偶氮二甲酸二异丙酯的合成

以氯甲酸异丙酯、水合肼为主要原料,制备肼-1,2-二甲酸二异丙酯,然后用双氧水氧化制得偶氮二甲酸二异丙酯(DIAD)。 研究确定了最佳的反应条件:在0 ℃以下乙醚溶剂中,水合肼和氯甲酸异丙酯反应2 h,制备肼-1,2-二甲酸二异丙酯;n(肼-1,2-二甲酸二异丙酯)∶n(双氧水)=1:1.1,在-5~5 ℃下反应2 h,双氧水氧化得到偶氮二甲酸二异丙酯,总收率为90.7%,采用红外光谱、核磁共振等技术手段验证了中间体及目标产物结构。     

Di-p-nitrobenzyl azodicarboxylate (DNAD): an alternative azo-reagent for the Mitsunobu reaction

Di-p-nitrobenzyl azodicarboxylate is prepared in 83.6% yield in two steps as a bright yellow solid, which can be used as an azo-reagent in the Mitsunobu reaction. When a chiral secondary alcohol was used, sufficient configurational inversion of alcohol occurred under Mitsunobu conditions. That the hydrazine produced from DNAD is semisoluble in some solvents such as THF and CH₂Cl₂ makes it separated easily from the reaction mixture just via filtration. Then the recovered hydrazine compound can be re-exposed to oxidant to produce DNAD. Because DNAD is more stable than DIAD at ambient temperatures and allows easy separation, it is a good alternative azo-reagent for the Mitsunobu reaction.     

Simplification of the Mitsunobu reaction. Di-p-chlorobenzyl azodicarboxylate: a new azodicarboxylate

Di-p-chlorobenzyl azodicarboxylate (DCAD) is introduced as a novel, stable, solid alternative to DEAD and DIAD for a variety of Mitsunobu couplings. DCAD/Ph(3)P-mediated reactions in CH(2)Cl(2) generate a readily separable hydrazine byproduct. [reaction: see text]     

Improved conditions for converting sterically hindered amides to 1,5-disubstituted tetrazoles

Improved conditions for converting amides into 1,5-disubstituted tetrazoles are described. The optimum reaction conditions [diisopropyl azodicarboxylate (DIAD), diphenylphosphoryl azide (DPPA), and diphenyl-2-pyridyl phosphine in THF at 45 °C] converted sterically hindered amides to their corresponding tetrazoles in good yield.     

2‐Arylation/alkylation of benzothiazoles using superparamagneticgraphene oxide‐Fe3O4 hybrid material as a heterogeneous catalystwith diisopropyl azodicarboxylate (DIAD) as an oxidant

In this report, we introduced Graphene oxide‐iron oxide (GO‐Fe₃O₄) nanocomposites as a heterogeneous catalyst for arylation/alkylation of benzothiazoles with aldehydes and benzylic alcohols in the presence of diisopropyl azodicarboxylate (DIAD) as an oxidant which exclusively produced 2‐aryl (alkyl)‐1H–benzothizoles in moderate to excellent yields. The absence of precious metals and toxic solvent, easy product isolation, and recyclability of the GO‐Fe₃O₄ with no loss of activity are notable advantages of this method.     

Solid-phase synthesis of amine-bridged cyclic enkephalin analogues via on-resin cyclization utilizing the Fukuyama-Mitsunobu reaction

An efficient solid-phase synthetic route is described for the preparation of 13-membered amine-bridged cyclic enkephalin analogues (ABEs) 1a and 1c-1j (Figure 1) resulting from a sulfonamide-containing peptide whose backbone is bound to a resin. The Fukuyama-Mitsunobu reaction of the 2-nitrobenzenesulfonyl-protected amine bound to the solid support with protected aminoethanol in the presence of triphenylphosphine and diisopropyl azodicarboxylate (DIAD) is utilized to prepare a resin-bound sulfonamide-protected secondary amine. After peptide cyclization, this protected amine functionality becomes the "amine bridge" of the target molecule. In addition, the reagent DIAD was found to be a superior reagent compared to diethyl azodicarboxylate (DEAD) in the solid-phase Fukuyama-Mitsunobu reaction.     

NEW PROTOCOL FOR CONVERTING ALCOHOLS INTO AMINES

The reactions between diethyl N-(t-butoxycarbonyl)phosphoramidate 1, diisopropyl azodicarboxylate (DIAD), triphenylphosphine (TPP) and primary or secondary alcohols lead to the corresponding diethyl N-alkyl-N-(t-butoxycarbonyl) phosphoramidates 2a-o. Deprotection of crude 2 by refluxing with p-toluenesulfonic acid monohydrate in ethanol affords ammonium tosylates 3a-o in moderate to good overall yields. The N-alkylation of 1 proceeds stereoselectively with complete inversion of the configuration of the alkyl group.     

Oxidation of alcohols to carbonyl compounds with diisopropyl azodicarboxylate catalyzed by nitroxyl radicals

A nitroxyl-radical-catalyzed oxidation of alcohols using diisopropyl azodicarboxylate (DIAD) as the terminal oxidant is reported. A variety of primary and secondary alcohols including aliphatic, benzylic, and allylic alcohols are efficiently oxidized to their corresponding aldehydes and ketones without overoxidation to carboxylic acid. 1,2-Diols are oxidized to hydroxyl ketones or diketones depending on the amount of DIAD used.     

Elimination of beta-thioalkoxy alcohols under Mitsunobu conditions. A new synthesis of conjugated enynes from propargylic dithioacetals

Treatment of propargylic dithiolanes 1 with (n)BuLi followed by a carbonyl electrophile yields the corresponding homopropargylic alcohol 3. Upon treatment with 2 equiv of PPh3 and DIAD, elimination of SR and OH moieties from 3 affords the corresponding olefins 4 in moderate to good yield. The reaction can be considered an alternative of McMurry coupling of two different carbonyl equivalents.     

An improved Larock synthesis of quinolines via a Heck reaction of 2-bromoanilines and allylic alcohols

A modified Larock method has been developed for the one-pot synthesis of substituted quinolines via a Heck reaction of 2-bromoanilines and allylic alcohols followed by dehydrogenation with diisopropyl azodicarboxylate (DIAD).     

Synthesis of new diheteroarylcarbazoles: a facile and simple route of 3,6-di(pyrazol-4-yl)carbazoles

A short and facile route to the synthesis of new 3,6-di(pyrazol-4-yl)carbazoles is reported. Dipyrazolylcarbazoles were synthesized in two steps from 3,6-diacetylcarbazoles through a Vilsmeier reaction which led to the formation of carbazolyl-β-chlorovinyl aldehydes, followed by cyclization with hydrazine hydrate. The reaction of the Vilsmeier reagent with hydrazones of diacetylcarbazoles yielded the corresponding pyrazole dicarbaldehydes in good yields.     

Metal-free oxyaminations of alkenes using hydroxamic acids

A radical-mediated approach to metal-free alkene oxyamination is described. This method capitalizes on the unique reactivity of the amidoxyl radical in alkene additions to furnish a general difunctionalization using simple diisopropyl azodicarboxylate (DIAD) as a radical trap. This protocol capitalizes on the intramolecular nature of the process, providing single regioisomers in all cases. Difunctionalizations of cyclic alkenes provide trans oxyamination products inaccessible using current methods with high levels of stereoselectivity, complementing cis-selective oxyamination processes.     

Synthesis of amino terminated semifluorinated long-chain alkanethiols

The α,ω-diiodoperfluorooctane is added to undecyl-10-en-1-ol through AIBN initiation yielding the monoadduct in good yield (1,2-dichloroethane, 52%). This is added to N-allylphthalimide (AIBN initiation, 1,2-dichloroethane, 81%). The resulting diiodo compound is hydrodeiodinated with Bu₃SnH (toluene, 70%) and the alcohol function is converted to thioacetate through the Mitsunobu reaction (PPh₃, DIAD, THF, 75%). The two protecting groups, phthalimide and thioacetate, are removed with hydrazine to give the expected amino terminated semifluorinated long-chain alkanethiol (ethanol, 80%). This compound has been designed in order to form mixed fluorinated self-assembled monolayers (SAMs) with semifluorinated long-chain alkanethiol giving access to a new platform system for biosensors. Similar results are reported starting from the α,ω-diiodoperfluorohexane.     

[4+2] Cycloaddition Reactions Between 1,8‐Disubstituted Cyclooctatetraenes and Diazo Dienophiles: Stereoelectronic Effects,Anticancer Properties and Application to the Synthesis of 7,8‐Substituted Bicyclo[4.2.0]octa‐2,4‐dienes

A detailed examination of [4+2] cycloaddition reactions between 1,8‐disubstituted cyclooctatetraenes and diazo compounds revealed that 4‐phenyl‐1,2,4‐triazole‐3,5‐dione (PTAD) reacts to form either 2,3‐ or 3,4‐disubstituted adducts. The product distribution can be controlled by modulating the electron density of the cyclooctatetraene. Unprecedented [4+2] cycloadditions between diisopropyl azodicarboxylate (DIAD) and 1,8‐disubstituted cyclooctatetraenes are also described and further manipulation of a resulting cycloadduct uncovered a new pathway to the synthetically challenging bicyclo[4.2.0]octa‐2,4‐diene family. Variation of the substituents resulted in a range of compounds displaying selective action against different human tumour cell types.     

Pentacoordinate phosphoranes with reversed apicophilicity as stable intermediates in a mitsunobu-type reaction

Diisopropyl azodicarboxylate (DIAD) undergoes a cycloaddition reaction with the cyclic phosphites CH(2)(6-t-Bu-4-Me-C(6)H(2)O)(2)PX (1) [X = NCS (a), N(3) (b), Cl (c), NHMe (d) and Ph (e)] to afford the novel pentacoordinate phosphoranes 2a-e as crystalline solids. This result is different from the reaction of PPh(3) with DIAD used in the well-known Mitsunobu reaction. X-ray crystallography of 2a, 2b, and 2d reveals that the nitrogen, rather than the oxygen, occupies an apical position of the trigonal bipyramidal phosphorus. This is in violation of the commonly accepted preferences for substituents in trigonal bipyramidal phosphorus. In 2e, although the oxygen of the five-membered ring occupies the expected apical position, the phenyl group also occupies (the other) apical position, forcing the more electronegative oxygen atoms of the eight-membered ring to span equatorial-equatorial positions. In contrast to the above, the isocyanato compound CH(2)(6-t-Bu-4-Me-C(6)H(2)O)(2)PNCO (1f), upon treatment with DIAD, affords compound 3 to which a tetracoordinate structure is assigned.     

Selective Synthesis in Microdroplets of 2-Phenyl-2,3-dihydrophthalazine-1,4-dione from Phenyl Hydrazine with Phthalic Anhydride or Phthalic Acid

Pyridazine derivatives are privileged structures because of their potential biological and optical properties. Traditional synthetic methods usually require acid or base as a catalyst under reflux conditions with reaction times ranging from hours to a few days or require microwave assistance to induce the reaction. Herein, this work presents the accelerated synthesis of a pyridazine derivative, 2-phenyl-2,3-dihydrophthalazine-1,4-dione (PDHP), in electrosprayed microdroplets containing an equimolar mixture of phenyl hydrazine and phthalic anhydride or phthalic acid. This reaction occurred on the submillisecond timescale with good yield (over 90 % with the choice of solvent) without using an external catalyst at room temperature. In sharp contrast to the bulk reaction of obtaining a mixture of two products, the reaction in confined microdroplets yields only the important six-membered heterocyclic product PDHP. Results indicated that surface reactions in microdroplets with low pH values cause selectivity, acceleration, and high yields.     

A versatile method for the synthesis of substituted 1-aminohydantoin derivatives

An efficient and versatile method has been developed for the synthesis of 1-aminohydantoin derivatives which can be substituted at all the possible positions of the hydantoin ring. The starting materials are aldehydes, ketones, carboxylic acids and hydrazides as well as isocyanates readily available from commercial sources. The semicarbazide-type reaction product of an N-acyl-N′-(1-cyanoalkyl)hydrazine, obtained from the above materials by methods known from the literature, and an isocyanate is cyclized in the presence of a basic catalyst to yield 1-acylamino-4-imino-2-oxoimidazolidine derivatives whose acid catalyzed hydrolysis leads to 1-aminohydantoin derivatives in good to excellent yields. The last two steps are carried out in a single reaction medium.     

An Improved Synthesis of Ethyl Azodicarboxylate and 1,2,4-Triazoline-3,5-Diones Using Hypervalent Iodine Oxidation

ARSTRACT: Hypervalent iodine oxidstion of 1,2-dicarhethoxy hydrazine (1) and 4-substituted urazoles (3) using iodobenzene diacetate or pentafluoroiodobenzene bis-trifluoroacetate in CH₂Cl₂ at room temperature proceeds smoothly to yield ethyl azodicarboxylate (2) and 4-substituted 1,2,4-triazoline-3,5-diones (4) in excellent yields.     

Synthesis,NMR, and X-ray crystallographic analysis of C-hydrazino-C-carboxycarboranes: versatile ligands for the preparation of BNCT and BNCS agents and (99m)Tc radiopharmaceuticals

Protected hydrazine derivatives of ortho-, meta-, and para-carboranes were synthesized in good to excellent yields by reacting the mono-lithio salts of the respective carboranes with di-tert-butyl azodicarboxylate (DBAD). Subsequent deprotonation of the remaining carborane CH group, followed by the addition of CO(2)(g), resulted in the formation of bifunctional C-hydrazino-C-carboxycarboranes in good to excellent overall yields. Crystal structures of the monosubstituted ortho-carborane, 1-[(N,N'((tert-butyloxy)carbonyl)hydrazino)]-1,2-dicarba-closo-dodecaborane (8) [a = 21.213(6) A, b = 10.498(3) A, c = 9.866(2) A, alpha = gamma = 90 degrees, beta = 90.529(4) degrees ] and the bifunctional para-carborane 1-[(N,N'((tert-butyloxy)carbonyl)hydrazino)]-1,12-dicarba-closo-dodecaborane-12-carboxylic acid (3) [a = 12.744(10) A, b = 12.875(9) A, c = 14.767(9) A, alpha = beta = gamma = 90 degrees ] were obtained. Intermolecular hydrogen bonding was a dominant packing feature in both structures. The reported compounds represent a unique class of bifunctional carboranes that can be used in peptidomimetic research and as synthons to prepare novel radiopharmaceuticals and boron neutron capture therapy/boron neutron capture synovectomy (BNCT/BNCS) agents.     

Cycloadditions of anionic N-heterocyclic carbenes of sydnone imines

Sydnone imines were deprotonated with lithium bis(trimethylsilyl)amide at the C4 position to give the corresponding sydnone imine anions as lithium adducts. These can be represented as lithium stabilized anionic N-heterocyclic carbenes. Treatment with diisopropyl azodicarboxylate (DIAD) gave the corresponding C4 adducts, i.e. 4-hydrazinyl-sydnone imines, which form tautomers in solution. Reductive 1,3-dipolar cycloadditions of the sydnone imine anions with tetracyanoethylene (TCNE) resulted in the formation of pyrazoles, the mechanism of formation of which differs from known reactions. Reaction of the anion derived from the 2-methoxyphenyl sydnone imine with N,N-diisopropylcarbodiimide gave a ring-cleaved bisiminonitrile. Structure elucidations were accomplished by NMR spectroscopy and by four single crystal X-ray analyses.