Imidazole

Discovery


Imidazole was first synthesized by Heinrich Debus in 1858, but various imidazole derivatives had been discovered as early as the 1840s. His synthesis, as shown below, used glyoxal and formaldehyde in ammonia to form imidazole. This synthesis, while producing relatively low yields, is still used for creating C-substituted imidazoles.


In one microwave modification the reactants are benzil, formaldehyde and ammonia in glacial acetic acid forming 2,4,5-triphenylimidazole (Lophine).
australian opal ring


Structure and properties
tiffany mesh ring


Imidazole is a 5-membered planar ring, which is soluble in water and other polar solvents. It exists in two equivalent tautomeric forms because the hydrogen atom can be located on either of the two nitrogen atoms. Imidazole is a highly polar compound, as evidenced by a calculated dipole of 3.61D, and is entirely soluble in water. The compound is classified as aromatic due to the presence of a sextet of -electrons, consisting of a pair of electrons from the protonated nitrogen atom and one from each of the remaining four atoms of the ring.


Some resonance structures of imidazole are shown below:


Amphotericity


Imidazole is amphoteric, i.e. it can function as both an acid and as a base. As an acid, the pKa of imidazole is 14.5, making it less acidic than carboxylic acids, phenols, and imides, but slightly more acidic than alcohols. The acidic proton is located on N-1. As a base, the pKa of the conjugate acid (cited above as pKBH+ to avoid confusion between the two) is approximately 7, making imidazole approximately sixty times more basic than pyridine. The basic site is N-3.


Preparation


A ball-and-stick model of imidazole, showing carbon-carbon and a carbon-nitrogen double bonds.


Imidazole can be synthesized by numerous methods besides the Debus method. Many of these syntheses can also be applied to different substituted imidazoles and imidazole derivatives simply by varying the functional groups on the reactants. In literature, these methods are commonly categorized by which and how many bonds form to make the imidazole rings. For example, the Debus method forms the (1,2), (3,4), and (1,5) bonds in imidazole, using each reactant as a fragment of the ring, and thus this method would be a three-bond-forming synthesis. A small sampling of these methods is presented below.


Formation of one bond


The (1,5) or (3,4) bond can be formed by the reaction of an imidate and an -aminoaldehyde or -aminoacetal, resulting in the cyclization of an amidine to imidazole. The example below applies to imidazole when R=R1=Hydrogen.


Formation of Two Bonds


The (1,2) and (2,3) bonds can be formed by treating a 1,2-diaminoalkane, at high temperatures, with an alcohol, aldehyde, or carboxylic acid. A dehydrogenating catalyst, such as platinum on alumina, is required.


The (1,2) and (3,4) bonds can also be formed from N-substituted -aminoketones and formamide and heat. The product will be a 1,4-disubstituted imidazole, but here since R=R1=Hydrogen, imidazole itself is the product. The yield of this reaction is moderate, but it seems to be the most effective method of making the 1,4 substitution.


Formation of Four Bonds


This is a general method which is able to give good yields for substituted imidazoles. It is essentially an adaptation of the Debus method called the Debus-Radziszewski imidazole synthesis. The starting materials are substituted glyoxal, aldehyde, amine, and ammonia or an ammonium salt.


Formation from other Heterocycles


Imidazole can be synthesized by the photolysis of 1-vinyltetrazole. This reaction will only give substantial yields if the 1-vinyltetrazole is made efficiently from an organotin compound such as 2-tributylstannyltetrazole. The reaction, shown below, produces imidazole when R=R1=R2=Hydrogen.


Imidazole can also be formed in a vapor phase reaction. The reaction occurs with formamide, ethylenediamine, and hydrogen over platinum on alumina, and it must take place between 340 and 480 C. This forms a very pure imidazole product.


Biological significance and applications


Imidazole is incorporated into many important biological molecules. The most pervasive is the amino acid histidine, which has an imidazole side chain. Histidine is present in many proteins and enzymes and plays a vital part in the structure and binding functions of hemoglobin. Histidine can be decarboxylated to histamine, which is also a common biological compound. It is a component of the toxin that causes urticaria, which is another name for allergic hives. The relationship between histidine and histamine are shown below:


One of the applications of imidazole is in the purification of His-tagged proteins in immobilised metal affinity chromatography(IMAC). Imidazole is used to elute tagged proteins bound to Ni ions attached to the surface of beads in the chromatography column. An excess of imidazole is passed through the column, which displaces the His-tag from nickel co-ordination, freeing the His-tagged proteins.


Imidazole has become an important part of many pharmaceuticals. Synthetic imidazoles are present in many fungicides and antifungal, antiprotozoal, and antihypertensive medications. Imidazole is part of the theophylline molecule, found in tea leaves and coffee beans, which stimulates the central nervous system. It is present in the anticancer medication mercaptopurine, which combats leukemia by interfering with DNA activities.


Pharmaceutical derivatives


The substituted imidazole derivatives are valuable in treatment of many systemic fungal infections.


Ketoconazole


Miconazole


Fluconazole


Itraconazole


Voriconazole


Industrial applications


Imidazole has been used extensively as a corrosion inhibitor on certain transition metals, such as copper. Preventing copper corrosion is important, especially in aqueous systems, where the conductivity of the copper decreases due to corrosion.


Many compounds of industrial and technological importance contain imidazole derivatives. The thermostable polybenzimidazole PBI contains imidazole fused to a benzene ring and linked to a benzene, and acts as a fire retardant. Imidazole can also be found in various compounds which are used for photography and electronics.


Salts of imidazole


Salts of imidazole where the imidazole ring is in the cation are known as imidazolium salts (for example, imidazolium chloride). These salts are formed from the protonation or substitution at nitrogen of imidazole. These salts have been used as ionic liquids and precursors to stable carbenes. Salts where a deprotonated imidazole is an anion are also possible; these salts are known as imidazolide salts (for example, sodium imidazolide).


Related heterocycles


Benzimidazole, an analog with a fused benzene ring.


Dihydroimidazole or benzimidazoline, an analog where 4,5-double bond is saturated.


Pyrrole, an analog with only one nitrogen atom in position 1.


Oxazole, an analog with the nitrogen atom in position 1 replaced by oxygen.


Thiazole, an analog with the nitrogen atom in position 1 replaced by sulfur.


Pyrazole, an analog with two adjacent nitrogen atoms.


References


^ Alan R. Katritzky; Rees. Comprehensive Heterocyclic Chemistry. Vol. 5, p.469-498, (1984).


^ Grimmett, M. Ross. Imidazole and Benzimidazole Synthesis. Academic Press, (1997).


^ Brown, E.G. Ring Nitrogen and Key Biomolecules. Kluwer Academic Press, (1998).


^ Pozharskii, A.F, et al. Heterocycles in Life and Society. John Wiley & Sons, (1997).


^ Heterocyclic Chemistry TL Gilchrist, The Bath press 1985 ISBN 0-582-01421-2


^ Heinrich Debus (1858). "Ueber die Einwirkung des Ammoniaks auf Glyoxal". Annalen der Chemie und Pharmacie 107 (2): 199 208. doi:10.1002/jlac.18581070209. 


^ Microwave-Mediated Synthesis of Lophine: Developing a Mechanism To Explain a Product Crouch, R. David; Howard, Jessica L.; Zile, Jennifer L.; Barker, Kathryn H. J. Chem. Educ. 2006 83 1658


^ US6,177,575 (PDF version) (2001-01-23) A. J. Arduengo, Process for Manufacture of Imidazoles. 


^ Comprehensive Pharmacy Review, Leon Shargel, 6th edition, p930.


v  d  e


Antifungals (D01 and J02)


Wall/


membrane


Ergosterol


inhibitors


Azoles


(lanosterol 14


alpha-demethylase inhibitors)


Imidazoles


topical: Bifonazole, Clomidazole, Clotrimazole#, Croconazole, Econazole, Fenticonazole, Ketoconazole, Isoconazole, Miconazole#, Neticonazole, Oxiconazole, Sertaconazole, Sulconazole, Tioconazole


Triazoles


topical: (Fluconazole#, Fosfluconazole)


systemic: (Fluconazole, Itraconazole, Posaconazole, Voriconazole)


Benzimidazoles


topical: Thiabendazole


Polyene antimycotics


(ergosterol binding)


topical: (Natamycin, Nystatin#)


systemic: (Amphotericin B#)


Allylamines


(squalene monooxygenase


inhibitors)


topical: (Amorolfine, Butenafine, Naftifine, Terbinafine)


systemic: (Terbinafine)


-glucan synthase


inhibitors


echinocandins (Anidulafungin, Caspofungin, Micafungin)


Intracellular


Pyrimidine analogues/


Thymidylate synthase inhibitors


Flucytosine#


Mitotic inhibitors


Griseofulvin#


Others


Bromochlorosalicylanilide  Methylrosaniline  Tribromometacresol  Undecylenic acid  Polynoxylin  Chlorophetanol  Chlorphenesin  Ticlatone  Sulbentine  Ethyl hydroxybenzoate  Haloprogin  Salicylic acid  Selenium sulfide#  Ciclopirox  Amorolfine  Dimazole  Tolnaftate  Tolciclate  Sodium thiosulfate#  Whitfield's ointment#  Potassium iodide#


Tea tree oil citronella oil lemon grass orange oil patchouli lemon myrtle


PCP: Pentamidine Dapsone Atovaquone


#WHO-EM. Withdrawn from market. CLINICAL TRIALS: hase III. Never to phase III


see also diseases


Categories: Imidazoles | AlkaloidsHidden categories: Chemboxes which contain changes to watched fields

Six types of noise standards for small household electrical appliances will be formally released

Frbiz Site





Day was August 1, 2005 the formal implementation of the mandatory national standard GB19606-2004 "Household and similar electrical noise limits" Series Adds New "D", air purifier, dishwasher, vacuum vacuum cleaners and water suction cleaning appliances, electric kitchen appliances, food blenders,


Humidifier
men's spandex shorts


This Category 6
men's thong underwear


Small appliances


Noise limits the special requirements of products currently in the WTO / TBT online publicity and will shortly be released.





"Electrical" press to see the 6 products of the noise limits specified in the special requirements of the Draft for Approval, standard all the technical content is mandatory. 6 products in the nameplate or instruction manual for the specific noise level must be marked, and the measured value and the deviation between the values expressed should not exceed 3dB (A), and the maximum should not exceed the standard limit value. Director of the National Standardization Technical Committee appliances Lee said that enterprises should pay more attention to this set of criteria, as a national mandatory standards, once the formal implementation of the 6 categories of products related to business and business should be strictly according to laws and regulations, in a timely manner express the noise value products.





"Household and similar electrical appliances Particular requirements for humidifiers noise limit," Draft for Approval provides that: "humidifier noise sound power level shall comply with requirements." "Household and similar electrical appliances noise limit of food blenders special requirements "applicable to rated voltage 220V, rated power not exceeding 700W, household and similar purposes by the motor-driven high-speed rotating blade inside the container to stir or crush food blenders, rated power 700W or more appliances are being considered . The noise limit requirements include immersion of solid food blenders and food blenders noise value of two types of products required. Provides food blenders immersion noise limits are: power 400W apparatus noise value can not exceed 90dB (A), 400W <power 700W apparatus noise value can not exceed 90dB (A); and solid food blenders noise limit value: 400W power apparatus noise can not exceed 100dB (A), 400W <power 700W apparatus noise can not exceed 105dB (A).





"Household and similar electrical noise limits for the special requirements of electric kitchen appliances," also applies to motor rated less than 700W input power apparatus, power requirements of 700W or more devices are also being considered. According to Lee describes, the standards applicable to devices other than the Food and shredding electric kitchen appliances, such as


Soymilk


,


Juicer


And so on. The standard provides specific noise limits.





"Household and similar electrical appliances noise limit of vacuum cleaners and water suction cleaning appliances for special requirements," provision, which applies only to domestic and similar use of vacuum cleaners and water suction cleaning appliances (including its accessories and components parts ). Noise limit requirements for products: vacuum cleaners rated input power 1000W, the noise limit values should be 84dB (A); Rated input power> 1000W and 1400W, the noise limit value is 86dB (A); Rated input power > 1400W, the noise limit value is 90dB (A). Water suction cleaning appliances noise value should be no greater than 90dB (A).





"Household and similar electrical appliances Particular requirements for dishwashers noise limit" and "Household and similar electrical noise limits for the special requirements of the air purifier" on the products were also made noise limit provisions. Of these, air purifier noise sound power level should be consistent with the provisions of Table 3. The dishwasher in the sound power level of vertical noise limit values Otherwise than 61dB (A), desktop dishwasher is not greater than 65dB

Cherub with Chariot Egg

Frbiz Site


Design


The exact design of the Cherub with Chariot Egg is unknown and there is no known drawing or photograph of the egg. There is a brief description from the imperial records in the Russian State Historical Archives in Moscow which describes the gift as "Angel pulling chariot with egg - 1500 roubles, angel with a clock in a gold egg 600 roubles." According to Marina Lopato in Faberg: Imperial Jeweller (1993) this description means the clock is inside the gold egg, which is in the chariot being pulled by the angel. Faberg's invoice carries a similar description, itemizing a cherub pulling a chariot with an egg and a cherub with clock in a gold egg. These two descriptions are backed up by the 1917 inventory of seized imperial treasure which reads "gold egg, decorated with brilliants (diamonds), a sapphire; with a silver, golded [sic] stand in the form of a two-wheeled wagon with a putto."


Surprise
chime alarm clock


The surprise would have been the clock being inside the egg on the chariot, though the exact design is not known.
pig charms


History of the egg


The egg would have been presented to Maria Feodorovna on April 24th, 1888 by Alexander III. The egg was kept in the Gatchina Palace in 1891, and was one of 40 or so eggs sent to the Armory Palace of the Kremlin in 1917 after the Revolution by the Provisional Government. In 1922 it was transferred to the Sovnarkom, after which the exact whereabouts of the egg are unknown. In the 1930's Victor and Armand Hammer may have purchased the egg. A sales catalog for Armand Hammer's 1934 exhibition at Lord and Taylor in New York describes a "miniature silver armour holding wheelbarrow with Easter Egg, made by Faberg, court jeweler" which seems to describe the Cherub with Chariot Egg. Armand Hammer may have been unaware of the significance of this item if it was in fact the 1888 Imperial egg, since he had a habit of promoting imperial items yet did not make an effort to promote this egg. Whether this was the 1888 egg, and where it is today is unknown.


See also


Egg decorating


Notes


^ Lowes, Will; McCanless, Christel Ludewig (2001). Faberg Eggs A Retrospective Encyclopedia. Lanham, Maryland: Scarecrow Press Inc.. p. 24. ISBN 0-8108-3946-6. 


^ Lowes, 2001 Pg. 24


^ Lowes, 2001 Pg. 25


^ Lowes, 2001 pg. 25


^ Lowes, 2001 pg. 25


v  d  e


Faberg Eggs


Imperial Easter Eggs


Hen  Hen with Sapphire Pendant  Blue Serpent Clock  Cherub with Chariot  Ncessaire  Danish Palaces  Memory of Azov  Diamond Trellis  Caucasus  Renaissance  Rosebud  Twelve Monograms  Rock Crystal  Alexander III Portraits  Coronation  Mauve  Lilies-of-the-Valley  Pelican   Bouquet of Lilies Clock  Pansy   Trans-Siberian Railway  Cockerel   Basket of Wild Flowers  Gatchina Palace  Clover Leaf  Empire Nephrite  Peter the Great  Royal Danish  Moscow Kremlin  Swan  Rose Trellis  Cradle with Garlands  Alexander Palace  Peacock   Standart Yacht  Alexander III Commemorative  Colonnade  Alexander III Equestrian  Fifteenth Anniversary  Bay Tree  Tsarevich  Napoleonic  Romanov Tercentenary  Winter  Mosaic  Grisaille   Red Cross with Triptych   Red Cross with Imperial Portraits  Steel Military  Order of St. George  Karelian Birch  Constellation (unfinished)


Faberg Kelch Eggs


Twelve Panel  Pine Cone  Apple Blossom  Rocaille  Bonbonnire  Chanticleer


Other Faberg eggs


Blue Striped Enamel   Duchess of Marlborough  Rothschild  Youssoupov  Nobel Ice  Resurrection  Spring Flowers


Categories: Lost Faberg eggs | 1888 works

Hebei Jingxing built up the largest chemical base of calcium and magnesium

Frbiz Site





    Hebei Province Jingxing full advantage of local resources, and continuously upgraded to mention the promotion of calcium and magnesium industry, and created a three highest in the country, namely, calcium and magnesium in the country's largest annual output, the national minimum product cost, product variety of the whole garden the most complete, now become the largest chemical base of calcium and magnesium.



electrolysis of water


    Jingxing limestone, dolomite reserves of 13.3 billion tons, the production of calcium and magnesium products, excellent raw material. Built in 1974, the first since the calcium carbonate plant, calcium and magnesium in the county to 90 more than the rapid development of enterprises, but there is a small-scale enterprises, backward technology and equipment, products, low-grade issues. In order to promote the development of calcium and magnesium industries across the county in accordance with "great loss" development principles, and actively guide the enterprises to adopt merger, custodian, joint-stock reform and other means to accelerate the development of large enterprise groups.
specimen container





Among them, calcium factory in northern China two companies combined to form the North China Calcium Industry Co., Ltd., annual output reach 8.5 million tons, becoming the country's largest manufacturer of light calcium; Chunlan chemical companies to lease and managed approach to the three Ca factory implementation of the merger, annual production of over 4 thousand tons. At present, calcium and magnesium in the county more than 100 million tons of annual production, accounting for one-third of the national market share.





    To further enhance the market competitiveness of calcium and magnesium, the county has invested nearly 5,000 million, to accelerate the pace of business technology innovation of traditional coal-fired, choice of materials, drying, carbonation tower and a series of manufacturing process equipment for the rehabilitation and upgrading, so that tons of coal consumption from 200 kg down to 100 kilograms of product, production increased by 50%, tons of product cost lower than the national average cost of more than 100 yuan. At the same time, the county through the crosswise union, grafting techniques and other measures to vigorously develop hi-tech projects.





Factory activity in the development of magnesium hydroxide calcium of new products, price of an ordinary light calcium 3 times. Taihang investment of 8 million yuan to build, and Tsinghua University are jointly developing nano-calcium project. Calcium and magnesium products is currently the county has in the past a single common development of the activity of calcium and magnesium calcium, medical calcium, paper calcium, magnesium carbonate, etc. more than 10 varieties, the product market from the rubber, paint industry, to expand into the medical, food, plastics, paper, PVC pipe and many other fields, has been initially built the country's largest chemical base of calcium and magnesium.