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Ultrasonography (US) is a noninvasive and patient-friendly tool for the evaluation of peripheral nerves. In motor neuron diseases, amyotrophic lateral sclerosis (ALS) has been reported to show the atrophy of peripheral nerves on US. However, the US findings are still unclear in spinal and bulbar muscular atrophy (SBMA), an adult-onset lower motor neuron disease caused by an abnormal CAG repeat expansion in the androgen receptor gene.We prospectively recruited and evaluated 11 patients with genetically confirmed SBMA and 9 patients with ALS diagnosed according to the revised El Escorial ALS criteria or the Awaji electrodiagnostic criteria. The C5-C7 cervical nerve roots and the median and ulnar nerves were evaluated ultrasonographically.The cross-sectional areas (CSAs) of the C6 and C7 nerve roots, the median nerve in the upper arm and forearm, and the ulnar nerve in the upper arm were smaller in patients with SBMA than those in patients with ALS (p 0.05), whereas the CSAs of the C5 nerve root and the ulnar nerve in the forearm were not smaller.US showed that the peripheral nerves in patients with SBMA were thinner than those in patients with ALS despite similar degrees of weakness and motor neuron loss. Possible causes include additional sensory nerve involvement and longer disease duration in patients with SBMA than those in patients with ALS.

Herein, we describe the guanidine-promoted synthesis of carbonates from glycerol, CO2, and alkyl halides. Specifically, a linear tricarbonate (1,2,3-tri-O-butoxycarbonylglycerol), a dicarbonate [butyl (2-oxo-1,3-dioxolan-4-yl)methyl carbonate] containing a linear and a cyclic moiety, and a cyclic monocarbonate (4-hydroxymethyl-2-oxo-1,3-dioxolan) were selectively obtained in good yields, which were strongly affected by the steric bulkiness of the guanidine group substituents. The developed method exhibits the advantages of high efficiency and mild conditions, thus being a powerful tool for the synthesis of value-added products from industrial by-products.

The arylation of aromatic diamines with arylhydrazine hydrochlorides was achieved in reasonable yields. This new and simple reaction occurred at room temperature in air using an inexpensive base. This transformation seems to proceed via a homolytic aromatic substitution (HAS) mechanism. The synthesized aromatic diamines are used as raw materials for polyimides, including important aerospace materials, for example, Kapton®.

Cyclic phosphorus compounds, 6H-dibenz[c,e][1,2]oxaphosphorin-6-oxide derivatives, were efficiently synthesized by the Friedel–Crafts reaction of 2-hydroxybiphenyls with phosphorus trichloride in the presence of superacids, especially trifluoromethanesulfonic acid (TfOH) as a catalyst. TfOH was investigated for the first time as an effective catalyst for the aromatic phosphination of 2-hydroxybiphenyls.

A direct C–H arylation of aminoheterocycles with arylhydrazine hydrochlorides was developed. The reaction proceeds via a homolytic aromatic substitution mechanism involving aryl radicals as the intermediates. The new reaction takes place readily at room temperature in air and in the presence of an inexpensive base. Moreover, the reactivity of this radical arylation correlated with the HOMO energy of aminoheterocycles. This method provides not only a rapid access to diverse arylated heterocycles, but also an atom-efficient alternative to conventional transition-metal-catalyzed cross-coupling between halides and organometallics.

A new method for the hydrolysis of diazonium salts, without the formation of tar, was developed. A two-phase system consisting of cyclopentyl methyl ether (CPME) and water is very effective for the hydrolysis of diazonium salts. Using this solvent system, the diazonium salt prepared from 3-(4-nitrophenoxy)aniline gave 3-(4-nitrophenoxy)phenol in high yield (96%) within 20 min. The synthesized phenol is an industrially important raw material in polymer syntheses. Furthermore, the use of the present two-phase system of CPME and water successfully brought about the efficient conversions of several m-substituted anilines into the corresponding m-substituted phenols. This is the first example of hydrolysis of diazonium salts using the two-phase system (CPME and water).

A novel synthesis of unsymmetrical aryl sulfides, which requires no transition metal catalyst and no oxidant, was developed. This base-promoted cross-coupling reaction proceeded using arylhydrazines and 1 equiv amount of disulfides under inert gas conditions to afford the unsymmetrical aryl sulfides in good yields.

A catalyst based on iron and elemental sulfur has been shown to efficiently promote a redox-neutral reaction between 2-nitrophenols and 2,6-disubstituted p-cresols, allowing for the preparation of 2-arylbenzoxazoles in good yields. This synthetic methodology also affords high atom economy without the use of any external oxidizing and/or reducing reagents. This is the first redox–condensation reaction of 2-nitrophenols with 2,6-disubstituted p-cresols.

A direct C–H arylation of aminoheterocycles with arylhydrazine hydrochlorides was developed. The reaction proceeds via a homolytic aromatic substitution mechanism involving aryl radicals as the intermediates. The new reaction takes place readily at room temperature in air and in the presence of an inexpensive base. Moreover, the reactivity of this radical arylation correlated with the HOMO energy of aminoheterocycles. This method provides not only a rapid access to diverse arylated heterocycles, but also an atom-efficient alternative to conventional transition-metal-catalyzed cross-coupling between halides and organometallics.

The bicyclic amidines, 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU) and 1,5-diazabicyclo[4.3.0] non-5-ene (DBN), were used for the chemical fixation of carbon dioxide. The promotion for CO2 fixation is often reported through the formation of a thermally unstable DBU or DBN bicarbonate salt. To examine the effects of the DBU or DBN bicarbonate salt, reactions of 2-aminobenzonitrile with the DBU salt or DBN salt in dimethylformamide (DMF) were performed at 20°C for 24 h in argon or carbon dioxide (0.1 MPa). However, in all the cases, 1H-quinazoline-2,4-dione was not obtained completely. In contrast with room temperature reactions, 2-aminobenzonitriles and DBU bicarbonate salt in DMF reacted for 4 h under high temperature (80°C) and CO2 atmosphere (0.1 MPa) gave 1H-quinazoline-2,4-diones in good to excellent yields. At high-temperature conditions, DBU bicarbonate salt is decomposed to DBU and carbon dioxide. Also, the carbonylation of 2-aminobenzonitrile using DBU and carbon dioxide afforded 1H-quinazoline-2,4-dione in good yields under similar reaction conditions. These results suggest that the combination of DBU or DBN as a strong base and carbon dioxide is much more important than the in situ formation of DBU or DBN bicarbonate salt for the acceleration of CO2 fixation. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 23:276–280, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.21014

4,6-Diaminoresorcinol, which is a raw material of ZYLON (PBO fiber), has an instability in air atmosphere. Therefore, very stable benzo[1,2-d:5,4-d']bis-2(3H)-oxazolone recognized a useful equivalent of 4,6-diaminoresorcinol during the stages of production, storage, and transportation. By combining the sulfur-assisted carbonylation of 4,6-diaminoresorcinol dihydrochloride with carbon monoxide and triethylamine under 0.1 MPa at 20°C for 4 h in DMF with the oxidation of resulting hydrogen sulfide salt with molecular oxygen for 2 h, benzo-[1,2-d:5,4-d']bis-2(3H)-oxazolone was obtained in a quantitative yield. Also, carbonylation of 2,5-diaminohydroquinone dihydrochloride and 2,5-diamino-1,4-benzenedithiol dihydrochloride was smoothly performed to give benzo[1,2-d:4,5-d']bis-2(3H)-oxazolone and benzo[1,2-d:4,5-d']bis-2(3H)- thiazolone, respectively, in good to excellent yields under similar reaction conditions. Furthermore, 2,6-dimercaptobenzo[1,2-d:5,4-d']bisoxazole, which is another equivalent of 4,6-diaminoresorcinol, was obtained in excellent yield by the thiocarbonylation of 4,6-diaminoresorcinol dihydro-chloride with carbon disulfide in the presence of 1-methylpyrrolidine at 20°C for 24 h in DMF. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 23:111–116, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20746

Polystyrene latexes prepared using a carbon dioxide switchable amidine surfactant and a switchable free radical initiator can be aggregated using only nitrogen and gentle heat and redispersed using carbon dioxide and sonication. The long-term colloidal stability of the redispersed latexes is excellent provided they are maintained under a carbon dioxide atmosphere. Redispersion of the particles is most effective when both the surfactant and the initiator contain switchable amidine moieties. The zeta potential of the original particles (with the switchable surfactant/initiator in their active form) decreases when the surfactant and initiator are converted to their inactive form upon addition of nitrogen and heat. Zeta potential is restored to its original value upon conversion of the surfactant and initiator to their active forms with carbon dioxide addition. This is the first report of redispersible polymer colloids that can be aggregated by reduction of surface charge, without requiring added acid or base...

In the presence of a catalytic amount of selenium under ambientpressure of carbon monoxide with oxygen, solvent-free facile synthesisof urea derivatives was developed; the aim is for green and sustainablechemistry. For example, N, N′-dimethylethylenediamine (20mmol) successfully afforded 1,3-dimethylimidazolidin-2-one (DMI)in 74% yield (1487% based on Se) using seleniumcatalyst (5 mol%) under mixed gas (CO/O 2 ,2:1) at 0.1 MPa, 20 ˚C without any additive or solvent.

With ambient pressure of carbon monoxide and oxygen at room temperature, N,N-dialkyl-N'-arylureas were selectively accessible from secondary amines, aromatic amines, and sulfur in good to excellent yields. For example, N-butyl-N-methyl-N'-(3,4-dichlorophenyl)urea, which is used as a herbicide (neburon), was afforded successfully from butylmethylamine (2 equiv), 3,4-dichloroaniline (1 equiv) and sulfur (1 equiv) in 79% (21.8 g) yield using carbon monoxide (0.1 MPa) and oxygen (0.1 MPa) at 20 °C in DMF.

The efficient cross-coupling reaction to afford ketones from pyridine carboxylic acid chlorides and alkylzinc reagents in the presence of Pd(phen)Cl 2 is reported. In the case of chloronicotinoyl chlorides, none ofNegishi cross-coupling products of 2-chloroazine moiety was formed. The catalyst loading could be reduced up to 0.01 mol%.

The first example of cyclic urea synthesis from secondary amines by the use of sulfur-assisted carbonylation and oxidation was established. By combined sulfur-assisted carbonylation of secondary α,ω-diamines under an ambient pressure of carbon monoxide at 20°C with oxidation by molecular oxygen (0.1 MPa, 20°C), a facile synthetic method for N,N′-dialkyl cyclic ureas including 1,3-dimethyl-2-imidazolidinone was developed. © 2009 Wiley Periodicals, Inc. Heteroatom Chem 20:64–68, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20508

A solvent-free carbonylation and oxidation system aimed at green and sustainable chemistry was developed. With these reactions, an environmentally benign synthesis of urea derivatives could be carried out in good to excellent yields from primary amines and sulfur at ambient pressure of carbon monoxide and oxy-gen. For example, N, N′-dioctylurea was prepared in 99% yield from two equivalents octylamine and one equivalent sulfur in the presence of carbon monoxide (1 atm) at 80 °C and oxygen (1 atm) at room temperature, in the complete absence of solvent.

A new and facile synthetic method for urea derivatives was developed under mild conditions, and contrasts with conventional preparation methods that need highly toxic reagents (phosgene) or severe reaction conditions. In our reaction system, N,N-dimethylformamide or dimethyl sulfoxide as solvent strongly accelerated the carbonylation of primary amines with sulfur under carbon monoxide (1 atm) at 20 °C to give the corresponding thiocarbamate salts. These salts were readily oxidized by molecular oxygen under similarly mild conditions to afford urea derivatives in good to excellent yields. This urea synthesis could also be applied to a new synthesis of aromatic ureas by use of 1,8-diazabicyclo[5.4.0]undec-7-ene in N,N-dimethylformamide.

A novel and efficient synthesis of 3,4,5-triaryltetrahydro-1,4-thiazine derivatives by treatment of β,β′-dichloro sulfides, 2:1 adducts of alkenes and sulfur dichloride, with aromatic amines in the presence of silica gel is described. The silica gel can be easily recovered and reused in up to four consecutive reactions without any significant decrease in product yield.

Treatment of a mixture of alkyl aldehydes (1) with acid chlorides (2) in the presence of zinc metal powder and a catalytic amount of chlorotrimethylsilane (TMSCl) in dichloromethane brought about highly facile and effective coupling to give selectively the corresponding α-haloacylation and gem-bisacylation products, α-haloalkyl carboxylates and 1,1-dicarboxylates (acylals), in good to excellent yields.

Treatment of acid chlorides (2) with allyl chlorides (1) in the presence of zinc dust and a catalytic amount of chlorotrimethylsilane (TMSCl) in THF brought about highly facile and effective coupling to give the corresponding gem-bisallylation products, 4-hydroxy-penta-1,6-dienes (3), in good to excellent yields. These reactions are assumed to proceed through allylzinc intermediates generated in situ.

Substitution of 2,6-di-tert-butyl-p-cresol (II) by 2-tert-butyl-p-cresol, 2,6-dimethoxy-p-cresol or 1-tert-butyl-toluene results in the isolation of the corresponding products in small or trace amounts only.

Progressive external ophthalmoplegia (PEO) is one of a number of major types of mitochondrial disorders. Most sporadic PEO patients have a heteroplasmic large deletion of mitochondrial DNA (mtDNA) in the mitochondria in skeletal muscles. We herein analyzed mtDNA deletions using sub-cloning and Sanger sequencing of PCR products in a 31-year-old Japanese man with multiple symptoms, including PEO, muscle weakness, hearing loss, leukoencephalopathy and hypogonadism. A large number of multiple deletions was detected, as well as four kinds of deletion breakpoints identified in different locations, including m.3347_12322, m.5818_13964, m.5829_13964 and m.5837_13503.

Efficient oxidation system using reusable vanadyl(IV) sulfate catalyst was established. Toluenes were easily oxidized under molecular oxygen (0.1 MPa) at 100 °C catalyzed by vanadyl(IV) sulfate to afford the corresponding benzoic acids in excellent yields. The recovered catalyst could be reused without loss of activity.

An efficient, eco-friendly, and mild method for the acylation of various nucleophiles with acid anhydrides using iron(III) chloride is described. The addition of only 0.1―2 mol% of iron chloride catalyzed the acylation under solvent-free conditions at room temperature to give the acylated products in good yields.

A reduction of organic solvents in the organic chemical industry is of serious importance for sustainable chemistry. With this viewpoint, we successfully established the useful dehydrogenation of hydrazo compounds using basic alumina or KF/alumina -under solvent-free conditions to afford azo compounds in good to excellent yields.

A combination of zinc metal and a catalytic amount of chlorotrimethylsilane has been found to promote the transformation of various aldehydes and ketones with gem-dichloro compounds, such as benzylidene dichloride (1a) and methyl dichloroacetate (1b), to the corresponding cross-coupling products, such as substituted styrene 3 and methyl acrylates 4 derivatives, under mild reaction conditions in THF. The E-isomer of the corresponding alkenes was obtained stereoselectively in good-to-excellent yields. The reaction serves as a very convenient one-pot procedure.

Age-related changes in nicotinic acetylcholine receptor (nAChR) subunit alpha4 and beta2 messenger RNA (mRNA) expression in the postmortem human frontal cortex and hippocampus was investigated using the reverse transcription-polymerase chain reaction (RT-PCR). In the frontal cortex, both alpha4 and beta2 subunit mRNA expression decreased with age. In the hippocampus, alpha4 subunit mRNA expression was unaltered, while beta2 subunit mRNA expression significantly decreased with age. These findings suggest that nAChR transcription decreases during aging with differing vulnerability between subunits and brain regions, which could in part contribute to the reduction in cognitive functions seen in the elderly.

Expression of messenger RNAs (mRNAs) encoding the D1 and D2 dopamine receptors as a function of age was determined in the human putamen using the reverse transcription-polymerase chain reaction (RT-PCR). In cases without multiple small infarcts (status lacunaris) in the putamen, D1 mRNA expression was unaltered, while D2 mRNA expression significantly decreased with age. Both D1 and D2 mRNA expression was lower in cases with status lacunaris. The reduction in D1 receptors primarily located on striatonigral neurons or D2 receptors primarily located on striatopallidal neurons may inhibit thalamocortical neurons. The decreased transcription of D1 and D2 receptor genes may in part account for increased susceptibility to hypokinetic disorders in the elderly.

KF/Al(2)O(3) was found to be an efficient base for the reaction of imines with chloroform in acetonitrile to give gem-dichloroaziridines 2 in moderate to high yields. The KF/Al(2)O(3)-promoted dichloroaziridination can be carried out with simple workup, tolerates a variety of functional groups present in the imines, and proceeds smoothly with a smaller amount of carbene source.

Carbonylation of o-aminobenzonitriles (I) with CO2 in the presence of DBU bicarbonate salt at elevated temperatures affords quinazolinediones (III) in good to excellent yields.

The compound (III) is the stable equivalent to the instable compound (I), which is a raw material of ZYLON.

Facile synthesis of cyclic ethers from dihalo compounds on alumina has been accomplished in good yields. The reactions proceeded smoothly both in refluxing hexane and by microwave irradiation in the absence of solvent. Inaddition to being an organic-solvent-free operation, it also entails a short reaction time.

A Se-catalyzed carbonylation/oxidation sequence allows the conversion of diamines, primary and secondary amines into the corresponding urea derivatives.

Efficient oxidation system using reusable vanadyl(IV) sulfate catalyst was established. Toluenes were easily oxidized under molecular oxygen (0.1 MPa) at 100 °C catalyzed by vanadyl(IV) sulfate to afford the corresponding benzoic acids in excellent yields. The recovered catalyst could be reused without loss of activity.

The glycerol carbonate synthesis from glycerol, which is an inevitable by-product of biodiesel production, was established. By combined sulfur-assisted carbonylation of glycerol under 1.0 MPa of carbon monoxide at 80°C in DMF with oxidation by copper bromide(II), a facile synthetic method for glycerol carbonate in good yield was developed. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:99–102, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20583

Tetrakis(triphenylphosphine)platinum(0) (Pt(PPh3)4) in the presence of aromatic thiols exhibits an excellent catalytic activity toward the carbonylative lactonization of 5-hydroxy-1-pentyne with ca...

A combination of zinc metal and a catalytic amount of chlorotrimethylsilane has been found to promote the transformation of various aldehydes and ketones with gem-dichloro compounds, such as benzylidene dichloride (1a) and methyl dichloroacetate (1b), to the corresponding cross-coupling products, such as substituted styrene 3 and methyl acrylates 4 derivatives, under mild reaction conditions in THF. The E-isomer of the corresponding alkenes was obtained stereoselectively in good-to-excellent yields. The reaction serves as a very convenient one-pot procedure.

Facile synthesis of cyclic ethers from dihalo compounds on alumina has been accomplished in good yields. The reactions proceeded smoothly both in refluxing hexane and by microwave irradiation in the absence of solvent. Inaddition to being an organic-solvent-free operation, it also entails a short reaction time.

Treatment of acid chlorides (2) with allyl chlorides (1) in the presence of zinc dust and a catalytic amount of chlorotrimethylsilane (TMSCl) in THF brought about highly facile and effective coupling to give the corresponding gem-bisallylation products, 4-hydroxy-penta-1,6-dienes (3), in good to excellent yields. These reactions are assumed to proceed through allylzinc intermediates generated in situ.

The glycerol carbonate synthesis from glycerol, which is an inevitable by-product of biodiesel production, was established. By combined sulfur-assisted carbonylation of glycerol under 1.0 MPa of carbon monoxide at 80°C in DMF with oxidation by copper bromide(II), a facile synthetic method for glycerol carbonate in good yield was developed. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:99–102, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20583

The first example of cyclic urea synthesis from secondary amines by the use of sulfur-assisted carbonylation and oxidation was established. By combined sulfur-assisted carbonylation of secondary α,ω-diamines under an ambient pressure of carbon monoxide at 20°C with oxidation by molecular oxygen (0.1 MPa, 20°C), a facile synthetic method for N,N′-dialkyl cyclic ureas including 1,3-dimethyl-2-imidazolidinone was developed. © 2009 Wiley Periodicals, Inc. Heteroatom Chem 20:64–68, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20508

A solvent-free carbonylation and oxidation system aimed at green and sustainable chemistry was developed. With these reactions, an environmentally benign synthesis of urea derivatives could be carried out in good to excellent yields from primary amines and sulfur at ambient pressure of carbon monoxide and oxy-gen. For example, N, N′-dioctylurea was prepared in 99% yield from two equivalents octylamine and one equivalent sulfur in the presence of carbon monoxide (1 atm) at 80 °C and oxygen (1 atm) at room temperature, in the complete absence of solvent.