar-O-CF=CF-O-Ar-R', where R or R' = H, Br, OMe, tert-Bu, or Ph. The vinyl substitution products produced mixtures of (Z)/(E)-isomers and this isomer ratio was influenced by substitution with more sterically encumbered phenol nucleophiles. Reactions using caesium carbonate afforded addition products R-Ar-O-CHFCF(2)-O-Ar-R' whereas upon dehydrofluorination using sodium hydride produced vinyl substitution products. The preparation of vinyl substituted and addition products proceeded in overall good isolated yields and were elucidated using (1)H and (19)F NMR, GC-MS, and X-ray analysis. Vinyl substituted products were inert to UV light and chemical reactivity using common polymerization promoters. Thermal activation of the (Z)/(E)-fluoroolefin (-CF=CF-) was observed at an onset of 310 °C in nitrogen using differential scanning calorimetry (DSC) producing insoluble network material. The synthesis, characterization, and mechanism for stereoselectivity are discussed.

Tris(3,5-dialkyl-2-hydroxyphenyl)methanes (tert-butyl, tert-pentyl) react with three equivalents of sodium hydride to give hexanuclear dimers; these bulky aggregates have six well-defined coordination ‘pockets’ which demonstrate selectivity toward a variety of ketones.

Two series of monoaza-15-crown-5 compounds containing either a fused benzo group or sulfur donor atoms in the macrocycles have been synthesised by 1:1 cyclisation of diols or dithiols with ditosylates in the presence of sodium hydride; the molecular structure of 2,3-benzo-10-N-(4′-methoxyphenyl)-1,4,7,13-tetraoxa-10-azacyclopentadecane (8) has also been determined by single-crystal X-ray analysis.

The previously unreported title compound 4 is readily obtained by treating 2,2′-anhydro-1-β-D-arabinofuranosyl- uracil 1 with sodium hydride in dry dimethyl sulfoxide at room temperature.

Reaction of 1,3-dimethyl ether p-tert-butylcalix[4]arene (H 2 L) with sodium hydride in tetrahydrofuran affords the dimeric metallocalixarene species [Na 2 L] 2 which possesses a novel structure in which the Na + ions are coordinated in two very different environments.

4-Phenyl-3-oxobutanenitrile is synthesized via the reaction of ethyl phenylacetate with acetonitrile in the presence of sodium hydride and identified by isolating its 2-phenylhydrazone and dimethylaminomethylidene derivatives; both the hydrazone and dimethylaminomethylidene derivatives prove versatile starting materials for the synthesis of a variety of polyfunctionally substituted heterocycles.

Excellent Z or E selectivity is observed in the Horner–Wadsworth–Emmons reactions of methyl bis(trifluoroethyl)phosphonoacetate 2 with aryl alkyl ketones 3a–d or aldehydes 3f,g using Sn(OSO 2 CF 3 ) 2 in the presence of N-ethylpiperidine, which should have a different reaction mode to those using sodium hydride.

Sodium hydride selectively deintercalates the apex rather than face-shared oxide ions within the structure of Sr7Mn4O15 leading to the formation of the structurally related reduced phase Sr7Mn4O12.

Sodium hydride activates ruthenium carbene complexes to catalyze hydrogenation reactions subsequent to ring closing olefin metathesis. Under these conditions, hydrogenation of cyclopentenols proceeds smoothly at ambient temperature and under 1 atm of hydrogen in toluene. An alternative protocol was developed that involves the formation of hydrogen in situ by reaction of excess sodium hydride with protic functional groups and water.

The compound 2-PhOC6H4NHNa·NMe[(CH2)2NMe2]2has been synthesised by a 1 : 1 reaction of sodium hydride with 2-phenoxyaniline in toluene in the presence of N,N,N′,N″,N″-pentamethyldiethylene-triamine (pmdien); X-ray crystallography revealed a solid-state structure comprising a near-symmetrical Na2N2 ring dimer with each sodium cation chelated by a tridentate pmdien ligand in an unprecedented near-planar conformation.

An aza-Payne rearrangement of N-activated 2-aziridinemethanols, synthesized in an optically active form, with potassium tert-butoxide (ButOK), potassium hydride (KH), or sodium hydride (NaH) at near 0 °C in common aprotic solvents such as tetrahydrofuran (THF), toluene, or a mixed solvent of THF–HMPA followed by quenching at low temperature gives the corresponding epoxy sulfonamides in high yields. The anionic reaction intermediates, generated by treatment of 2-aziridinemethanols with a base, react readily in a one-pot manner with a variety of nucleophiles such as organocopper reagents, thiols, and trimethylsilyl cyanide to yield the optically active corresponding functionalized 1,2-amino alcohols in good yields. Upon exposure of 2,3-epoxy amines to an equimolar mixture of ButOK and BuLi (super base) in a mixed solvent of THF and n-hexane at –78 °C, the equilibrium lies exclusively toward the hydroxyaziridine forming direction.

Reaction of the tosyl imides 6 and 8 of 1,3-dithiane and 1,3,5-trithiane with sodium hydride and alkyl iodides in DMF yields anti alkylated products in all cases. In the case of the trithiane imide 8, both mono-and di-alkylation is observed. Preparation of cyclic sulfimide analogues of Eliel's oxathiane is shown to be problematic, but a new class of O,S-acetals, namely 4-bromophenylthiomethyl (BPTM) ethers, is introduced as a replacement for their troublesome phenylthiomethyl (PTM) analogues.

A new, direct synthesis is described for the relatively rare but synthetically very versatile quinazoline-2-carbonitriles from antranilonitriles and 4,5-dichloro-1,2,3-dithiazolium chloride 1. Treatment of iminodithiazole 6, from 4,5-dimethoxyanthranilonitrile and the salt 1, with alcohols and a base gives 4-alkoxyquinazoline-2-carbonitriles 8 in good yield. Treatment of the parent iminodithiazole 2 (R = H; X = CN) with alcohols and sodium hydride gives the analogous quinazolines 12 in lower yield, though these yields are much improved and the reaction times reduced under microwave irradiation. Alternatively the imine 6 can be converted into the more reactive cyanothioformamide 7 which on brief heating in alcohols gives the same quinazolines 8 in high yield.

Ring transformation of the adducts 1 of the polar cycloadditions of 2-benzothiopyrylium salts induced by a variety of bases and reducing agents has been investigated. Treatment of the 9-unsubstituted cycloadducts 1a, b, c with strong bases such as lithium diisopropylamide (LDA), sodium hydride and potassium carbonate afforded the vinylcyclopropane derivatives 2 and the 1,5-methano-2-benzothionines 3. In contrast, treatment of compound 1a with weak bases such as triethylamine, diethylamine and potassium acetate gave no compounds 2a or 3a, but only ring-opened compounds 4a in high yields via SN2-type processes. In these reactions, weak bases acted as nucleophiles. In contrast, the 9-benzoyl cycloadduct 1d reacted with both weak and strong bases to afford, mainly, the similar ring-transformed product 2d. Whilst the strong base LDA gave compound 3d(as a minor product) in addition to compound 2d, weak bases such as diethylamine and butylamine also acted as nucleophiles to give the corresponding ring-opened compounds 4d as minor products. A mechanistic interpretation of the above reactions is presented. When heated at high temperature, the vinylcyclopropane 2d was converted into the cyclopentene derivative 5. Ring transformations of compounds 1 with reducing agents such as sodium borohydride and samarium diiodide are also described.

Heating of dibromomethyl aryl ketones with tetrasulfur tetranitride (S4N4) at 115 °C without a solvent gave 3-aroylformamido-4-aryl-1,2-5-thiadiazoles 8 as major products (12–71%) and 3,5-diaroyl-1,2,4-thiadiazoles 2 as minor products in certain cases. The structures of compounds 8 were determined based on the X-ray analysis of 3-benzoylformamido-4-phenyl-1,2,5-thiadiazole 8a and comparison with an authentic sample of comound 8a, as well as all the spectroscopic and analytical data of compounds 8. Oxidation of compounds 8 with m-chloroperbenzoic acid in chloroform at room temperature gave compounds 2(0–66%), whereas reduction of compounds 8 with sodium boranuide in a mixture of chloroform–ethanol at room temperature gave 3-amino-4-aryl-1,2,5-thiadiazoles 10(71–93%). Treatment of 3-(3-nitrobenzoylformamido)-4-(3-nitrophenyl)-1,2,5-thiadiazole 8d with either sodium hydroxide in aqueous p-dioxane at reflux or sodium hydride in chloroform at room temperature gave 3-amino-4-(3-nitrophenyl)-1,2,5-thiadiazole 10d in 56 and 80% yield, respectively.

5-Benzylidene-2-phenyl-4,5-dihydro-1,3-oxazol-4-one was prepared by the cyclization of N-benzoyl-2-bromo-3-phenylpropenamide in the presence of sodium hydride.

1,1,2-Tribromocyclopropanes undergo 1,2-debromination with a dialkyl phosphite and either a trialkylamine or sodium hydride to form the corresponding 1-bromocyclopropene.

3-Amino-4-(2-nitroaryl)-2H-isoxazolin-5-ones, readily available by the sodium ethoxide catalysed cyclisation of amidoximes derived from ethyl 2-cyano-2-(2-nitroaryl)acetates, ring-close in the presence of sodium hydride to afford high yields of isoxazolo[3,4-c]cinnolin-1(3H)-one 5-N-oxides; hydrazine effects the chemoselective reductive scission of the isoxazoline ring in these heterocycles allowing simple and efficient synthetic access to erstwhile unavailable 3-aminocinnoline-4-carboxylic acid 1-N-oxides.

Thermal reaction of 1-cyano-2-methyl-3,4-dihydro-1H-2-thionianaphthaalen-1-ides 1 in ethanol afforded the spiro compounds 3 in good yields, which underwent thermal rearrangement and Diels–Alder reaction to give tetrahydro-3-benzothiepine 4 and a pair of cycloadducts 6 and 7, respectively. Treatment of 1 with succinimide similarly provided 3via the processes of protonation, ylide formation and [2,3]sigmatropic rearrangement. In contrast, treatment of 1a with N-chlorosuccinimide, chloramine B or T formed the chloroketenimine 16via an S→N [2,3]sigmatropic rearrangement of the exo-methanide 15. The exo-ylide 19 generated by deprotonation of the sulfonium salt 18 with sodium hydride underwent a similar [2,3] rearrangement to give the ketenimine 20. Hydrolysis of the ketenimines 16 and 20 with dilute hydrochloric acid produced amides 17 and 21, respectively. Reactions of 1 with dimethyl acetylenedicarboxylate proceeded via Michael addition followed by two different routes of ring-expansion to give the nine-membered cyclic sulfides 30 and the eight-membered cyclic sulfur ylides 32.

Nitrile oxide cycloadditions to readily available allylic diphenylphosphine oxides 2 proceeded regioselectively and stereoselectively to give 5-(1′-diphenylphosphinoylalkyl)isoxazolines 4 and 5. These heterocycles were reduced to δ-amino-β-hydroxyalkyldiphenylphosphine oxides 6 and 7 using a combination of sodium borohydride and nickel(II) chloride. Stereospecific elimination of diphenylphosphinic acid from the reduction products using sodium hydride in N,N-dimethylformamide gave homoallylic primary amines 8 and 9 of defined stereochemistry.

Two general routes are described for the synthesis of the title compounds from the reaction of either (A) the dimethyl acetal of N,N-dimethylformamide and an appropriate N,N′-bis(secondary amine), or (B) sodium hydride and a 4,5-dihydroimidazolium or tetrahydropyrimidinium salt. The following new compounds have been made: trans-R[graphic omitted][graphic omitted]R [R = Et and R′= Me (1a) or CH2Ph (1b)] and R[graphic omitted][graphic omitted]R [n=m= 2 and R= Me (2a) or CH2Ph (2b); n= 3, m= 2, and R= CH2Ph (3); or n= 2, m= 3, and R= CH2Ph (4)].X-Ray data on crystalline [graphic omitted]R]2(R = CH2Ph) and (2b)[data in parentheses] show a short CC bond, 1.319(8)A[1.329(5)A], long Csp2–N bonds, av. 1.437(11)A[1.424(4)A], with each of the four nitrogen atoms in a pyramidal sp3 environment.

Reaction of sodium hydride in thf (tetrahydrofuran) with H2salphen [N,N′-o-phenylenebis-(salicylideneimine)] or H2salen [N,N′-ethylenebis(salicylideneimine)] gave the corresponding sodium derivatives Na2(salphen)(thf)n and Na2(salen)(thf)n. Recrystallization from 1,2-dimethoxyethane (dme) gave the stable solvated forms [Na4(salphen)2(dme)2]2 and [Na4(salen)2(dme)2]2. From the X-ray analysis both have very similar structures with a cubane skeleton of alternate sodium and oxygen atoms. Crystallographic details: complex 1, space group P21/c, a= 12.045(1), b= 25.851(2), c= 16.467(1)Aα=γ= 90°, β= 107.61(1)°, Z= 4 and R= 0.079 for 2118 independent observed reflections; 2, space group P21/n, a= 20.493(2), b= 21.682(2), c= 20.538(2)A, α= 90°, β= 110.53(1)°, Z= 8 and R= 0.071 for 5054 independent observed reflections.