Friday, March 13, 2015

SEMESTER – VI Organic Chemistry - II 2.3. UNIT – II Pharmaceuticals

SEMESTER – VI
Organic Chemistry - II
2.3.            UNIT – II  Pharmaceuticals- Explanation with two examples each for

              An analgesic, or painkiller, is any member of the group of drugs used to achieve analgesia — relief from pain, without blocking the conduction of nerve impulses, markedly altering sensory perception, or affecting consciousness. Analgesics may be classified into two types: anti-inflammatory drugs, which alleviate pain by reducing local inflammatory response and the opioids, which act on the brain
(Eg) Acetaminophen, Anacin, Avinca, Cozet, Comphunox

Antibacterial: Anything that destroys bacteria or suppresses their growth or their ability to reproduce. Heat, chemicals such as chlorine, and antibiotic drugs all have antibacterial properties.
(Eg)  Amoxicillin, ampicillin, cefazolin, cefataxime, penicillin G, rifabutin, sulphanomides, cephalosporins, tetracyclin, trimethoprim, erythromycin

Antibiotics, also known as antibacterials, are types of medications that destroy or slow down the growth of bacteria. The Greek word anti means "against", and the Greek word bios means "life" (bacteria are life forms).
(Eg)  Amoxicillin, ampicillin, cefazolin, cefataxime, penicillin G, rifabutin, sulphanomides, cephalosporins, tetracyclin, trimethoprim, erythromycin.
Antiviral: An agent that kills a virus or that suppresses its ability to replicate and, hence, inhibits its capability to multiply and reproduce. Antiviral drugs are one class of antifungal and anti parasitic drugs.
(Eg) Amantadine, oseltamivir, zanamir.
Antipyretics are substances that reduce fever.
(Eg) acetaminophen, adalimumab, allopurinol, amitriptyline.
Antituberculosis -drugs are medicines used to treat tuberculosis, an infectious disease that can affect the lungsand other organs.
(Eg)  cycloserine (Seromycin), ethambutol (Myambutol),ethionamide (TrecatorSC), isoniazid (Nydrazid, Laniazid),pyrazinamide, rifabutin (Mycobutin), and rifampin (Rifadin,Rimactane).
Antitussive - any medicine used to suppress or relieve coughing.
(Eg) codeine, hydro codeine, butophanol
Anti allergic is a hyper sensitivity disorder of the immune system. Symptoms include red eyes,itchinessand runny nose, eczema,hives or an asthma attack.
(Eg) antihistamines,glucocartiaoids,epinephrine,theophylline.
Antidiabetes  - drugs used in diabetes to lowering glucose level in blood.
(Eg) alpha glucosidase inhibitors,amylin analogue,sulfonylureas,metformin,meglitinides,thiazolidinediones.
Tranquilizers- drugs that is used to reduce anxiety,fear,tension,agitation and related state of mental disturbance. They are classified in to two classes namely major and minor.
(Eg) phenothiazine,thioxanthiazines,butyrophenones,benzodiazepines,diazepam,meprobamate.
Antiseptic and disinfectant - Antiseptics are antimicrobial substances that are applied toliving tissue or skin to reduce the possibility of infection,sepsisor putrefaction.
     Disinfectants destroy micro organisms found on non living objects.
(Eg) tincture iodine,hydrogen peroxide,peracetic acid,povidone-iodine,
Antimalarial- drugs used to treat or prevent malaria.
(Eg) 4-aminoquinolines,chloroquinone,amodiaquine,quinine and quinidine.
Anaesthetics ( local  and general) an anaesthetic is a drug that causes anaesthesia which is a reversible loss of sensation .
Local anasthetics- procaine ,amethocaine,cocaine,iodocaine,prilocaine.

General  anasthetics- amytal,brevital,surital,penthothal

Thursday, February 26, 2015

Organometallic Compounds and Catalysis

Organometallic chemistry is the chemistry of compounds which contain a metal carbon 
bond. A catalyst is defined as a substance that 
accelerates the rate of achieving chemical equilibrium,and which can berecovered unchanged at
the end of a reaction. Catalytic processes can be broadly defined into two categories: 1) 
homogeneous catalysis, a process where the catalysts and reactants remain in the same phase; 
and 2) heterogeneous catalysis, where the reactants and catalysts are in different phases. In most 
heterogeneous catalytic systems the catalyst is in the solid phase and the reactants are liquids or
gases,the homogeneous organometallic catalyst , RhCl(PPh3)3, which catalyzes the hydrogenation of olefins.

Wilkinson fully explored the scope, selectivity, andmechanismby which the complex 
catalyzes the hydrogenation of olefins and the compound is now commonly referred to as 
“Wilkinson’s catalyst.” The major mechanistic features of the reaction sequence can be shown 
by using what is known as a catalytic cycle ora Tolman loop, Figure 1.Wilkinson’s catalyst is not a catalystbut, rather a catalyst precursor! The actual catalyst is 
believed to be the solvento complex, (S)RhCl(PPH3)2. The problemof identifying the true active 
catalyst in catalytic systems is exceedingly difficult. Only through detailed mechanistic studies 
can an experimentalist gain any certainty of the active catalyst. There exist many reports in the 
scientific literature of‘catalysts’ which in reality are not catalysts at all. Often impurities or 
decomposition products catalyze the reactions of interest. 


In the catalytic cycle there are several important steps central to many organometallic reaction mechanisms.  A key example is the reaction of dihydrogen with the solvento complex to form a cis-dihydride species:

RhCl(P(C6H5)3)2(S) + H2  cis - RhCl(P(C6H5)3)2(S)(H)2
                                           A                                                             B

This reaction is known as an oxidative-addition reaction.  Note that in this chemical transformation, A is bound to only four ligands while B is bound to six.  We call species A a four-coordinate “coordinately unsaturated” compound and B is “coordinately saturated”.  Note also that species A is a Rh(I) complex with 16 total valence electrons and species B is a Rh(III) complex with 18 valence electrons.  Thus in an oxidative-addition reaction the coordination number of the metal changes from four to six and the oxidation state of the metal increases by two.  The reverse of an oxidative-addition reaction is also common and is termed a reductiveelimination reaction.

 A.    Synthesis and Characterization of Wilkinson’s Catalyst.

RhCl3 . 3 H2O  +  P(C6H5)3    RhCl(P(C6H5)3)3

Place 5 mL of absolute ethanol in a round-bottom flask equipped with a magnetic stirring bar. Attach a water condenser and place the apparatus in a sand bath on a stirrer hot plate.  Heat the ethanol to just below its boiling point (78 oC).  Remove the condenser momentarily, add 150 mg of triphenylphosphine to the hot ethanol and stir until the solid is dissolved.  A small amount of solid may remain at this point.  Remove the condenser once again, add 25 mg of hydrated rhodium(III) chloride to the solution and continue to stir.  Heat the solution to a gentle reflux for ~ 30 minutes.  Bright shiny burgundy-red crystals should form during this time.  Collect the product crystals by suction filtration on a Hirsch funnel while the solution is hot.  Wash the crystals with three 1-mL portions of ether.  Dry the crystals on the filter by continuous suction. Calculate the percentage yield and determine the melting point of the product.  Obtain the IR spectrum and the 1H NMR spectrum of the compound.  Save the product in a labeled vial.

B.     Absorption of Hydrogen by Wilkinson’s Catalyst.

RhCl(P(C6H5)3)3  +  H2    RhCl(P(C6H5)3)2H2

Place 25 mg of RhCl(PPh3)3 and a stir bar in a small flask fitted with a septum and a needle outlet.  Purge the apparatus with N2 (rubber tubing and a needle) for 5 minutes.  Add 3 mL of chloroform to a different flask and bubble with H2 for 10 minutes.  Using a syringe, add the chloroform to the RhCl(PPh3)3 with stirring.  Allow the reaction to proceed for 5 minutes.  Concentrate the solution under the flow of H2 gas.  When the solution is sufficiently concentrated (~0.2 mL) add deoxygenated ether dropwise until precipitation occurs.  Cool the flask in an ice water bath and collect the light yellow crystals by suction filtration using a Hirsch funnel.



METALLOCENES

Introduction

    a metallocene

    The cyclopentadienyl (Cp) ligand is a monoanionic ligand with the formula C5H5. The first characterized example of a cyclopentadienyl complex was ferrocene, Cp2Fe, which has an iron atom "sandwiched" between two planar Cp rings as shown on the left. For this reason, bis(cyclopentadienyl) complexes are sometimes called "sandwich compounds" ormetallocenes. Some metallocene derivatives, such as Cp2TiCl2, have their Cp rings tilted with respect to each other and are called "bent metallocenes", while complexes with only one Cp ligand have been colorfully described as having "half sandwich" and "3-legged piano stool" geometries.

    Bonding in Cp Complexes

      The normal bonding mode for Cp is eta5 (pentahapto), for which several different resonance structures can be drawn for the bonding of an eta5-Cp ligand to a transition metal complex. The one on the right makes it easy to remember that a Cp ligand donates either 5 or 6 electrons to a transition metal complex (depending on which electron counting formalism you use) as it looks like one alkyl ligand + two alkene ligands:
      some resonance forms
      While some of these forms are important in special cases (see ring slips below), a molecular orbital (MO) diagram best describes the bonding in a Cp complex. Consider the five MO's of a Cp ligand. If we have two of these, we can add and subtract various orbital combinations to generate the MO diagram for a metallocene.

    Cp orbitals
      The lowest energy orbital, a1, does not have any favorable overlap with any of the metal d-orbitals. It has little interaction with the dz2 because the ligand p-orbitals lie on the dz2 conical nodal plane. The e1g set of degenerate orbitals overlaps quite well with the dxz and dyz orbitals on the metal, forming a strong set of pi-bonds. The e1u interaction between the metal px and py also gives some stabilization. Although the metal dx2-y2 and dxy can overlap with the e2g orbitals on the ligand, the degree of overlap is not very large and these levels are essentially non-bonding.
      The MO diagram for generic metallocenes, Cp2M is shown below. Notice that the Cp orbitals fill the six lowest orbitals. The next five unoccupied MO's shown in the box have little or no bonding character, which explains our observation above that metallocenes are known for a variety of d-electron counts.

    an MO diagram
      As one can infer from the MO description, most Cp complexes display completely delocalized bonding with equivalent C-C bond lengths in the C5 ring. The carbon-carbon bond distance of 143.3(6) pm in the Cp ring of ferrocene is somewhat longer than that observed in Na(TMEDA)Cp ( C-C distance of 138 pm) and other aromatic systems such as benzene (C-C distance = 135 pm). The longer C-C distance in ferrocene is the result of pi-backbonding from filled d-orbitals on Fe to the antibonding molecular orbitals on Cp.
      While the C5 ring of ferrocene is planar, the hydrogens are bent downwards towards the metal by about 5 degrees. This can be ascribed to a canting of the p-orbitals on carbon which permits better overlap of the ligand MO's with the metal orbitals (see the MO diagram below).
      The success of Cp ligands in contemporary organotransition metal chemistry can be traced to several key features:

      • The M-Cp bond dissociation is large (ferrocene is stable to 400 degrees C).
      • The ligand tends not to get involved chemically (although it certainly can from time to time).
      • The ligand blocks several coordination sites.
      • It has excellent NMR properties

Sunday, February 8, 2015

UNIT - IV Carbon pi-donor complexes

Rajah Serfoji Govt. College (Autonomous), Thanjavur – 613 005

            M.Sc., Chemistry – CBCS Pattern           SEMESTER – II
Inorganic Chemistry - II                                                                     Code: R2PCHEL2

UNIT  - IV                         Carbon  pi-donor  complexes 

HYDROGENATION OF ALKENES
The double bond of an alkene consists of a sigma (σ) bond and a pi (Ï€) bond. Because the carbon-carbon Ï€ bond is relatively weak, it is quite reactive and can be easily broken and reagents can be added to carbon. Reagents are added through the formation of single bonds to carbon in an addition reaction.
Introduction
An example of an alkene addition reaction is a process called hydrogenation.In a hydrogenation reaction, two hydrogen atoms are added across the double bond of an alkene, resulting in a saturated alkane. Hydrogenation of a double bond is a thermodynamically favorable reaction because it forms a more stable (lower energy) product. In other words, the energy of the product is lower than the energy of the reactant; thus it is exothermic (heat is released). The heat released is called the heat of hydrogenation, which is an indicator of a molecule's stability Although the hydrogenation of an alkene is a thermodynamically favorable reaction, it will not proceed without the addition of a catalyst 
Common catalysts used are insoluble metals such as palladium in the form Pd-C, platinum in the form PtO2, and nickel in the form Ra-Ni. With the presence of a metal catalyst, the H-H bond in H2 cleaves, and each hydrogen attaches to the metal catalyst surface, forming metal-hydrogen bonds. The metal catalyst also absorbs the alkene onto its surface. A hydrogen atom is then transferred to the alkene, forming a new C-H bond.  A second hydrogen atom is transferred forming another C-H bond. At this point, two hydrogens have added to the carbons across the double bond.  Because of the physical arrangement of the alkene and the hydrogens on a flat metal catalyst surface, the two hydrogens must add to the same face of the double bond, displaying syn addition.















Common Applications
Hydrogenation reactions are extensively used to create commercial goods.Hydrogenation is used in the food industry to make a large variety of manufactured goods, like spreads and shortenings, from liquid oils. This process also increases the chemical stability of products and yields semi-solid products like margarine. Hydrogenation is also used in coal processing. Solid coal is converted to a liquid through the addition of hydrogen. Liquefying coal makes it available to be used as fuel.

Hydroformylation, also known as oxo synthesis or oxo process, is an important homogeneously catalysed industrial process for the production of aldehydes from alkenes. This chemical reaction entails the addition of a formyl group (CHO) and a hydrogen atom to a carbon-carbon double bond.  Hydroformylation is also used in specialty chemicals relevant to the organic synthesis of fragrances and natural products. The development of hydroformylation, which originated within the German coal-based industry, is considered one of the premier achievements of 20th-century industrial chemistry
The process typically entails treatment of an alkene with high pressures (between 10 to 100 atm) of carbon monoxide and hydrogen at temperatures between 40 and 200 °C. Transition metal catalysts are required.

The original catalyst was HCo(CO)4.


 A generic rhodium catalyst, where PAr3 = triphenylphosphineor its sulfonated analogue Tppts. Seetris(triphenylphosphine)rhodium carbonyl hydride.
The overall mechanism resembles that for homogeneous hydrogenation with additional steps. The reaction begins with the generation of coordinatively unsaturated metal hydrido carbonyl complex such as HCo(CO)3 and HRh(CO)(PPh3)3. Such species bind alkenes, and the resulting complex undergoes amigratory insertion reaction to form an alkyl complex.
A key consideration of hydroformylation is the "normal" vs. "iso" selectivity. For example, the hydroformylation ofpropylene can afford two isomeric products, butyraldehyde or isobutyraldehyde:
H2 + CO + CH3CH=CH2 → CH3CH2CH2CHO ("normal")
vs.
H2 + CO + CH3CH=CH2 → (CH3)2CHCHO ("iso")
These isomers result from the differing ways of inserting the alkene into the M–H bond. Of course, both products are not equally desirable. Much research was dedicated to the quest for catalyst that favored the normal isomer.
When the hydrogen is transferred to the carbon bearing the most as tributyl phosphine), then this steric effect is greater. Hence, the mixed carbonyl/phosphine complexes offer a greater selectivity toward the straight chain products.



Olefin Complexes (I): Zeise's Salt
Zeise's salt, the first p-complex ever obtained was made in 1827 by the Danish Chemist Zeise who boiled a mixture of KCl and PtCl4 in ethanol. Today, the compound is obtained in somewhat higher yield by bubbling ethylene through a solution of K2PtCl4.Zeise's Salt was also the first organometallic compound ever published.




Olefin Complexes (II): The Chatt-Duncanson Model
 
The now generally accepted description of the bonding situation in olefin complexes was given by Chatt and Duncanson.
By measuring the IR-spectrum of Zeise's salt, Chatt and Duncanson recognized that the CC-bond of ethylene in Zeise's salt still possesses double bond character but to a lesser degree than free ethylene. The CC-stretching frequency was lower than that of free ethylene.The metal donates electrons to the antibonding p*-orbital of the olefin thus reducing the bond order and accordingly, the CC stretching frequency.

Olefin p-complexes can also be conveniently described with two mesomeric structures:

With increasing strength of the olefin-metal interaction, the metal-carbon bond distance will decrease and the CC-bond distances will increase. If this geometric distortion is strong enough, it is legitimate to describe the olefin-complex as metalla-cyclopropane. It is possible to estimate the strength of the metal-olefin interaction from structural data. More convenient is the analysis of the IR-spectrum.
 The strength of the metal-olefin interaction depends on the olefin's   substituents as well. Electron withdrawing substituents (-CN, F etc.) favor complexation and the cyclopropane structure.
An entirely different type of olefin complex was obtained by Norton in 1982:


Olefin Complexes (III): Synthesis
Olefins act as two electron donors and can replace other to electron donors in metal complexes. These processes are often thermodynamically unfavorable and require activation of the complex.
This is typically done my transforming an 18 VE complex into an 16 VE complex. With very few exceptions, 16 VE complexes react spontaneously with olefins to give h2-olefin complexes.
Especially reactive are cationic 16 VE complexes:

The replacement of CO ligands in carbonyl complexes usually requires photochemical activation, but dienes like 1,3-butadiene or norbornadiene can react thermally:

Olefin complexes are usually more reactive than carbonyl complexes and are valuable starting materials for organometallic research. In favorable cases, homoleptic olefin complexes can be stable. The complex Ni(COD)2 is commercially available. The best synthesis uses NiCl2 as starting material, triethylaluminum as reducing agent and butadiene as stabilizer.



Butadiene prevents the precipitation of metallic nickel by forming a labile olefin complex and becomes subsequently replaced with COD.The exchange of CO for olefins is usually thermodynamically unfavorable. Nevertheless, the reaction often occurs readily because any CO formed can rapidly escape from the reaction solution into the gas phase.
The reactivity of the olefin also plays a significant role. Particularly reactive is norbornadiene:


More often, the more basic nitriles are used to obtain the labile nitrile complexes first:



The use if propionitrile instead of the more readily available acetonitrile allows higher reaction temperatures and reduced reaction times (a few h for propionitrile, many days for acetonitrile.

Allyl Complexes
The first allyl-complex was obtained 1959 by Smidt and Hafner.The allyl group can coordinate to transition metal fragments in as h1- or 3-ligand:


The allyl ligand can be counted as cation (2e-donor), anion (4e-donor) or as radical (3e-donor).
Depending on the nature of the metal and other co-ligands, allyl-complexes can behave as electrophilic or nucleophilic allyl-synthons (sources of allyl+ or allyl-).
The bonding situation in p-Allylcomplexes can be described by MO theory.