ZnCl2 catalyzed efficient synthesis of 1,3,4-oxadiazole and 1,3,4-thiadiazole

New methods for the synthesis of 1,3,4-oxadiazole and 1,3,4-thiadiazole have been described. No cyclizations took place in the absence of ZnCl₂. 1,3,4-Thiadiazoles are formed in the presence of ZnCl₂ alone, whereas oxadiazoles are produced when a base such as Et₃N or KOH was used along with ZnCl₂. % Yields are optimized.     

1,3,4-噁二唑和1,3,4-噻二唑衍生物的设计、合成和生物活性研究

为了寻求新型抗肿瘤药物,设计并合成了一系列新型1,3,4-噁二唑和1,3,4-噻二唑衍生物,对这些化合物在人类四种癌细胞:B-16(皮肤黑色素瘤细胞)、PC-3(人前列腺癌细胞)、U87(人原发性胶质母细胞瘤细胞)和A549(人非小细胞肺癌细胞)进行抗肿瘤活性评价.结果显示部分化合物具有较好的抗肿瘤活性,尤其是5-{6-[4-(2-羟基乙基)哌嗪-1-基]-2-甲基嘧啶-4-基氨基}-[1,3,4-噻二唑-2-羧酸(2-甲氧基苯基)酰胺(8b)]和5-{6-[4-(2-羟基乙基)哌嗪-1-基]-2-甲基嘧啶-4-基氨基}-[1,3,4-噻二唑-2-羧酸(4-甲氧基苯基)酰胺(8c)],对四种癌细胞都显示出较高的抗肿瘤活性,其抑制活性均优于阳性对照达沙替尼,随后对这类化合物抑制肿瘤的可能靶点开展了进一步研究.     

Low-temperature nematic phase in asymmetrical 1,3,4-oxadiazole bent-core liquid crystals possessing lateral methoxy group

Asymmetrical bent-core molecules based on 1,3,4-oxadiazole bent-core unit have been synthesised as a new design with a lateral methoxy group at outer phenyl ring of the molecule. These new asymmetrical bent-core molecules resemble hockey-stick shaped due to the presence of two different arms of different lengths. One arm of these molecules is elongated having two phenyl rings and possesses a 4-n-alkyloxy chain of a different number of carbon atoms (n = 4, 8, 12 and 18) and other arm is short and has one phenyl ring with fixed 4-n-octyloxy chain. The bent-core molecules possess a lateral polar methoxy group at the elongated arm of the molecule. These bent-core compounds exhibited fluorescence emission in the UV wavelength region (~377–386 nm) whereas in acetonitrile and dimethylformamide, solvent displays blue emission peak with a large stoke shift.The bent-core molecules with the number of carbon atoms (n = 4, 8 and 12) at the elongated arm exhibited monotropic nematic phase at low temperature, while the 4-n-octadecyloxy chain at the elongated arm displayed smectic A phase. Dielectric studies were performed in the nematic phase of the bent-core mesogens confirm the formation of the cybotactic cluster in the nematic mesophases.     

New Schiff's bases containing 1,3,4-thiadiazole and 1,3,4-oxadiazole units: a study of the effect of the heterocyclic ring and the position of the lateral alkoxy group on liquid crystalline properties

The synthesis of novel Schiff's bases incorporating the five-membered 1,3,4-thiadiazole (series 7, 9) and 1,3,4-oxadiazole (series 8, 10) rings have been prepared and their liquid crystalline properties studied. All compounds of series 7 exhibit an enantiotropic smectic C phase. No liquid crystalline properties were observed for the compounds of series 8-10. A study of the structure/mesomorphic activity relationship is also described.     

Spontaneous formation of chiral macrostructures in achiral hockey-stick liquid crystals

We report the synthesis and properties of a homologous series of asymmetrically substituted 4-(5-(4-benzyloxyphenyl)-1,3,4-oxadiazol-2-yl)phenyl 2-X-4-dodecyloxybenzoates, which have pronounced hockey-stick molecular architectures. The structure was varied through the lateral substitution with various groups, X (H, Me, MeO, Cl, F) in the outer benzene ring. The effect of the lateral group on liquid crystal phase behaviour was investigated by thermal optical microscopy and differential scanning calorimetry. Nematic and dark conclomerate phases were observed with both displaying macroscopically chiral domains.     

New Schiff's bases containing 1,3,4-thiadiazole and 1,3,4-oxadiazole units: a study of the effect of the heterocyclic ring and the position of the lateral alkoxy group on liquid crystalline properties

The synthesis of novel Schiff's bases incorporating the five-membered 1,3,4-thiadiazole (series 7, 9) and 1,3,4-oxadiazole (series 8, 10) rings have been prepared and their liquid crystalline properties studied. All compounds of series 7 exhibit an enantiotropic smectic C phase. No liquid crystalline properties were observed for the compounds of series 8-10. A study of the structure/mesomorphic activity relationship is also described.     

N-H?S hydrogen bonding in 2-mercapto-5-methyl-1,3,4-thiadiazole. Synthesis and crystal structures of mercapto functionalised 1,3,4-thiadiazoles

The synthesis and crystal structures of three mercapto functionalised 1,3,4-thiadiazoles and the crystal structure of 2-mercapto-5-methyl-1,3,4-thiadiazole are described. In the solid state, 2-mercapto-5-methyl-1,3,4-thiadiazole 1 forms a thioamide tautomer as shown by FTIR and Raman spectroscopy as well as X-ray crystallography and as theoretically predicted. The molecules are connected to form chains via N-H?S hydrogen bonds with N?S=328.3 pm. Bis(2-methyl-1,3,4-thiadiazolyl)-5,5′-disulfide 2, the disulfide of 1, as well as 2-(tert-butyldithio)-5-methyl-1,3,4-thiadiazole 3 and 2,5-bis(tert-butyldithio)-1,3,4-thiadiazole 4 have been synthesised and characterised by vibrational spectroscopy and X-ray diffraction.     

Structures of substituted di-aryl-1,3,4-oxadiazole derivatives: 2,5-bis(pyridyl)- and 2,5-bis(aminophenyl)-substitution

Crystal structures of four different di-aryl-1,3,4-oxadiazole compounds (aryl = 2-pyridyl-, 3-pyridyl-, 2-aminophenyl-, 3-aminophenyl-) are determined. Crystallization of di(2-pyridyl)-1,3,4-oxadiazole yielded monoclinic and triclinic polymorphs. The structures are characterized by the occurrence of π–π interactions. Additionally, in case of the aminophenyl compounds intra- as well as intermolecular hydrogen bonds are found that influence the packing motif as well. Since these molecules are often used as ligands in metal–organic complexes similarities and differences of the molecular conformation between the molecules in the pure crystals and that of the ligands in the complexes are discussed.     

五元杂环spacer结构调控的分子内电荷交互作用

研究五元杂环(spacer)桥对分子内电荷传递调控规律是开发功能分子材料的基础。本文通过环合反应制备了9个2,5-双二茂铁基五元杂环衍生物,包括: 2,5-双二茂铁基-1-苯基-吡咯(1),2,5-双二茂铁基呋喃(2),2,5-双二茂铁基噻吩(3),2,5-双二茂铁基-1H-咪唑(4),2,5-双二茂铁基噁唑(5),2,5-双二茂铁基噻唑(6),2,5-双二茂铁基-1H-1,3,4-三氮唑(7),2,5-双二茂铁基-1,3,4-噁二唑(8)和2,5-双二茂铁基-1,3,4-噻二唑(9)作为模型分子。通过元素分析,傅里叶变换红外(FTIR)光谱,质谱(MS)和核磁共振(NMR)等手段对化合物结构进行了表征,采用循环伏安电化学(CV)和密度泛函(DFT)量化模拟计算研究了分子内电荷传递与五元杂环(spacer)结构间的调控关系,发现化合物(1-9)二茂铁间电荷交互作用随着spacer中杂原子数量的增加而减小,分子内电荷选择短程杂原子桥作为传输通道,spacer结构对二茂铁间电荷传递发挥着重要的调控作用。     

Polyamides with pendant 1,3,4-oxadiazole and pyridine moieties

A novel aromatic diamine,2-（5-（3,5-diaminophenyl）-l,3,4-oxadiazole-2-yl）pyridine（POBD）,containing a pyridine ring and a 1,3,4-oxadiazole moiety,was synthesized.It was used in a polycondensation with various aromatic and aliphatic diacid chlorides to generate a series of new aromatic polyamides with pendant 1,3,4-oxadiazole groups.The prepared polyamides were characterized by IR,elemental analysis and through the synthesis of model compounds.Thermophysical properties of the synthesized polyamides have been studied by DSC,TGA and inherent viscosity measurements. Relatively high inherent viscosity values（0.76-1.62 dL/g,in 0.125%H₂SO₄ at 25℃） were observed for these compounds. Number average molecular weight（M_n） of the polymers was measured by vapor phase osmometry（VPO）.The introduction of bulky side chains in the structure of aromatic polyamides led to increased solubility of these polymers in common polar and aprotic solvents,such as DMF,DMSO,NMP and DMAc,which allowed thin films to be cast from polymer solutions. The highest molecular weight（M_n = 51190） was observed for polymer（DC）,which was prepared from pyridine-2,6-dichlorocarbonyl.     

Synthesis and biological activity of 1,3,4-oxa(thia)diazole, 1,2,4-triazole-5-(thio)one and S-substituted derivatives of 3-((2-carboxyethyl)phenylamino)propanoic acid

Research on Chemical Intermediates - A series of novel derivatives of 3-((2-carboxyethyl)phenylamino)propanoic acid bearing two identical substituted 1,3,4-oxadiazole, 1,3,4-thiadiazole, or...     

Synthesis,Reactions, and Anticancer Activity of Some 1,3,4-Thiadiazole/Thiadiazine Derivatives of Carbazole

A novel method for the synthesis of 1,3,4-thiadiazole and 1,3,4-thiadiazine derivatives bearing a carbazole moiety is described. Carbazole was transformed into carbazole-9-thiocarbohydrazide in two steps. This compound was allowed to react with various electrophiles to yield 1,3,4-thiadiazole derivatives. The reaction with bifunctional electrophiles led to 1,3,4-thiadiazines. 2-(Carbazol-9-yl)-5,6-dihydro-4H-1,3,4-thiadiazin-5-one reacted with piperidine and formaldehyde to yield the 4-(piperidin-1-ylmethyl) derivative. The reaction with aromatic aldehydes led to the corresponding 6-arylidene derivatives, which were transformed into pyrimidino[4,5-e]-1,3,4-thiadiazines and pyrazolo[3,4-e]-1,3,4-thiadiazines by a reaction with guanidine, acetamidine, or phenylhydrazine, respectively. Structures of the products were confirmed by ¹H NMR, ¹³C NMR, IR, and mass spectrometric measurements. Selected examples of products were screened for anticancer activity.     

Poly(1,3,4-oxadiazole-ether-imide)s and their polydimethylsiloxane-containing copolymers

Poly(1,3,4-oxadiazole-ether-imide)s were prepared by thermal imidization of poly(amic-acid) intermediates resulting from the solution polycondensation reaction of a bis(ether-anhydride), namely 2,2′-bis-[(3,4-dicarboxyphenoxy)phenyl]-1,4-phenylenediisopropylidene dianhydride, with different aromatic diamines containing 1,3,4-oxadiazole ring, such as 2,5-bis(p-aminophenyl)-1,3,4-oxadiazole, 2,5-bis[p-(4-aminophenoxy)phenyl]-1,3,4-oxadiazole, 2-(4-dimethylaminophenyl)-5-(3,5-diaminophenyl)-1,3,4-oxadiazole. Poly(1,3,4-oxadiazole-ether-imide)-polydimethylsiloxane copolymers were prepared by polycondensation reaction of the same bis(ether-anhydride) with equimolar quantities of an aromatic diamine having 1,3,4-oxadiazole ring and a bis(aminopropyl)polydimethylsiloxane oligomer of controlled molecular weight. A solution imidization procedure was used to convert quantitatively the poly(amic-acid) intermediates to the corresponding polyimides. All the polymers were easily soluble in polar organic solvents such as N-methylpyrrolidone and N,N-dimethylacetamide. The polymers showed good thermal stability with decomposition temperature being above 400 °C. Solutions of some polymers in N-methylpyrrolidone exhibited blue fluorescence, having maximum emission wavelength in the range of 370-412 nm.     

Synthesis and characterisation of asymmetrical mesogenic materials based on 2,5-disubstituted-1,3,4-oxadiazole

New mesogenic homologous series bearing 1,3,4-oxadiazole ring with a nitro terminal group, 4-(5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl)phenyl 4-((4-methoxybenzylidene)amino)benzoate (G₁–G₁₁), were synthesised. Their chemical structures are identified by fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (¹H-NMR) and elemental analysis. The liquid crystalline properties of the series G_n and their precursory F_n were screened by differential scanning calorimetry and optical polarising microscopy (OPM). The compounds of the series G_n were screened by thermogravimetric analysis to observe their thermal stability. The target compounds (G_n) in this study, were displayed different liquid crystalline mesophase, the first two homologous (G₁ and G₂) did not show any liquid crystalline behaviour, the homologous (G₃–G₁₀) which have an alkoxy terminal group (n = 3–10) exhibited nematic phase, whilst the last derivative of the series (G₁₁), n = 12, displayed SmA phase. The mesomorphic properties of these derivatives were affected by the presence of the nitro group at the end of the molecules which was classified as a strong polar group. Also, the role of alkoxy terminal chain and the bent heterocyclic ring (1,3,4-oxadiazole) in the liquid crystalline properties of these molecules were debated.     

Synthesis and in vitro antibacterial activity of new oxoethylthio-1,3,4-oxadiazole derivatives

In the present investigation, a series of 2(4-pyridyl)-5[(aryl/heteroarylamino)-1-oxoethyl]thio-1,3,4-oxadiazole were synthesized using isonicotinohydrazide and substituted aryl/heteroaryl amines using pyridine as solvent. Newly synthesized compounds were tested for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv using the BACTEC 460 radiometric system. Among the synthesized compounds, compounds 2(4-pyridyl)-5((2-nitrophenylamino)-1-oxoethyl)thio-1,3,4-oxadiazole (5e), 2(4-pyridyl)-5((4-nitrophenylamino)-1-oxoethyl)thio-1,3,4-oxadiazole (5g) and 2(4-pyridyl)-5((2-pyrrolylamino)-1-oxoethyl)thio-1,3,4-oxadiazole (5k) produced highest efficacy and exhibited >90% inhibition at a concentration of 0.0077, 0.0052 and 0.0089 μM, respectively. All the new compounds were pharmacologically evaluated for their in vitro Antimicrobial activity.     

Synthesis,characterisation and mesomorphic behaviours of non-symmetrically substituted 1,2,4- and 1,3,4-oxadiazole derivatives

Two series of non-symmetrically substituted bent-core mesogens derived from the central 3,5 and 2,5 cores of the 1,2,4- and 1,3,4-oxadiazole derivatives, respectively, containing ether and ester linkage have been synthesised by several straightforward synthetic procedures, and their mesomorphic behaviour was studied by optical polarising microscopy (OPM) and differential scanning calorimetry (DSC). The last five homologues of the 1,2,4-oxadiazole series exhibit a monotropic nematic phase on cooling, while the 1,3,4-oxadiazole derivatives do not show any liquid crystalline properties but rather a crystal to isotropic transition is observed by OPM. We show that the bent angles of the 1,2,4- and 1,3,4-oxadiazole rings are crucial in observing the liquid crystal (LC) phases formed, and also that the length of the alkyl substituent is observed to have a significant effect on the nature of the LC phases.     

Solid-Phase Synthesis of 2-Arylamino-5-(4-hydroxyphenyl)-1,3,4-thiadiazole Derivatives Based on Resin-Bound Acylhydrazines

A highly efficient, solid-phase synthesis of 2-arylamino-5-(4-hydroxy-phenyl)-1,3,4-thiadiazole derivatives under mild conditions has been developed. The 1,3,4-thiadiazole derivatives were synthesized from resin-bound acylhydrazines in several steps, which gave 78–88% overall yields and excellent purities of the products.     

Synthesis of 1,2,4-Triazol-3-ylmethyl-, 1,3,4-Oxa-, and -Thiadiazol-2-ylmethyl-1<Emphasis Type="Italic">H</Emphasis>-[1,2,3]-triazolo[4,5-<Emphasis Type="Italic">d</Emphasis>]pyrimidinediones

Summary. 1-Carbethoxymethyl-4,6-dimethyl-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5,7(4H,6H)-dione was synthesized and treated with hydrazine hydrate to give the corresponding hydrazide. The latter hydrazide was treated either with phenylisothiocyanate or with carbon disulfide/alc. KOH to afford the corresponding thiosemicarbazide and oxadiazole derivatives. Alkylation of 2-mercapto-1,3,4-oxadiazole with dimethyl sulfate or ethyl chloroacetate gave the corresponding 2-methylthio-, and 2-ethylthioglycolate derivatives. Formation of 1,3,4-thiadiazole, 5-mercapto-1,2,4-triazole, and 1,3,4-oxadiazole were carried out by treating of the latter thiosemicarbazide with conc. H₂SO₄, NaOH/HCl, and HgO. Treating of 5-mercapto-1,2,4-triazole with ethyl chloroacetate afforded the thioglycolate ester. Hydrolysis of the latter with hydrazine hydrate afforded the hydrazide derivatives. Condensation of these hydrazides with monosaccharide aldoses gave the corresponding sugar hydrazones. The novel compounds were tested for antiviral activity against hepatitis B virus and showed moderate activities.     

Synthesis and antitumor activity of novel pyridazinone derivatives containing 1,3,4-thiadiazole moiety

Abstract

A series of novel pyridazinone derivatives containing the 1,3,4-thiadiazole moiety were synthesized and characterized by ¹H NMR, 13C NMR, spectroscopies HRMS and IR. Among them, the structure of compound 5c (2-(Tert-butyl)?4-chloro-5-((5-((2-ethylphenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One) was unambiguously confirmed via single crystal X-ray diffraction analysis. The inhibitory activity of all the target compounds against MGC-803 and Bcap-37 was determined by MTT assay, with doxorubicin (the inhibition rates were 95.5?±?0.4% and 95.7?±?1.0% respectively) as a control. The preliminary results showed that the inhibitory activity of compound 5n (2-(Tert-butyl)?4-chloro-5-((5-((3-fluorophenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One) was superior to the others. The inhibition rates of MGC-803 and Bcap-37 cells were 86.3?±?2.2% and 92.3?±?0.6% at a concentration of 10?μmol/L, respectively. The preliminary structure-activity relationship showed that when the 2-position of the benzene ring was substituted by a methyl group, such as compound 5j (2-(Tert-butyl)?4-chloro-5-((5-((2,3-dimethylphenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), it exhibited good anticancer activity on MGC-803 cells. Besides, introducing fluorine, chlorine, or trifluoromethyl group onto the benzene ring, such as compound 5?m (2-(Tert-butyl)?4-chloro-5-((5-((4-(trifluoromethoxy)phenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), displayed good anticancer activity on MGC-803 and Bcap-37 cells.     

2,5-二苯腙基-1,3,4-噻二唑类化合物的合成及抗腐蚀性能研究

以2,5-二巯基-1,3,4-噻二唑为原料, 与水合肼反应制得2,5-二肼基-1,3,4-噻二唑, 再将其与取代苯甲醛缩合, 得到了6种新的2,5-二苯腙基-1,3,4-噻二唑类化合物, 其结构经元素分析、红外、¹H NMR及质谱等方法所证实. 6种噻二唑衍生物对喷气燃料银片腐蚀有一定的抑制作用.