Thermal stability and oxidation characteristics of α-pinene, β-pinene and α-pinene/β-pinene mixture

Turpentine is a renewable resource, has good combustion performance, and is considered to be a fuel or promising additive to diesel fuel. This is very important for the investigation of thermal stability and energy oxidation characteristics, because evaluation of energy or fuel quality assurance and use safety are necessary. The main components of turpentine are α-pinene and β-pinene, which have unsaturated double bonds and high chemical activity. By investigating their thermal stability and oxidation reaction characteristics, we know the chemical thermal properties and thermal explosion hazard of turpentine. In this present study, the thermal stability and oxidation characteristics of α-pinene, β-pinene and α-pinene/β-pinene mixture were investigated using a high sensitivity accelerating rate calorimeter (ARC) and C80 calorimeter. The important parameters of oxidation reaction and thermal stability were obtained from the temperature, pressure and exothermic behavior in chemical reaction. The results show that α-pinene and β-pinene are thermally stable without chemical reaction under a nitrogen atmosphere even when the temperature reaches 473 K. The initial exothermic temperature of the two pinenes and their mixture is 333–338 K, and the heat release (−ΔH) of their oxidation is 2745–2973 J g⁻¹. The oxidation activation energy (E_a) of α-pinene, β-pinene and α-pinene/β-pinene mixture is 116.25 kJ mol⁻¹, 121.85 kJ mol⁻¹, and 115.95 kJ mol⁻¹, respectively. There are three steps in the oxidation of pinenes: the first is the induction period of the oxidation reaction; the second is the main oxidation stage, and the pressure is reduced; the third is thermal decomposition to produce gas.

Turpentine is a renewable resource, has good combustion performance, and is considered to be a fuel or promising additive to diesel fuel.     

T Cell Receptor–γ/δ Cells Protect Mice from Herpes Simplex Virus Type 1–induced Lethal Encephalitis

Increased numbers of T cell receptor (TCR)-γ/δ cells have been observed in animal models of influenza and sendai virus infections, as well as in patients infected with human immunodeficiency virus and herpes simplex virus type 1 (HSV-1). However, a direct role for TCR-γ/δ cells in protective immunity for pathogenic viral infection has not been demonstrated. To define the role of TCR-γ/δ cells in anti–HSV-1 immunity, TCR-α^−/− mice treated with anti– TCR-γ/δ monoclonal antibodies or TCR-γ/δ × TCR-α/β double-deficient mice were infected with HSV-1 by footpad or ocular routes of infection. In both models of HSV-1 infection, TCR-γ/δ cells limited severe HSV-1–induced epithelial lesions and greatly reduced mortality by preventing the development of lethal viral encephalitis. The observed protection resulted from TCR-γ/δ cell–mediated arrest of both viral replication and neurovirulence. The demonstration that TCR-γ/δ cells play an important protective role in murine HSV-1 infections supports their potential contribution to the immune responses in human HSV-1 infection. Thus, this study demonstrates that TCR-γ/δ cells may play an important regulatory role in human HSV-1 infections.     

The Ag-promoted α-C–H arylation of alcohols

We herein report the functionalization of α-C–H in alcohols through cross-dehydrogenative coupling reactions. Selectfluor was used as a mild oxidant. In situ-generated HF participated in the reaction and no external strong acid was necessary. A variety of heteroaryl-substituted alcohols were achieved with good yields and with good functional group tolerance.

We herein report the functionalization of α-C–H in alcohols through cross-dehydrogenative coupling reactions.

Alcohols are one of the most important types of compounds, because they exist universally in bioactive molecules and are also found in nature in the form of sugars, steroids, etc. Furthermore, alcohols can be used as versatile building blocks, and be transformed into other functional groups. The synthesis of alcohols is a classic topic in organic chemistry. Late-stage functionalization has attracted the interest of chemists because in this way complex molecules could be modified. In particular, functionalization of C–H is a very efficient way to build various structures, as pre-functionalization here is not needed. Thus, transformation of C–H in alcohols is a direct method to prepare diverse alcohols from simple molecules.During the past several decades, activations of the α sp³ C–H groups of alcohols have been achieved through radical-involved processes. In the early research, functionalizations of α C–H groups in alcohols were always initiated by light or di-tert-butyl peroxide, and the generated radicals could add to alkenes, affording alkylated alcohols.¹ This reaction was developed by Duan to construct hydroxyl-containing oxindoles through a tandem addition/cyclization reaction.² Also, amino alcohols were prepared through addition of radicals generated from alcohols to unactivated alkenes.³ Reactions catalyzed by metals such as Rh,⁴ Fe,⁵ Cu and Co⁶ have also been applied. In 2009, addition of such radicals to alkynes was reported. Homoallylic alcohols were prepared using simple alcohol molecules.⁷ The reactions of alcohols and cinnamic acids were also reported and allylic alcohols were obtained.⁸ However, arylations of the α C–H in alcohols have attracted much interest because such structures are present in many bioactive molecules (Fig. 1). Great efforts have been expended to the synthesis of arylated alcohols. In 2014, Liu reported the reaction of alcohol molecules and isocyanide, and various alkyl-substituted phenanthridines were achieved.⁹Open in a separate windowFig. 1Bioactive molecules containing alcoholic hydroxyl groups.Cross-dehydrogenative coupling reactions have been the focus of many researchers and have been shown to be powerful and convenient tools in organic synthesis.¹⁰ The activation of the C–H groups in two molecules allows application of starting materials without further functionalization. This simple process with high atomic economy provides an ideal transformation for the preparation of various target compounds. The Minisci reaction has been widely explored since the 1960s. Palmer and McIntyre first reported the hydroxymethylation of quinolone in the presence of hydroxylamine-O-sulphonic acid (HSA).¹¹ Minisci further developed an Fe-catalyzed process that resulted in good yields.¹² PdCl₂ (ref. 13) and TiCl₃ (ref. 14) were also shown to be efficient catalysts for the Minisci reaction. Metal-free reactions initiated by TBHP¹⁵ and M₂S₂O₈ (M = Na, K, NH₄)¹⁶ have also been developed. Very recently, as visible light-promoted processes find applications in organic synthesis, visible light-induced Minisci reactions have been reported.¹⁷ However, a strong oxidant, external acid, and complex system are always needed for these reactions. In our research, we found that Selectfluor could be used as a mild oxidant for the functionalizations of C–H groups in ethers, and the HF generated in situ could be made to participate in the reaction process.¹⁸ Herein, we report an Ag/Selectfluor-catalyzed Minisci reaction, in which Selectfluor was used as a mild oxidant and no external acid was necessary (Scheme 1).Open in a separate windowScheme 1Arylations of α sp³ C–H groups in alcohols.We chose quinaldine as the model substrate and carried out the reactions (

Selection and Characterization of β-Lactam–β-Lactamase Inactivator-Resistant Mutants following PCR Mutagenesis of the TEM-1 β-Lactamase Gene

Mechanism-based inactivators of β-lactamases are used to overcome the resistance of clinical pathogens to β-lactam antibiotics. This strategy can itself be overcome by mutations of the β-lactamase that compromise the effectiveness of their inactivation. We used PCR mutagenesis of the TEM-1 β-lactamase gene and sequenced the genes of 20 mutants that grew in the presence of ampicillin-clavulanate. Eleven different mutant genes from these strains contained from 1 to 10 mutations. Each had a replacement of one of the four residues, Met69, Ser130, Arg244, and Asn276, whose substitutions by themselves had been shown to result in inhibitor resistance. None of the mutant enzymes with multiple amino acid substitutions generated in this study conferred higher levels of resistance to ampicillin alone or ampicillin with β-lactamase inactivators (clavulanate, sulbactam, or tazobactam) than the levels of resistance conferred by the corresponding single-mutant enzymes. Of the four enzymes with just a single mutation (Ser130Gly, Arg244Cys, Arg244Ser, or Asn276Asp), the Asn276Asp β-lactamase conferred a wild-type level of ampicillin resistance and the highest levels of resistance to ampicillin in the presence of inhibitors. Site-directed random mutagenesis of the Ser130 codon yielded no other mutant with replacement of Ser130 besides Ser130Gly that produced ampicillin-clavulanate resistance. Thus, despite PCR mutagenesis we found no new mutant TEM β-lactamase that conferred a level of resistance to ampicillin plus inactivators greater than that produced by the single-mutation enzymes that have already been reported in clinical isolates. Although this is reassuring, one must caution that other combinations of multiple mutations might still produce unexpected resistance.     

The CD3-γδε and CD3-ζ/η Modules Are Each Essential for Allelic Exclusion at the T Cell Receptor β Locus but Are Both Dispensable for the Initiation of V to (D)J Recombination at the T Cell Receptor–β, –γ, and –δ Loci

The pre–T cell receptor (TCR) associates with CD3-transducing subunits and triggers the selective expansion and maturation of T cell precursors expressing a TCR-β chain. Recent experiments in pre-Tα chain-deficient mice have suggested that the pre-TCR may not be required for signaling allelic exclusion at the TCR-β locus. Using CD3-ε– and CD3-ζ/η–deficient mice harboring a productively rearranged TCR-β transgene, we showed that the CD3-γδε and CD3-ζ/η modules, and by inference the pre-TCR/CD3 complex, are each essential for the establishment of allelic exclusion at the endogenous TCR-β locus. Furthermore, using mutant mice lacking both the CD3-ε and CD3-ζ/η genes, we established that the CD3 gene products are dispensable for the onset of V to (D)J recombination (V, variable; D, diversity; J, joining) at the TCR-β, TCR-γ, and TCR-δ loci. Thus, the CD3 components are differentially involved in the sequential events that make the TCR-β locus first accessible to, and later insulated from, the action of the V(D)J recombinase.     

Hydrophilic and organophilic pervaporation of industrially important α,β and α,ω-diols

The distillation-based purification of α,β and α,ω-diols is energy and resource intensive, as well as time consuming. Pervaporation separation is considered to be a remarkable energy efficient membrane technology for purification of diols. Thus, as a core pervaporation process, hydrophilic polyvinyl alcohol (PVA) membranes for the removal of water from 1,2-hexanediol (1,2-HDO) and organophilic polydimethylsiloxane–polysulfone (PDMS–PSF) membranes for the removal of isopropanol from 1,5 pentanediol (1,5-PDO) were employed. For 1,2-HDO/water separation using a feed having a 1 : 4 weight ratio of 1,2-HDO/water, the membrane prepared using 4 vol% glutaraldehyde (GA4) showed the best performance, yielding a flux of 0.59 kg m⁻² h⁻¹ and a separation factor of 175 at 40 °C. In the organophilic pervaporation separation of the 1,5-PDO/IPA feed having a 9 : 1 weight ratio of components, the PDMS membrane prepared with a molar ratio of TEOS alkoxy groups to PDMS hydroxyl groups of 70 yielded a flux of 0.12 kg m⁻² h⁻¹ and separation factor of 17 638 at 40 °C. Long term stability analysis found that both hydrophilic (PVA) and organophilic (PDMS) membranes retained excellent pervaporation output over 18 days'' continuous exposure to the feed. Both the hydrophilic and organophilic membranes exhibited promising separation performance at elevated operating conditions, showing their great potential for purification of α,β and α,ω-diols.

The distillation-based purification of α,β and α,ω-diols is energy and resource intensive, as well as time consuming.     

Oxygen Equilibrium Characteristics of Abnormal Hemoglobins: Hirose (α2β237Ser), L Ferrara (α247Glyβ2), Broussais (α290Asnβ2), and Dhofar (α2β258Arg)

The oxygen equilibrium characteristics of four structural variants of hemoglobin A were correlated with their amino acid substitutions.Hemoglobin Dhofar, in which the proline at E2(58)beta is replaced by arginine, had normal oxygen equilibrium characteristics.Hemoglobin L Ferrara. in which the aspartic acid at CD5(47)alpha is replaced by glycine, and hemoglobin Broussais, in which the lysine at FG2(90)alpha is replaced by asparagine, both showed a slightly elevated oxygen affinity; nevertheless both demonstrated a normal heme-heme interaction and a normal Bohr effect.Hemoglobin Hirose, in which the tryptophan at C3 (37)beta is replaced by serine, showed abnormalities of all oxygen equilibrium characteristics; i.e., increased oxygen affinity, diminished heme-heme interaction, and reduced Bohr effect.These results suggest that aspartic acid at CD5(47)alpha and lysine at FG2(90)alpha are involved in the function of the hemoglobin molecule, despite the fact that these positions are not located directly in the heme or the alpha-beta-contact regions.Tryptophan at C3(37)beta is located at contact between alpha(1)- and beta(2)-subunits. It is suggested that the substitution by serine might disturb the quarternary structure of the mutant hemoglobin molecule during transition from oxy-form to deoxy-form resulting in an alteration of the heme function.     

K2S2O8-promoted C–Se bond formation to construct α-phenylseleno carbonyl compounds and α,β-unsaturated carbonyl compounds

A novel K₂S₂O₈-promoted C–Se bond formation from cross-coupling under neutral conditions has been developed. A variety of aldehydes and ketones react well using K₂S₂O₈ as the oxidant in the absence of catalyst and afford desired products in moderate to excellent yields. This protocol provides a very simple route for the synthesis of α-phenylseleno carbonyl compounds and α,β-unsaturated carbonyl compounds.

K₂S₂O₈-promoted C–Se bond formation from the cross-coupling of C(sp³)–H bond adjacent to carbonyl group with diphenyl diselenide under metal-free conditions.

Selenium (Se) is an essential trace mineral nutrient that exerts multiple and complex effects on human health.¹ Selenium has been widely applied in a variety of fields such as the organic synthesis, catalysis, agriculture chemistry, materials science and even the environment protection.² Se-containing compounds have attracted vast interest because of their extensive bioactive functions and important roles in chemical reactions.³ As metabolites of Se in humans, phenylseleno (–SePh) groups are extremely important.⁴ It has been reported that SePh-containing compounds can act as redox agents suitable for targeting cancer cells or play a role in steroid chemistry. Several reported SePh-containing compounds that imitate glutathione peroxidase, like ebselen,⁵ that act as redox agents suitable for targeting cancer cells (naphthoquinone derivatives)⁶ or are important in steroid chemistry (estrogen derivatives)⁷ are shown in Fig. 1. Furthermore, α-phenylseleno carbonyl compounds have a special place since these substances also serve as versatile intermediates in organic synthesis.⁸ They can be converted into the corresponding synthetically useful α,β-unsaturated aldehydes or ketones through oxidation by H₂O₂ or NaIO₄ followed by selenoxide elimination⁹ and Sahani''s group has used α-phenylselanyl ketones as substrates to obtain α-arylated ketones through organic photoredox catalysis.¹⁰Open in a separate windowFig. 1Examples of Se-containing biologically active compounds.Oxidative functionalization of carbonyl compounds has been known since 1935 (ref. 11) and was studied further by Saegusa, Mislow, Baran and others.¹² While there generally exist various means, either direct or indirect, of accessing particular target molecules, in order to continue to advance this field, we must constantly study more efficient and green methods. Currently, several procedures have been developed for the preparation of α-phenylseleno aldehydes and ketones. One typical method to synthesize such compounds is by using an enolate coupling reaction.¹³ This approach suffers from the use of a stoichiometric amount of a strong base and metal oxidant to produce the enolate followed by an oxidative coupling reaction (see Scheme 1). In 2015, Yan''s group demonstrated that with the participation of a suitable oxidant, ketones can undergo direct oxidation functionalization.¹⁴ Despite the improvement of not using strong base, it still needed multiple times the amount of metal-free oxidants. In addition, K₂S₂O₈ was found to be a useful oxidant in oxidative reactions because of its characteristics of easy availability, good stability, and low toxicity. Thus, studies focusing on the development of K₂S₂O₈-mediated oxidative reactions meet the requirement of sustainable chemistry.¹⁵ Based on our research on the functionalization of the C(sp³)–H bond, and in connection to our continued interest in developing efficient metal-free functionalization strategies,¹⁶ herein we report an efficient K₂S₂O₈-mediated C–Se bond formation for the synthesis of α-phenylseleno carbonyl compounds.Open in a separate windowScheme 1Synthesis of α-phenylseleno carbonyl compounds (M = metal).Initially, we utilized acetone (1a) as a standard substrate to evaluate the coupling of C(sp³)–H bonds adjacent to a carbonyl group with diphenyl diselenide (2). Treatment of 1a with 1.0 equiv. of (NH₄)₂S₂O₈ in DMSO at 80 °C under air for 3 h afforded the desired product 3a in 29% yield (17 Then various reaction parameters were screened, including the oxidant, solvent, and temperature. A range of oxidants such as PhI(OAc)₂, IBX, Ag₂O, Na₂S₂O₈, K₂S₂O₈, and oxone were tested, and K₂S₂O₈ showed the highest efficiency (entries 2–7). The solvent also played a key role in this transformation. The product yield decreased when DMSO was replaced by DMF, DMA, CH₃CN or EtOH (entries 8–11). Taking the place of air with argon, the reaction gave the desired product 3a in a similar yield (87%) (entry 12). Notably, a similar yield of 3a was obtained by lowering the amount of K₂S₂O₈ to 0.5 equiv. (entry 13). However, a further decrease of the oxidant amount resulted in a lower yield of 3a (entry 14). The reaction temperature had little influence on the reaction efficiency, and 80 °C was still the best choice (entries 15 and 16). A control experiment revealed that K₂S₂O₈ was necessary for the success of this reaction (entry 17).Optimization of the reaction conditions^a,b

In(OTf)3-catalyzed intramolecular hydroarylation of α-phenylallyl β-ketosulfones – synthesis of sulfonyl 1-benzosuberones and 1-tetralones

In(OTf)₃-catalyzed intramolecular hydroarylation of α-phenylallyl β-ketosulfones provides sulfonyl 1-benzosuberones and 1-tetralones in moderate to good yields in refluxing (CH₂Cl)₂ under open-vessel and easy-operation reaction conditions. A plausible mechanism is proposed and discussed. This highly regioselective protocol provides an atom-economic ring-closure route.

In(OTf)₃-catalyzed intramolecular hydroarylation of α-phenylallyl β-ketosulfones provides sulfonyl 1-benzosuberones and 1-tetralones in moderate to good yields in refluxing (CH₂Cl)₂ under open-vessel and easy-operation reaction conditions.     

IL-1β–driven osteoclastogenic Tregs accelerate bone erosion in arthritis

IL-1β is a proinflammatory mediator with roles in innate and adaptive immunity. Here we show that IL-1β contributes to autoimmune arthritis by inducing osteoclastogenic capacity in Tregs. Using mice with joint inflammation arising through deficiency of the IL-1 receptor antagonist (Il1rn^–/–), we observed that IL-1β blockade attenuated disease more effectively in early arthritis than in established arthritis, especially with respect to bone erosion. Protection was accompanied by a reduction in synovial CD4⁺Foxp3⁺ Tregs that displayed preserved suppressive capacity and aerobic metabolism but aberrant expression of RANKL and a striking capacity to drive RANKL-dependent osteoclast differentiation. Both Il1rn^–/– Tregs and wild-type Tregs differentiated with IL-1β accelerated bone erosion upon adoptive transfer. Human Tregs exhibited analogous differentiation, and corresponding RANKL^hiFoxp3⁺ T cells could be identified in rheumatoid arthritis synovial tissue. Together, these findings identify IL-1β–induced osteoclastogenic Tregs as a contributor to bone erosion in arthritis.     

The SIRPα–CD47 immune checkpoint in NK cells

Here we report on the existence and functionality of the immune checkpoint signal regulatory protein α (SIRPα) in NK cells and describe how it can be modulated for cell therapy. NK cell SIRPα is up-regulated upon IL-2 stimulation, interacts with target cell CD47 in a threshold-dependent manner, and counters other stimulatory signals, including IL-2, CD16, or NKG2D. Elevated expression of CD47 protected K562 tumor cells and mouse and human MHC class I–deficient target cells against SIRPα⁺ primary NK cells, but not against SIRPα⁻ NKL or NK92 cells. SIRPα deficiency or antibody blockade increased the killing capacity of NK cells. Overexpression of rhesus monkey CD47 in human MHC-deficient cells prevented cytotoxicity by rhesus NK cells in a xenogeneic setting. The SIRPα–CD47 axis was found to be highly species specific. Together, the results demonstrate that disruption of the SIRPα–CD47 immune checkpoint may augment NK cell antitumor responses and that elevated expression of CD47 may prevent NK cell–mediated killing of allogeneic and xenogeneic tissues.     

Visible light-induced oxidative α-hydroxylation of β-dicarbonyl compounds catalyzed by ethylenediamine–copper(ii)

We have developed an efficient oxidative α-hydroxylation of β-keto esters with firstly using the structurally simple ethylenediamine–copper(ii) as a catalyst for β-keto esters activation and using visible light as the driving force for generating more active singlet oxygen (¹O₂) from triplet state oxygen (³O₂) in the air, providing a series of α-hydroxy β-keto esters in excellent yields (up to 99%) under extremely low photosensitizer loading (0.01 mol%) and catalyst loading (1 mol%) within a short time. Moreover, the gram-scale synthesis showed the practical utility of this protocol.

An efficient visible light-induced oxidative α-hydroxylation of β-dicarbonyl compounds has been developed using structurally simple ethylenediamine–copper(ii) as a catalyst.     

Two New Antimetabolites of Biotin: α-Methyldethiobiotin and α-Methylbiotin

Two new antimetabolites of biotin were isolated from culture filtrates of Streptomyces lydicus: β-methyldethiobiotin and β-methylbiotin. ¹⁴C-biotin or ¹⁴C-pimelic acid was not incorporated into either of these antimetabolites by the growing culture. Neither of the compounds could substitute for the biotin requirement in Saccharomyces cerevisiae. Both compounds had a strong and rather specific antimicrobial effect against mycobacteria. Their antimicrobial activities were reversed by biotin. Both compounds had an affinity for avidin.     

Equal synthesis of α- and β-globin chains in erythroid precursors in heterozygous β-thalassemia

In patients with heterozygous beta-thalassemia, the beta/alpha synthetic ratio in marrow erythroid cells incubated in vitro is 1, whereas in reticulocytes the ratio is 0.5. These ratios reflect the equal synthesis of the two chains on the polyribosomes of the bone marrow and unequal synthesis on the polyribosomes of the peripheral blood reticulocytes. alpha- and beta-chain synthesis is also equal in marrow cells in vivo. Equal synthesis is probably due both to a decrease in alpha-chain synthesis and an increase in beta-chain synthesis in bone marrow erythroid cells and may contribute to the absence of overt hemolysis due to excess alpha-globin chain accumulation in heterozygous beta-thalassemia.     

Direct β-selectivity of α,β-unsaturated γ-butyrolactam for asymmetric conjugate additions in an organocatalytic manner

The β-selective asymmetric addition of γ-butyrolactam with cyclic imino esters catalyzed by a bifunctional chiral tertiary amine has been developed, which provides an efficient access to optically active β-position functionalized pyrrolidin-2-one derivatives in both high yield and enantioselectivity (up to 78% yield and 95 : 5 er). This is the first catalytic method to access chiral β-functionalized pyrrolidin-2-one via a direct organocatalytic approach.

The asymmetric addition of γ-butyrolactam with cyclic imino esters catalyzed by (DHQD)₂AQN has been developed, which provides an access to β-position functionalized pyrrolidin-2-one derivatives in high levels yield and enantioselectivity.

Metal-free organocatalytic asymmetric transformations have successfully captured considerable enthusiasm of chemists as powerful methods for the synthesis of various kinds of useful chiral compounds ranging from the preparation of biologically important molecules through to novel materials.¹ Chiral pyrrolidin-2-ones have been recognized as important structural motifs that are frequently encountered in a variety of biologically active natural and synthetic compounds.² In particular, the β-position functionalized pyrrolidin-2-one backbones, which can serve as key synthetic precursors for inhibitory neurotransmitters γ-aminobutyric acids (GABA),³ selective GABA_B receptor agonists⁴ as well as antidepressant rolipram analogues,⁵ have attracted a great deal of attention. Therefore, the development of highly efficient, environmentally friendly and convenient asymmetric synthetic methods to access these versatile frameworks is particularly appealing.As a direct precursor to pyrrolidin-2-one derivatives, recently, α,β-unsaturated γ-butyrolactam has emerged as the most attractive reactant in asymmetric organometallic or organocatalytic reactions for the synthesis of chiral γ-position functionalized pyrrolidin-2-ones (Scheme 1). These elegant developments have been achieved in the research area of catalytic asymmetric vinylogous aldol,⁶ Mannich,⁷ Michael⁸ and annulation reactions⁹ in the presence of either metal catalysts or organocatalysts (a, Scheme 1). These well-developed catalytic asymmetric methods have been related to the γ-functionalized α,β-unsaturated γ-butyrolactam to date. However, in sharp contrast, the approaches toward introducing C-3 chirality at the β-position of butyrolactam through a direct catalytic manner are underdeveloped (b, Scheme 1)¹⁰ in spite of the fact that β-selective chiral functionalization of butyrolactam can directly build up α,β-functionalized pyrrolidin-2-one frameworks.Open in a separate windowScheme 1Different reactive position of α,β-unsaturated γ-butyrolactam in catalytic asymmetric reactions.So far, only a few metal-catalytic enantioselective β-selective functionalized reactions have been reported. For examples, a rhodium/diene complex catalyzed efficient asymmetric β-selective arylation^10a and alkenylation^10b have been reported by Lin group (a, Scheme 2). Procter and co-workers reported an efficient Cu(i)–NHC-catalyzed asymmetric silylation of unsaturated lactams (b, Scheme 2).^10c Despite these creative works, considerable challenges still exist in the catalytic asymmetric β-selective functionalization of γ-butyrolactam. First, the scope of nucleophiles is limited to arylboronic acids, potassium alkenyltrifluoroborates and PhMe₂SiBpin reagents. Second, the catalytic system and activation mode is restricted to metal/chiral ligands. To our knowledge, an efficient catalytic method to access chiral β-functionalized pyrrolidin-2-one via a direct organocatalytic approach has not yet been established. Therefore, the development of organocatalytic asymmetric β-selective functionalization of γ-butyrolactam are highly desirable. In conjunction with our continuing efforts in building upon chiral precedents by using chiral tertiary amine catalytic system,¹¹ we rationalized that the activated α,β-unsaturated γ-butyrolactam might serve as a β-position electron-deficient electrophile. This γ-butyrolactam may react with a properly designed electron-rich nucleophile to conduct an expected β-selective functionalized reaction of γ-butyrolactam under a bifunctional organocatalytic fashion, while avoiding the direct γ-selective vinylogous addition reaction or β,γ-selective annulation as outlined in Scheme 2. Herein we report the β-selective asymmetric addition of γ-butyrolactam with cyclic imino esters¹² catalyzed by a bifunctional chiral tertiary amine, which provides an efficient and facile access to optically active β-position functionalized pyrrolidin-2-one derivatives with both high diastereoselectivity and enantioselectivity.Open in a separate windowScheme 2β-Selective functionalization of γ-butyrolactam via metal- (previous work) or organo- (this work) catalytic approach.To begin our initial investigation, several bifunctional organocatalysts¹³ were firstly screened to evaluate their ability to promote the β-selective asymmetric addition of γ-butyrolactam 2a with cyclic imino ester 3a in the presence of 15 mol% of catalyst loading at room temperature in CH₂Cl₂ (entries 1–6, EntryCat.SolventYield^eer^f11aCH₂Cl₂70%40 : 6021bCH₂Cl₂<5%57 : 4331cCH₂Cl₂70%65 : 3541dCH₂Cl₂68%70 : 3051eCH₂Cl₂58%63 : 4761fCH₂Cl₂71%77 : 2371fDCE72%80 : 2081fCHCl₃70%80 : 2091fMTBE68%79 : 21101fToluene63%78 : 22111fTHF45%76 : 24121fMeOH32%62 : 3813^b1fDCE : MTBE75%87 : 1314^c1fDCE : MTBE72%87 : 1315^d1fDCE : MTBE70%85 : 15Open in a separate window^aReaction conditions: unless specified, a mixture of 2a (0.2 mmol), 3a (0.3 mmol) and a catalyst (15 mmol%) in a solvent (2.0 mL) was stirred at rt. for 48 h.^bThe reaction was carried out in 2.2 mL a mixture of dichloroethane and methyl tert-butyl ether (volume ratio = 10 : 1).^cThe reaction was carried out in 2.2 mL a mixture of dichloroethane and methyl tert-butyl ether (volume ratio = 10 : 1) for 24 h.^dThe reaction was carried out in 2.2 mL a mixture of dichloroethane and methyl tert-butyl ether (volume ratio = 10 : 1) and 10 mol% of catalyst was used.^eIsolated yields.^fDetermined by chiral HPLC, the product was observed with >99 : 1 dr by ¹H NMR and HPLC. Configuration was assigned by X-ray crystal data of 4a.The results of experiments under the optimized conditions that probed the scope of the reaction are summarized in Scheme 3. The catalytic β-selective asymmetric addition of γ-butyrolactam 2a with cyclic imino esters 3a in the presence of 15 mol% (DHQD)₂AQN 1f was performed. A variety of phenyl-substituted cyclic imino esters including those bearing electron-withdrawing and electron-donating substituents on the aryl ring, heterocyclic were also examined. The electron-neutral, electron-rich, or electron-deficient groups on the para-position of phenyl ring of the cyclic imino esters afforded the products 4a–4m in 57–75% yields and 82 : 18 to 95 : 5 er values. It appears that either an electron-withdrawing or an electron-donating at the meta- or ortho-position of the aromatic ring had little influence on the yield and stereoselectivity. Similar results on the yield and enantioselectivities were obtained with 3,5-dimethoxyl substituted cyclic imino ester (71% yield and 91 : 9 er). It was notable that the system also demonstrated a good tolerance to naphthyl substituted imino ester (78% yield and 92 : 8 er value). The 2-thienyl substituted cyclic imino ester proceeded smoothly under standard conditions as well, which gave the desired product 4p in good enantioselectivity (88 : 12 er), although yield was slightly lower. However, attempts to extend this methodology to aliphatic-substituted product proved unsuccessful due to the low reactivity of the substrate 3q. It is worth noting that the replacement of Boc group with 9-fluorenylmethyl, tosyl or benzyl group as the protection, no reaction occurred. The absolute and relative configurations of the products were unambiguously determined by X-ray crystallography (4a, see the ESI^†).Open in a separate windowScheme 3Substrate scope of the asymmetric reaction of α,β-unsaturated γ-butyrolactam 2 to cyclic imino esters 3.^{a a}Reaction conditions: unless specified, a mixture of 2 (0.2 mmol), 3 (0.3 mmol) and 1f (15.0 mmol%) in 2.2 mL a mixture of dichloroethane and methyl tert-butyl ether (volume ratio = 10 : 1) was stirred at rt. ^bIsolated yields. ^cDetermined by chiral HPLC, all products were observed with >99 : 1 dr by ¹H NMR and HPLC. Configuration was assigned by comparison of HPLC data and X-ray crystal data of 4a.We then examined the substrate scope of the imide derivatives (Scheme 4). Investigations with maleimides 4r–4u gave 48–61% yield of corresponding products as lower er and dr values than most of γ-butyrolactams. As for methyl substituted maleimides, the reaction failed to give any product.Open in a separate windowScheme 4Substrate scope of the asymmetric reaction of maleimides to cyclic imino esters.^{a a}Reaction conditions: unless specified, a mixture of 2 (0.2 mmol), 3 (0.3 mmol) and 1f (15.0 mmol%) in 2.2 mL a mixture of dichloroethane and methyl tert-butyl ether (volume ratio = 10 : 1) was stirred at rt. ^bIsolated yields. ^cDetermined by ¹H NMR and chiral HPLC.The chloride product 4a ((R)-tert-butyl 4-((R)-3-((E)-(4-chlorobenzylidene)amino)-2-oxotetra hydrofuran-3-yl)-2-oxopyrrolidine-1-carboxylate) was recrystallized and the corresponding single crystal was subjected to X-ray analysis to determine the absolute structure. Based on this result and our previous work, a plausible catalytic mechanism involving multisite interactions was assumed to explain the high stereoselectivity of this process (Fig. 1). Similar to the conformation reported for the dihydroxylation and the asymmetric direct aldol reaction, the transition state structure of the substrate/catalyst complexes might be presumably in the open conformation. The acidic α-carbon atom of cyclic imino ester 3a could be activated by interaction between the tertiary amine moiety of the catalyst and the enol of 3avia a hydrogen bonding. Moreover, the enolate of 3a in the transition state might be in part stabilized through the π–π stacking between the phenyl ring of 3a and the quinoline moiety. Consequently, the Re-face of the enolate is blocked by the left half of the quinidine moiety. The steric hindrance between the Boc group of 2a and the right half of the quinidine moiety make the Re-face of 2a face to the enolate of 3a. Subsequently, the attack of the incoming nucleophiles forms the Si-face of enolate of 3a to Re-face of 2a takes place, which is consistent with the experimental results.Open in a separate windowFig. 1Proposed transition state for the reaction.In conclusion, we have disclosed the β-selective asymmetric addition of γ-butyrolactam with cyclic imino esters catalyzed by a bifunctional chiral tertiary amine, which provides an efficient and facile access to optically active β-position functionalized pyrrolidin-2-one derivatives with high diastereoselectivity and enantioselectivity. To our knowledge, this is the first catalytic method to access chiral β-functionalized pyrrolidin-2-one via a direct organocatalytic approach. Current efforts are in progress to apply this new methodology to synthesize biologically active products.     

One-pot synthesis of α-aminophosphonates by yttrium-catalyzed Birum–Oleksyszyn reaction

For the first time, yttrium triflate was used as an efficient green catalyst for the synthesis of α-aminophosphonates through a one-pot three-component Birum–Oleksyszyn reaction. Under the action of this Lewis acid, enhancement of the yield and reaction chemoselectivity was provided by the achievement of an appropriate balance in the complex network of reactions.

For the first time, yttrium triflate was used as an efficient green catalyst for the synthesis of α-aminophosphonates through a one-pot three-component Birum–Oleksyszyn reaction.

Multicomponent reactions are commonly used to achieve molecular complexity. In particular, one-pot three-component reactions have been exploited for the synthesis of α-aminophosphonates. These organophosphorus compounds have attracted the attention of medicinal chemists due to their similarity to α-amino acids. They find application in agriculture as plant growth regulators¹ and herbicides,² in medicinal chemistry as antibacterial,^3,4 antiviral⁵ and antitumor agents,⁶ activity-based probes,⁷ and building blocks for peptides and proteins.⁸ Since the first preparation of α-aminophosphonates, reported in 1952 by Fields,⁹ various methods for their synthesis have been proposed.^10–16 Nowadays, one-pot three-component condensation of aldehyde, amine, and phosphite, catalyzed by an excess of acetic acid, is the most common method due to its simplicity and, in general, high yields of products.⁴ Application of Lewis acids as the catalyst instead of Brønsted acids was first reported in 1973 by Birum.¹⁷ The advantage of Lewis acids is their compatibility with acid-sensitive functional groups that, under typical conditions (glacial acetic acid) would be degraded.Condensation of aldehyde, carbamate, and triaryl phosphite has been named as Birum–Oleksyszyn reaction.¹⁸ Recently, a new biologically active α-aminophosphonate (UAMC-00050) was developed at the University of Antwerp.^19–21 This diarylphosphonate shows good inhibitory activity against urokinase plasminogen activator (uPA), an enzyme involved in several physiological processes, such as tissue remodeling.²² uPA can be also involved in the development of different diseases, for example, thrombolytic disorder,²³ cancer,²⁴ and eye diseases.²⁵ UAMC-00050 is currently under investigation for the treatment of irritable bowel syndrome²⁶ and dry eye disease.²¹ The key step of the synthesis of UAMC-00050, proposed by Joossens et al.,^19,21 involves Birum–Oleksyszyn reaction, catalyzed by Cu(OTf)₂ in acetonitrile, which, on a small scale, provides 20% yield of the product (Scheme 1). In current work, a new catalyst has been introduced for the Birum–Oleksyszyn reaction. For the first time, we report the use of yttrium salt in a one-pot three-component synthesis of α-aminophosphonates, which provides a remarkable improvement of the yield of product for the key step in the synthesis of UAMC-00050. The scope of the protocol has been demonstrated on a variety of aldehydes, phosphites, and carbamates.Open in a separate windowScheme 1Conditions for the preparation of intermediate 4 in the synthesis of UAMC-00050 (5).In the frame of the dry eye disease drug development (IT-DED3) project,²⁷ we have worked toward upscaling of the synthetic route and providing larger amounts of UAMC-00050 for more detailed research of its biological activity.During our attempts to upscale the key step to 3.0 g scale, we noticed a considerable decrease of the yield of product from 20% to 11%. In our view, the poor outcome of the process cannot be attributed to the Birum–Oleksyszyn reaction alone. The nature of substituents in the target molecule affects the overall efficiency of the transformation through both the main and a number of side reactions (Scheme 2). This three-component reaction involves unstable paracetamol phosphite 1, aliphatic aldehyde 2 bearing Boc-protected amino group, and benzyl carbamate 3 (Scheme 1). In general, aliphatic aldehydes are less reactive in Birum–Oleksyszyn reaction, which consequently requires a stronger catalyst or longer reaction time to achieve satisfactory yield of product.^15,28 The imine generated from the condensation of carbamate and aldehyde is highly reactive and can add a second molecule of carbamate forming aminal 7.²⁹ Compound 7 can participate in Arbuzov-type reactions,³⁰ if, as hypothesized, it is converted into reactive cation 13 by Brønsted²⁹ or Lewis acid.³¹ However, Lewis acid-catalyzed reactions of aminal 7 or its analogs and triaryl phosphites are not known.Open in a separate windowScheme 2Birum–Oleksyszyn reaction as the key step and possible side reactions in the synthesis of UAMC-00050.The presence of paracetamol moiety complicates the synthesis due to the lower stability of its phosphorus esters both in starting triaryl phosphite and in the formed α-aminophosphonate. In the reaction environment, they readily hydrolyze with one equivalent of water formed in the condensation of aldehyde 2 and the carbamate 3 generating diarylphosphite 9 and monoaryl side product 10.As previously reported, product 4 is stable in the presence of water.²¹ However, under the reaction conditions, hydrolysis proceeds with the help of the Lewis acid.³² With prolonged reaction time (i.e., 24 h) we noticed a decrease in the yield of product 4 almost in half compared to the yield obtained in the reaction performed for 4 h and formation of acid 10 as the major side product.Application of N-Boc-protected starting material is also challenging, since, in the presence of a Lewis acid catalyst, partial removal of the Boc group takes place and unprotected amino aldehyde 11 forms black-brown polymer 12 (Scheme 2).Improving the overall efficiency of the synthesis of α-aminophosphonate 4 requires simultaneous promotion of imine formation and Birum–Oleksyszyn reaction and suppression of unwanted hydrolysis and Boc group removal. In search for optimal conditions, we initiated screening of various acidic catalysts using equimolar ratio (1 : 1 : 1) of aldehyde 2, carbamate 3, and phosphite 1 with 10 mol% load of the catalyst in MeCN performing the reaction at room temperature for 4 h.¹⁹ Acetonitrile proved to be an optimal solvent for the preparation of 4, it is polar enough to dissolve all the starting materials, it is not a concern for the environment, like DCM, and it does not hydrolyze the product like protic solvents: MeOH, EtOH and H₂O.In EntryCatalystYield of product 4, %^bRatio 4/10Selectivity, %^c1AcOH^d00 : 10002TiCl₄844 : 66443ZrCl₄881 : 19814Cu(OTf)₂1176 : 24765BiCl₃1374 : 26746TfOH1382 : 18827Mg(OTf)₂1450 : 50508FeCl₃1568 : 32689LiOTf1585 : 158510Sc(OTf)₃1681 : 198111Et₂O·BF₃1676 : 247612Bi(NO₃)₃·5H₂O1976 : 247613Yb(OTf)₃2067 : 336714SnCl₄2257 : 435715ZnCl₂2281 : 198116La(OTf)₃2569 : 316917Bi(OTf)₃3176 : 247618AcOH3554 : 465419Y(OTf)₃4280 : 208020Y(OTf)₃^e1784 : 168421Y(OTf)₃^f3166 : 3466Open in a separate window^aReaction conditions: 1.0 equiv. of aldehyde 2, 1.0 equiv. of phosphite 1, 1.0 equiv. of benzyl carbamate 3 and 10 mol% of Lewis acid, anhydrous MeCN, under argon, RT, 4 h.^bIsolated yield.^cSelectivity expressed as a percent ratio of compounds 4 and 10.^dAcOH as a solvent.^e1.0 equiv. trimethyl orthoformate (TMOF).^f1.5 g of 4 Å MS.Although the yield of product 4 was low (13%), TfOH provided a much better stability of compound 4 toward the hydrolysis (82% of it survived vs. only 18% of the hydrolyzed 10). Lewis acids like TiCl₄, Cu(OTf)₂, ZnCl₂, and FeCl₃ are commonly used in three-component synthesis of α-aminophosphonates.^18,33–35 Triflate salts were included in the list because of their enhanced stability in the presence of water generated after the condensation of aldehyde 2 and carbamate 3.^36,37As reported in literature, phosphodiesters can be hydrolyzed by Lewis acids.^32,38 Paracetamol-containing phosphorus esters are much more sensitive to the presence of water compared to their alkyl analogs. Therefore, analysis of the catalyst efficiency can be carried out by using an additional parameter – selectivity for the formation of the target diester 4 compared to the proportion of the hydrolyzed monoester side product 10. This parameter is expressed as a percentage ratio of compounds 4 and 10, obtained from HPLC-UV assay with internal standard. Diagram with yield of product 4 on the horizontal axis and selectivity of the formation of compound 4 on the vertical axis is shown on Fig. 1.Open in a separate windowFig. 1Yield of product 4 (horizontal axis, percent) and selectivity of the formation of diaryl product 4 compared to monoaryl product 10 (vertical axis, percent ratio).For example, Lewis acids like TiCl₄, Mg(OTf)₂, and SnCl₄ hydrolyzed up to a half of diester 4 comprising the group with the lowest overall efficiency. On the other hand, LiOTf provided the best compatibility with diester 4 and the lowest degree of hydrolysis (85% of diester 4 preserved), but only a moderate yield of 15%. The two elements of group 1 and group 2 in catalysts LiOTf and Mg(OTf)₂ both provided low yield of product 4 (15% and 14%, respectively) but different selectivity, quite high for lithium (85%) and moderate for magnesium (50%).Three different salts of bismuth were tested, for all of which similar selectivity was registered (74–76%). However, quite large difference in yields of compound 4 was observed – 13% for BiCl₃, 19% for Bi(NO₃)₃·5H₂O, and 31% for Bi(OTf)₃. Eight triflate salts were screened and provided a wide range of yield and selectivity. Cu(OTf)₂ was the most ineffective in terms of yield, while Mg(OTf)₂ was the least selective toward the formation of product 4. Among four chloride salts, group 4 elements in catalysts TiCl₄ and ZrCl₄ ensured the same low yield of product 4 (8%) but differed in selectivity two-fold (44 and 81%, respectively). At the same time, SnCl₄ and ZnCl₂ afforded product 4 in three times higher yield (22%), but selectivity of SnCl₄ was much lower (57 vs. 81% for ZnCl₂). The poor performance of TiCl₄ and SnCl₄ can be explained by their hydrolysis with liberation of HCl under the reaction conditions. FeCl₃ was reported as an excellent catalyst for the synthesis of α-aminophosphonates from alkylphosphites,³⁹ but, in the case of triaryl phosphite 1, it was able to provide product 4 in only 15% yield with 68% selectivity.In addition, it was found that strong Lewis acids (e.g., TiCl₄ and BF₃) generate a large amount of a brown-black side product (polymer 12) formed by the removal of Boc protecting group and subsequent reaction of amine and aldehyde (Scheme 2).Less strong Lewis acids (e.g., Mg(OTf)₂ and LiOTf) generated significantly less polymer 12, however, most of aldehyde 2 was left unreacted providing poor conversion of the starting materials.An interesting comparison can be made between elements of group 3 – Y(OTf)₃ provided the highest yield (42%) and good selectivity (80%) of diaryl product 4, Sc(OTf)₃ showed similar selectivity (81%) but afforded much lower yield (16%) of product 4. Yb(OTf)₃ and La(OTf)₃ are located in the middle of Fig. 1, since they ensured formation of product 4 in 20 and 25% yield and with selectivity of 67 and 69%, respectively.The group of best-performing catalysts includes ZnCl₂, La(OTf)₃, Bi(OTf)₃, and Y(OTf)₃. On the scale of 3 g of target compound 4, the best performance was achieved with Y(OTf)₃, which provided the highest yield (42%), almost 4 times higher than in the case of Cu(OTf)₂ (11%). The stability of the paracetamol diester group was also one of the highest – only 20% of diester was hydrolyzed.This catalyst was used for elucidation of the behavior of aminal 7 in the reaction system. Y(OTf)₃-catalyzed reaction of aldehyde 2 and 2.0 equiv. of carbamate 3 after 2 h provided compound 7, which proved to be bench-stable and easily isolable. Aminal 7 was then reacted with tri(paracetamol) phosphite 1 under standard conditions in the presence of Y(OTf)₃. After 4 h, HPLC-UV assay with an internal standard showed only half amount of phosphonate 4 compared to that obtained in three-component Birum–Oleksyszyn reaction.According to these data, it can be concluded that aminal 7 can react with phosphite 1 but is twice less reactive than imine 6. Therefore, one-pot three-component reaction with in situ formation of imine is a preferable strategy for the synthesis of aryl α-aminophosphonates. Dehydrating agents like 4 Å MS and trimethyl orthoformate (TMOF) were not able to increase the yield over the standard protocol. A small increase in selectivity from 80% to 84% was noted when TMOF was used but with a much lower yield of 4 (17%).With the optimized conditions in hand, the efficiency of Y(OTf)₃ catalyst in the Birum–Oleksyszyn reaction was investigated using various aldehydes, carbamates, and aryl phosphites (Fig. 2). The highest yields of products were obtained for activated phosphites, for example, tris(p-methoxyphenyl) phosphite and the tris(p-acetamidophenyl) phosphite, combined with benzyl carbamate 3 and aromatic aldehydes (18, 22). The electron-donating substituent in phosphite facilitates the nucleophilic attack of phosphorus atom on the imine. Aliphatic aldehydes represented by t-butyl [4-(2-oxoethyl)phenyl]carbamate and 2-phenylacetaldehyde afforded lower yields (38–48%) of products (4, 29, 33) compared to the yields (72–92%) of products derived from benzaldehyde (14, 15, 17, 18). Among aromatic aldehydes, interesting results were obtained demonstrating how different halogen substituents in the para-position affect the yield of the respective product: 4-chlorobenzaldehyde (21) and 4-bromobenzaldehyde (26) provided higher yields (55 and 54%, respectively) compared to 4-fluorobenzaldehyde (20, 36%) and 4-iodobenzaldehyde (27, 25%). For product 27 the poor yield might be caused by its diminished solubility of starting aldehyde in MeCN. Compared to the standard conditions (application of AcOH) of Birum–Oleksyszyn reaction, the selected Lewis acid catalyst allows to perform the synthesis of α-aminophosphonates using acid-labile compounds, as demonstrated by the examples with t-butyl carbamate (34–36) and Boc-protected amine (4, 33). While yields of products 34 and 35 (43 and 41%, 34 and 35) were lower compared to those obtained for CbzNH₂ analogs (82 and 64%, 14 and 19), there were no elevated amounts of hydrolysis products. The lower conversion of starting materials might be explained by the higher steric hindrance of the tert-butyl group.¹⁸ Similarly, tri(o-tolyl)phosphite provided lower yields of products (34 and 26%, 16 and 25) when compared to the analogous reaction with triphenyl phosphite (82 and 55%, 14 and 21) and tri(p-tolyl)phosphite (75 and 43%, 15 and 24). These differences in yields also might be attributed to the increased steric hindrance near the phosphorus atom, which obstructs the nucleophilic attack of phosphite toward imine.Open in a separate windowFig. 2Scope of Birum–Oleksyszyn reaction catalyzed by Y(OTf)3 in anhydrous MeCN under argon. All the %yield presented is isolated yield.In general, the developed catalytic conditions using Y(OTf)₃ are well compatible with a variety of functional groups in both aldehyde and phosphite. When comparing series with benzaldehyde (15, 17, and 18) and 4-chlorobenzaldehyde (22, 23, and 24), the hydrolyzed side product was detected only in case of product 17 and 22 testifying the lower stability of the paracetamol ester.     

Optical and dielectric properties of NaCoPO4 in the three phases α, β and γ

In this work, we are interested in the synthesis of monophosphate α-NaCoPO₄, β-NaCoPO₄ and γ-NaCoPO₄ compounds by mechanochemical method and their characterization by X-ray powder diffraction patterns. These compounds are crystallized in the orthorhombic, hexagonal and monoclinic system, in Pnma, P6₅ and P2₁/n space groups, respectively. The optical properties were measured by means of the UV-vis absorption spectrometry in order to deduce the absorption coefficient α and optical band gap E_g. The calculated values of the indirect band gaps (E_gi) for three samples were estimated at 4.71 eV, 4.63 eV and 3.8 for compounds α, β and γ, respectively. The Tauc model was used to determine the optical gap energy of the synthesized compounds. Then, the results of the dielectric proprieties measured by varying the frequency are described.

In this work, we are interested in the synthesis of monophosphate α-NaCoPO₄, β-NaCoPO₄ and γ-NaCoPO₄ compounds by mechanochemical method and their characterization by X-ray powder diffraction patterns.     

Linear α-olefin production with Na-promoted Fe–Zn catalysts via Fischer–Tropsch synthesis

The production of linear alpha-olefins (α-olefins) is a practical way to increase the economic potential of the Fischer–Tropsch synthesis (FTS) because of their importance as chemical intermediates. Our study aimed to optimize Na-promoted Fe₁Zn_1.2O_x catalysts such that they selectively converted syngas to linear α-olefins via FTS at 340 °C and 2.0 MPa. The Fe₁Zn_1.2O_x catalysts were calcined at different temperatures from 350 to 700 °C before Na anchoring. The increase in the size of the ZnFe₂O₄ crystals comprising the catalyst had a negative effect on the reducibility of Fe oxides and the particle size of Fe₅C₂ during the reaction. The Na species in the catalyst restrained the reduction of Fe₁Zn_1.2O_x but facilitated the formation of Fe₅C₂. When pure Fe₁Zn_1.2O_x was calcined at 400 °C, the corresponding catalyst (i.e., Na_0.2/Fe₁Zn_1.2O_x (400)) exhibited higher catalytic activity and stability than the other catalysts for a 50 h reaction. Compared to the other catalysts, Na_0.2/Fe₁Zn_1.2O_x (400) enabled a higher number of active Fe carbides (Fe₅C₂) to intimately interact with the Na species, even though the catalyst had a lower total surface basicity based on surface area. The Na_0.2/Fe₁Zn_1.2O_x (400) showed a maximum hydrocarbon yield of 49.7% with a maximum olefin selectivity of 61.3% in the C1–C32 range. Examination of the reaction product mixture revealed that the Na_0.2/Fe₁Zn_1.2O_x catalysts converted α-olefins to branched paraffins (13.9–19.5%) via a series of isomerization, skeletal isomerization, and hydrogenation reactions. The Na_0.2/Fe₁Zn_1.2O_x (400) catalyst had a relatively low consumption rate of internal olefins compared to other catalysts, resulting in the lowest selectivity for branched paraffins. The Na_0.2/Fe₁Zn_1.2O_x (400) showed a maximum α-olefin yield (26.6%) in the range C2–C32, which was 27.9–50.0% higher than that of other catalysts. The α-olefin selectivity in the C5–C12 range for the Na_0.2/Fe₁Zn_1.2O_x (400) was 37.5% relative to the total α-olefins.

Intimate contact between Fe₅C₂ and Na₂O leads to high linear olefin selectivity with minimizing branched paraffin formation.     

Imbalance in α and β Globin Synthesis Associated with a Hemoglobinopathy

In contrast to findings in the thalasemia syndromes, studies of globin synthesis in subjects with structurally abnormal hemoglobins have generally revealed equal production of alpha and beta polypeptide chains. However, in the present investigation of globin biosynthesis in vitro in blood and marrow from two subjects heterozygous for unstable hemoglobin Leiden, beta6 or 7 Glu --> O, a significant excess of alpha-chain production was revealed. A mother and daughter of northern European ancestry with mild compensated hemolytic anemia were found to have 25% hemoglobin Leiden. Increased hemolysis occurred after the ingestion of a sulfonamide and during infections. Normal levels of hemoglobin A2, 3.0 and 2.7%, and hemoglobin F, 0.8 and 0.6%, were found in the two subjects. Similar percentages of the minor hemoglobins were demonstrated in other family members without hemoglobin Leiden. After incubation of peripheral blood with [(3)H]-leucine, the beta(A)/beta(Leiden) synthesis ratio was 1.3, and the specific activity of beta(Leiden) was 1.3-2 times beta(A). These results indicate preferential destruction of the unstable hemoglobin Leiden. However, in contrast to previous studies of other unstable hemoglobins, there was excess synthesis of alpha-chains. The total beta/alpha synthesis ratio was 0.47-0.63 in peripheral blood and 0.82 in marrow. A pool of free alpha-chains was demonstrated by starch gel electrophoresis and DEAE column chromatography. The synthesis of globin chains was balanced in family members without hemoglobin Leiden. This degree of predominance of alpha-chain synthesis in subjects with hemoglobin Leiden resembles the findings in heterozygous beta-thalassemia. However, the relatively normal hemoglobin content of the cells with this abnormal hemoglobin suggests the possibility of an absolute excess alpha-chain production in the hemoglobin Leiden syndrome.