STUDY MATERIAL FOR B.SC CHEMISTRY ORGANIC CHEMISTRY - II SEMESTER - III, ACADEMIC YEAR 2020-21
UNIT CONTENT PAGE Nr
II CARBOXYLIC ACIDS & ACID DERIVATIVES 07 ORGANOMETALLIC COMPOUNDS AND ORGANO III 17 SULPHUR COMPOUNDS IV REACTIVE METHYLENE COMPOUNDS & TAUTOMERISM 22
V ALICYCLIC COMPOUNDS 23
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UNIT - I ALDEHYDES AND KETONES The Carbonyl Group A carbonyl group is a chemically organic functional group composed of a carbon atom double-bonded to an oxygen atom --> [C=O] The simplest carbonyl groups are aldehydes and ketones usually attached to another carbon compound. These structures can be found in many aromatic compounds contributing to smell and taste.
Introduction Before going into anything in depth be sure to understand that the C=O entity itself is known as the "Carbonyl group" while the members of this group are called "carbonyl compounds" --> X-C=O. The carbon and oxygen are usually sp2 hybridized and planar.
Carbonyl Group Double Bonds The double bonds in alkenes and double bonds in carbonyl groups are very different in terms of reactivity. The C=C is less reactive due to C=O electronegativity attributed to the oxygen and its two lone pairs of electrons. One pair of the oxygen lone pairs are located in 2s while the other pair are in 2p orbital where its axis is directed perpendicular to the direction of the pi orbitals. The carbonyl groups properties are directly tied to its electronic structure as well as geometric positioning. For example, the electronegativity of oxygen also polarizes the pi bond allowing the single bonded substituent connected to become electron withdrawing.
Note: Both the pi bonds are in phase (top and botom blue ovals) The double bond lengths of a carbonyl group is about 1.2 angstroms and the strength is about 176-179 kcal/mol). It is possible to correlate the length of a carbonyl bond with its polarity; the longer the bond meaing the lower the polarity. For example, the bond length in C=O is larger in acetaldehyde than in formaldehyde (this of course takes into account the inductive effect of CH3 in the compound).
Knoevenagel reaction The Knoevenagel condensation is an organic reaction used to convert an aldehyde or ketone and an activated methylene to a substituted olefin using an amine base as a catalyst. The reaction begins by deprotonation of the activated methylene by the base to give a resonance stabilized enolate. The amine catalyst also reacts with the aldehyde or ketone to form an iminium ion intermediate, which then gets attacked by the enolate. The intermediate compound formed gets deprotonated by the base to give another enolate while the amine of the intermediate gets protonated. A rearrangement then ensures which releases the amine base, regenerates the catalyst, and yields the final olefin product An enol intermediate is formed initially:
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This enol reacts with the aldehyde, and the resulting aldol undergoes subsequent base-induced elimination:
A reasonable variation of the mechanism, in which piperidine acts as organocatalyst, involves the corresponding iminium intermediate as the acceptor:
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The Doebner-Modification in refluxing pyridine effects concerted decarboxylation and elimination:
Wolff-Kishner Reduction
The reduction of aldehydes and ketones to alkanes. Condensation of the carbonyl compound with hydrazine forms the hydrazone, and treatment with base induces the reduction of the carbon coupled with oxidation of the hydrazine to gaseous nitrogen, to yield the corresponding alkane. The Clemmensen Reduction can effect a similar conversion under strongly acidic conditions, and is useful if the starting material is base-labile.
Mechanism of the Wolff-Kishner Reduction
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Wittig reaction The Wittig reaction or Wittig olefination is a chemical reaction of an aldehyde or ketone with a triphenyl phosphoniumylide (often called a Wittig reagent) to give an alkene and triphenylphosphine oxide.
Mechanism of the Wittig reaction Following the initial carbon-carbon bond formation, two intermediates have been identified for the Wittig reaction, a dipolar charge-separated species called a betaine and a four-membered heterocyclic structure referred to as an oxaphosphatane. Cleavage of the oxaphosphatane to alkene and phosphine oxide products is exothermic and irreversible.
1) Nucleophillic attack on the carbonyl
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2) Formation of a 4 membered ring
3) Formation of the alkene
MEERWEIN-PONDORF-VERLEY REDUCTION - DEFINITION The reduction of ketones and aldehydes to their corresponding alcohols using Aluminium alkoxide catalyst in the presence of a sacrificial alcohol is called as Meerwein- Pondorf-Verley reaction.
Mechanism The MPV reduction is believed to go through a catalytic cycle involving a six-member ring transition state as shown in Figure 2. Starting with the aluminium alkoxide 1, a carbonyl oxygen is coordinated to achieve the tetra coordinated aluminium intermediate 2. Between intermediates 2 and 3 the hydride is transferred to the carbonyl from the alkoxy ligand via a pericyclic mechanism. At this point the new carbonyl dissociates and gives the tricoordinated aluminium species 4. Finally, an alcohol from solution displaces the newly reduced carbonyl to regenerate the catalyst 1.
Figure, Catalytic cycle of Meerwein–Ponndorf–Verley reduction
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UNIT - II CARBOXYLIC ACIDS & ACID DERIVATIVES Acid Strength The strength of the carboxylic acid (and any other Bronsted acid, for that matter), is related to the 'stability' of its conjugate base, the carboxylate anion. The carboxylic acid and the carboxylate anion are in equilibrium with one another, and the relative acidity of carboxylic acids depends upon the position of this equilibrium. One of the main reasons why carboxylic acids are acidic is due to the ability of the charge to be delocalised around the pi-system:
However, in addition to this delocalisation about the pi system, extra stability can be gained by the presence of electron withdrawing groups adjacent to the carboxylate group (i.e. -I groups attached to the R group in the diagram above). These electron withdrawing groups draw electron density away from the carboxylate anion via the sigma system (the single bonds). This is advantageous as the stability increases with the number of atoms it can be spread across (i.e. how diffuse the charge is). Electron releasing groups (+I as you call them) destabilise, by increasing the electron density around the carboxylate group, which of course makes it less favourable for the carboxylic acid to lose a proton and hence makes it less acidic. The +I groups aren't involved in breaking the O-H bond to any great extent, as you allude to. This is because when the proton leaves, it transfers its electron density to the oxygen it was attached to, cleaving the bond and allowing it to leave as H+. If the +I groups were donating into this bond, you would have to have the H leaving as H-, which is rarely observed.
Hell-Volhard-Zelinsky Reaction
Treatment with bromine and a catalytic amount of phosphorus leads to the selective α- bromination of carboxylic acids.
Mechanism of the Hell-Volhard-Zelinsky Reaction Phosphorus reacts with bromine to give phosphorus tribromide, and in the first step this converts the carboxylic acid into an acyl bromide.
An acyl bromide can readily exist in the enol form, and this tautomer is rapidly brominated at the α-carbon. The monobrominated compound is much less nucleophilic, so the
Page 7 of 28 STUDY MATERIAL FOR B.SC CHEMISTRY ORGANIC CHEMISTRY - II SEMESTER - III, ACADEMIC YEAR 2020-21 reaction stops at this stage. This acyl intermediate compound can undergo bromide exchange with unreacted carboxylic acid via the anhydride, which allows the catalytic cycle to continue until the conversion is complete.
Lactic Acid.
Lactic acid is the main constituent of milk that has gone sour and hence its name (L. Lactis=milk). Preparation. (1) By the hydrolysis of acetaldehyde cyanohydrin.
From Molasses. (2) Lactic acid is manufactured by fermentation of molasses (or milk whey containing lactose) by the microorganism Bacillus acidilactiti (BAL).
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A dilute solution of molasses (or whey) is treated with BAL (sour milk). The fermentation is carried at 35-40°C in the presence of CaCO3, As the lactic acid is produced, it reacts with CaCO3, to form calcium lactate. The calcium lactate is filtered off and decomposed with calculated quantity of dilute H2SO4. The insoluble Calcium sulphate is removed and the lactic acid set free in the solution is recovered by distillation in vacuo. The product is D-lactic acid.
Physical Properties. Lactic acid is a colourless, crystalline solid, mp 53°C, and has a sour taste. The acid obtained from molasses is D-isomer. The synthetic product is racemic lactic acid, mp 18°C, specific rotation [α] = +3.82, Lactic acid is soluble in water, alcohol, and ether.
Chemical Properties. Lactic acid molecule contains a secondary alcohol group (>CHOH) and a carboxyl group (COOH), and gives reactions of both.
Reaction Involving COOH Group. (1)Formtion of salt. It reacts with alkalis to form salts.
Reaction Involving OH Group.
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(2) Reaction with CH3COCl. The alcoholic OH group is acetylated on reaction with acetyl chloride in the presence of a base (pyridine).
(3) Reduction. When heated with Hl, it is reduced to propionic acid.
3+ (4) Oxidation. On oxidation with Fenton's reagent (H2O2/Fe ) it is converted to pyruvic acid. With KMnO4 it yields acetic acid.
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Reaction Involving Both OH And COOH. (5) Reaction with PCl5. Both the OH and COOH groups are attacked by phosphorus pentachloride to form lactyl chloride.
(6)Action of Heat. When heated alone, it forms an intermolecular cyclic diester called a Lactide.
(7) Reaction With H2SO4. When heated with dilute sulphuric acid at 130°C, lactic acid is decomposed to yield acetaldehyde and formic acid.
With concentrated H2SO4, formic acid is further decomposed to CO and H2O. (test)
Uses: Lactic acid is used. 1. in dairy products. 2. asacidulant in beverages and candies. 3. fordeliming of hides. 4. as a mordant. 5. Ethyl and butyl lactates are used as plasticisers. 6. Calcium and iron lactates are used in medicine.
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Urea.
It is the normal end product of the human metabolism of nitrogen-containing foods (proteins). An adult person excretes about 3 grams of urea in urine in 24 hours.
Preparation of urea (1) Urea is made commercially by the reaction of liquid ammonia and carbon dioxide at 150- 200°C and about 200 atmospheres pressure. Ammonium carbamate first formed decomposes to form urea.
(2) It can be prepared in the laboratory by the action of ammonia on carbonyl chloride.
(3) Wohler was the first to synthesise urea in 1828 by evaporating a solution of ammonium cyanate. This method is of historical interest only.
+ NH4 CNO H2N C NH2
Ammonium Cyanate Urea
Properties of Urea. Physical Properties. Urea is a colorless, crystalline solid, mp 135°C. It is very soluble in water giving neutral solutions. It is less soluble in alcohol and insoluble in ether, chloroform, and benzene.
Chemical Properties. Urea contains an amide group attached to an amino group and gives reactions of both these functions. It may be thought of as having two amide groups with a common - CO- function. Thus it behaves as a diamide in most reactions.
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Some of the reactions of urea are listed below. (1) Salt Formation: -14 Urea is a feeble mono acid-base (Kb= 1.5 x 10 ). Thus it reacts with concentrated nitric acid and oxalic acid to form salts.
+ The above salts contain the oxygen-protonated cation, [HOC(NH2)2] , which is resonance- stabilized.
(2) Hydrolysis: Like other amides, urea is hydrolysed under both acidic or alkaline conditions to give ammonia and carbon dioxide.
An enzyme called urease, present in soil and soya bean hydrolyzes urea to ammonium carbonate. This reaction is used for the quantitative estimation of urea.
(3) Reaction with HNO2: Urea, like other amides, reacts with nitrous acid when nitrogen is evolved, leaving the carbonic acid behind. This is turn decomposes to carbon dioxide and water.
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(4) Reaction with Alkaline Hypohalites: Urea is oidised to nitrogen when it is heated with excess of alkaline hypochlorite or hypobromite (Br2+NaOH).
This reaction is also used to estimate urea by measuring the volume of nitrogen envolved from a test sample.
(5) Acetylation: Urea reacts with acylating agents e.g., acetyl chloride to form N-acyl ureas or 'ureides'.
(6) Action of Heat (a) On heating at 132°C, urea melts. Then the liquid on gentle heating at a slightly higher temperature decomposes, liberating ammonia and leaving behind a solid compound known as Biuret.
Urea can be identified by the Biuret Test. The substance is heated, a little above its melting point, in a dry test-tube. Biuret is formed with the evolution of ammonia. When the evolution of ammonia begins to slacken, the residue is dissolved in water and treated with a few drops of sodium hydroxide solution. To the solution is then added a drop of copper sulfate solution, when a violet coloration is produced. (b) When heated quickly well above its melting point, urea is decomposed to isocyanic acid which trimerizes to cyanuric acid.
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(7) Reaction with Hydrazine: Urea reacts with hydrazine at 100°C to form semicarbazide.
Urea Structure. 1. By elemental analysis and molecular weight determination, its molecular formula has
been found to be CON2H4. 2. Diamide formula. Its formation from carbonyl chloride and ammonia indicates that urea has a symmetrical diamide formula.
The diamide formula is confirmed because of urea: (a) upon hydrolysis forms two molecules of ammonia
(b) with nitrous acid it liberates two molecules of N2.
(3) Facts against the Diamide formula: It fails to explain :
(a) Urea forms salts with acids like HCl or HNO3 while simple amides do not. (b) It forms mono-salts only e.g., CO(NH2)2. HCl, showing that the molecule is unsymmetrical.
(4) Tautomeric Structure Proposed:
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To explain the facts listed in (3), Chattaway proposed that urea exists as a tautomeric mixture.
It is the basic imide form which forms a salt with a monobasic acid at the imide group (= NH.HCI).
(5) Resonance Structures. Urea is more stable than could be expected of any carbonic acid derivative. In terms of the modern resonance theory, this stability of urea is attributed to its existence as a resonance hybrid.
(6) Formation of Mono-Salts Explained. The oxygen atom of the carbonyl group of urea is capable of coordinating with one proton (H+). The resulting cation is resonance stabilized by considerable delocalization of the cationic charge.
Thus urea can form mono-salt with an acid like HCl.
X-ray diffraction studies have confirmed that in the crystalline salt of urea with HCl is present an oxonium type cation as shown above.
H4N2O Uses (Urea) It is used as a nitrogen-release fertilizer It is used as a stabilizer in nitrocellulose explosives It is used in lanthanide chemistry as an important reagent It is used in the manufacturing of high explosive like urea nitrate It used in creams or ointments to rehydrate skin It is used in the urea breath test to detect the presence of bacteria in the stomach It is used as an ingredient in dish soap It is used in hair removal creams It is used in making pretzels as a browning agent It is used in the manufacture of melamine
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UNIT - III ORGANOMETALLIC COMPOUNDS AND ORGANO SULPHUR COMPOUNDS GRIGNARD REAGENTS Preparation Grignard reagents are prepared in the laboratory by the action of alkyl halides on magnesium metal in the presence of dry ether. R-X + Mg → R-Mg-X Alkyl halide Grignard reagent
Structure The role of ether here is not only to provide a medium for the function of GrignarD reagent but it also makes them dissolve (in ether) through solvolysis. If the function of ether is to dissolve the Grignard reagent by coordination of the type shown above, then it should be possible to prepare a Grignard reagent even in benzene in presence of a base like triethylamine. It has actually been found to be so. Only one mole of the base per mole of the alkyl halide is required. Grignard reagent in ether can exist EITHER in structure I or II. It has been pointed out recently that there is established an equilibrium between alkylmagnesiumhalide(Grignard reagent) and the corresponding dialkyl magnesium in ether solution as In right of the above fact, structure II seems to be more probable. Further, since the reaction of R2Mg in presence of MgX2 are the same as those of RMgX, it seems reasonable to represent Grignard reagent solvated in ether by the formulation I. 2RMgX↔ R2Mg + MgX2
SYNTHETIC USES 1. Preparation of hydrocarbon Compounds like water, alcohols, carboxylic acids and amines which contain active hydrogens react with Grignard reagents to produce hydrocarbons.
2. Preparation of alkene Grignard reagents react with reactive halides like benzyl chloride and allyl bromide to form alkanes and alkene respectively.
3. Preparation of alkynes The terminal alkynes react with Grignard reagents to produce alkylmagnesium halide which on subsequent treatment with alkyl halides undergo SN2 displacements to form higher alkynes.
4. Preparation of ethers Grignard reagents react with lower halogenated ethers to produce higher ethers.
5. Preparation of alkyl cyanides Alkyl cyanides are produced when Grignard reagents react with cyanogens and cyanogens chlorides.
6. Preparation of primary amine Grignard reagents react with chloroamines to give primary amines.
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7. Preparation of alkyl iodide When an alkyl magnesium chloride or bromide is treated with iodine, alkyl iodides are formed.
8. Preparation of 1°, 2°, 3° alcohols Grignard reagents react with aldehydes to produces alcohols. The reaction with formaldehydes gives primary alcohols, while with other aldehydes secondary alcohols are produced.
METHYL LITHIUM (CH3Li) Preparation: Organolithium compounds are obtained by the reaction of alkyl halides with metallic lithium in ether in an inert atmosphere of nitrogen or helium. CH3-Br + 2Li ( ,−10°, ₂ )→ CH3-Li + LiBr
PROPERTIES ℎ Physical properties Organolithium compounds are particularly sensitive towards air and moisture. These react with cyclic ethers, alkyl halides, active halogen compounds and carbonyl compounds much in the same fashion as do Grignard reagents.
Chemical properties Methyllithium is both strongly basic and highly nucleophilic due to the partial negative charge on carbon and is therefore particularly reactive towards electron acceptors and proton donors. In contrast to n-BuLi, MeLi reacts only very slowly with THF at room temperature, and solutions in ether are indefinitely stable. Water and alcohols react violently. Most reactions involving methyllithium are conducted below room temperature. Although MeLi can be used for deprotonations, n-butyllithium is more commonly employed since it is less expensive and more reactive.
Methyllithium is mainly used as the synthetic equivalent of the methyl anion synthon. For example, ketones react to give tertiary alcohols in a two-step process: Ph2CO + MeLi → Ph2C(Me)OLi + + Ph2C(Me)OLi + H → Ph2C(Me)OH + Li Nonmetal halides are converted to methyl compounds with methyllithium: PCl3 + 3 MeLi → PMe3 + 3 LiCl Such reactions more commonly employ the Grignard reagents methylmagnesium halides, which are often equally effective, and less expensive or more easily prepared in situ. It also reacts with carbon dioxide to give Lithium acetate: − + CH3Li + CO2 → CH3CO2 Li
Transition metal methyl compounds can be prepared by reaction of MeLi with metal halides. Especially important are the formation of organocopper compounds (Gilman reagents), of which the most useful is lithium dimethylcuprate. This reagent is widely used for nucleophilic substitutions of epoxides, alkyl halides and alkyl sulfonates, as well as for conjugate additions to α,β-unsaturated carbonyl compounds by methyl anion. Many other transition metal methyl compounds have been prepared. ZrCl4 + 6 MeLi → Li2ZrMe6 + 4 LiCl
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DIETHYL ZINC (C2H5)2 Zn Preparation Dialkylzincs are prepared by heating alkyl iodides with zinc in an atmosphere of CO2, and then distilling the product (alkylzinc iodide) in an inert atmosphere of CO2 . C2H5-I + Zn ( ₂) → C2H5-ZnI 2C2H5-ZnI ( 2 , ) → C2H5-Zn-C2H5 + ZnI2
Properties Dialkylzincs are colourless, unpleasant smelling liquids which have comparatively low boiling points. They are spontaneously inflammable in air and produce painful burns when brought into contact with skin. They give reaction similar to those of Grignard reagents but being difficult to handle are sparingly used in organic synthesis.
TETRA ETHYL LEAD Synthesis and properties TEL is produced by reacting chloroethane with a sodium–lead alloy. 4 NaPb + 4 CH 3CH2Cl → (CH3CH2)4Pb + 4 NaCl + 3 Pb
The product is recovered by steam distillation, leaving a sludge of lead and sodium chloride. TEL is a viscous colorless liquid. Because TEL is charge neutral and contains an exterior of alkyl groups, it is highly lipophilic and soluble in petrol (gasoline). Despite decades of research, no reactions were found to improve upon this rather difficult process that involves metallic sodium and converts only 25% of the lead to TEL. A related compound, tetramethyllead, was commercially produced by a different electrolytic reaction. A process with lithium was developed but never put into practice. Reactions
A noteworthy feature of TEL is the weakness of its four C–Pb bonds. At the temperatures found in internal combustion engines, (CH3CH2)4Pb decomposes completely into lead and lead oxides as well as combustible, short-lived ethyl radicals. Lead and lead oxide scavenge radical intermediates in combustion reactions. Engine knock is caused by a cool flame, an oscillating low-temperature combustion reaction that occurs before the proper, hot ignition. Lead quenches the pyrolysed radicals and thus kills the radical chain reaction that would sustain a cool flame, preventing it from disturbing the smooth ignition of the hot flame front. Lead itself is the reactive antiknock agent, and TEL serves as a gasoline-soluble lead carrier. When (CH3CH2)4Pb burns, it produces not only carbon dioxide and water, but also lead:
(CH3CH2)4Pb + 13 O2 → 8 CO2 + 10 H2O + Pb This lead can oxidize further to give species such as lead(II) oxide: 2 Pb + O2 → 2 PbO
Pb and PbO would quickly over-accumulate and destroy an engine. For this reason, the lead scavengers 1,2-dibromoethane and 1,2-dichloroethane are used in conjunction with TEL— these agents form volatile lead(II) bromide and lead(II) chloride, respectively, which are flushed from the engine and into the air.
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Reformatsky Reaction This reaction involves the interaction of an -bromoester with carbonyl compound (aldehyde and ketone) I presence of metallic zinc. An intermediate organo-zinc compound is first formed. This then adds on to the carbonyls group of aldehyde or ketone producing - hydroxyester. These can be readily dehydrated to , -unsaturated acids by heating with concentrated sulphuric acids.
THIOALCOHOLS The sulphur analogues of alcohols are called thioalcohols or thiols (thio=sulphur). They have the functional group –SH. Since thiols react with mercury oxide forming insoluble salts, they are commonly known as mercaptans (mercurius=mercury; captans=catching). Examples CH3SH Methyl mercaptan(methanethiol) CH3CH2SH Ethyl mercaptan (ethanethiol)
General methods of preparation 1. From alkyl halides Thiols may be prepared by heating an alkyl halide with an alcoholic solution of sodium or potassium hydrogen sulphide. C2H5Cl + KSH → C2H5SH + KCl Ethyl mercaptan 2. From alcohols Alcohols when heated with phosphorus pentasulphide from thioalcohols. 5C2H5OH + P2S5 → 5C2H5SH +P2O5 Ethanol Ethanethiol
General properties 1. Reaction with metals Thiols react with alkali metals like sodium, potassium etc to form mercaptides with the evolution of hydrogen. 2C2H5SH + 2Na → 2C2H5SNa + H2 Sodium ethyl mercaptide
2. Reaction with acids Thiols react with acids and acid chlorides to form thioesters CH3COOH + HSC2H5 → CH3COSC2H5 + H2O CH3COCl + HSC2H5 → CH3COSC2H5 + HCl Ethyl thioacetate
3. Reaction with aldehydes and ketones Thiols react with aldehydes and ketones in the presence of HCl to form mercaptals and mercaptols respectively.
4. Oxidation i). With mild oxidizing agents like H2O2, thiols are oxidized to disulphides. 2C2H5SH +H2O2→ C2H5-S-S-C2H5 + 2H2O ii). Strong oxidizing agents like HNO3 oxidise thiols to sulphonic acids. C2H5 SH +3(O) → C2H5 SO3H
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In organic chemistry, a methylene group is any part of a molecule that consists of two hydrogen atoms bound to a carbon atom, which is connected to the remainder of the molecule by two single bonds. The group may be represented as CH2<, where the '<' denotes the two bonds. This can equally well be represented as −CH2−. The hexamethylenediamine molecule contains six methylene groups.
This stands in contrast to a situation where the carbon atom is bound to the rest of the molecule by a double bond, which is preferably called a methylidene group, represented CH2=. Formerly the methylene name was used for both isomers. The name “methylene bridge“ can be used for the single-bonded isomer, to emphatically exclude methylidene. The distinction is often important, because the double bond is chemically different from two single bonds. The methylene group should be distinguished from the CH2 radical, which is a molecule unto itself, called methylidene or carbene. This was also formerly called methylene.
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UNIT – IV REACTIVE METHYLENE COMPOUNDS &TAUTOMERISM
Diethyl malonate Diethyl malonate, also known as DEM, is the diethyl ester of malonic acid. It occurs naturally in grapes and strawberries as a colourless liquid with an apple-like odour, and is used in perfumes. It is also used to synthesize other compounds such as barbiturates, artificial flavourings, vitamin B1, and vitamin B6.
Preparation Diethyl malonate may be prepared by reacting the sodium salt of chloroacetic acid with sodium cyanide, followed by base hydrolysis of the resultant nitrile to give the sodium salt malonicacid. Fischer esterification gives diethyl malonate:
Diethyl malonate synthesis
Reactions Like many other esters, this compound undergoes the Claisen ester condensations. The advantage of using this compound is that unwanted self-condensation reactions are avoided. Like other esters, this compound undergoes bromination at the alpha position.
Diethyl malonate can be nitrosated with excess sodium nitrite in acetic acid to afford diethyl oximinomalonate, catalytic hydrogenolysis of which in ethanol over Pd/C affords diethyl aminomalonate (DEAM). DEAM can be acetylated to produce diethyl acetamidomalonate (useful in amino-acid synthesis), or can be added with 3-substituted 2,4-diketones to boiling acetic acid to afford in maximal yield variously substituted ethyl pyrrole-2-carboxylates of interest for porphyrin synthesis.
Preparation Ethyl acetoacetate is produced industrially by treatment of diketene with ethanol. The preparation of ethyl acetoacetate is a classic laboratory procedure. It is prepared via the Claisen condensation of ethyl acetate. Two moles of ethyl acetate condense to form one mole each of ethyl acetoacetate and ethanol.
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UNIT - V ALICYCLIC COMPOUNDS
General methods of preparation (1) Freund’s method This method involves the action of zinc on suitable dihalides.
(2) From aromatic compounds-Six membered cyclo compounds can be easily obtained by the catalytic reduction of benzene and its derivatives.
Chemical properties The simple and the bigger cycloalkanes are very stable, like alkanes, and their reactions, for example, radical chain reactions, are like alkanes.
The small cycloalkanes – in particular, cyclopropane – have a lower stability due to Baeyer strain and ring strain. They react similarly to alkenes, though they do not react in electrophilic addition, but in nucleophilic aliphatic substitution. These reactions are ring- opening reactions or ring-cleavage reactions of alkyl cycloalkanes. Cycloalkanes can be formed in a Diels–Alder reaction followed by a catalytic hydrogenation. Medium rings exhibit larger rates in for example nucleophilic substitution reactions but smaller ones in ketone reduction. This is due to conversion from sp3 to sp2 states, or vice-versa, and the preference for sp2 state in medium rings, where some of the unfavourable torsional strain in saturated rings is relieved. Molecular mechanics calculations of strain energy differences SI between a sp2 and sp3 state show linear correlations with rates ( aslogk ) of many redox or substitution reactions.
Conformations and ring strain In cycloalkanes, the carbon atoms are sp3 hybridized, which would imply an ideal tetrahedral bond angle of 109° 28′′ whenev whenever possible. Owing to evident geometrical reasons, rings with 3, 4, and (to a very tiny extent) also 5 atoms can only afford narrower angles; the consequent deviation from the ideal tetrahedral bond angles causes an increase in potential energy and an overall destabilizing effect. Eclipsing of hydrogen atoms is an important destabilizing effect, as well. The strain energy of a cycloalkane is the theoretical increase in energy caused by the compound's geometry, and is calculated by comparing the
Page 23 of 28 STUDY MATERIAL FOR B.SC CHEMISTRY ORGANIC CHEMISTRY - II SEMESTER - III, ACADEMIC YEAR 2020-21 experimental standard enthalpy change of combustion of the cycloalkane with the value calculated using average bond energies. Conformations of cycloalkanes, their different strain contributions also with respect to reaction rates, and methods for their characterization are discussed briefly in the Wikipedia section Conformational isomerism. Molecular mechanics calculations are well suited to identify the many conformations occurring particularly in medium rings.Ring strain is highest for cyclopropane, in which the carbon atoms form a triangle and therefore have 60° C–C–C bond angles. There are also three pairs of eclipsed hydrogens. The ring strain is calculated to be around 120 kJ mol−1.
Cyclobutane has the carbon atoms in a puckered square with approximately 90° bond angles; "puckering" reduces the eclipsing interactions between hydrogen atoms. Its ring strain is therefore slightly less, at around 110 kJ mol−1.For a theoretical planar cyclopentane the C–C– C bond angles would be 108°, very close to the measure of the tetrahedral angle. Actual cyclopentane molecules are puckered, but this changes only the bond angles slightly so that angle strain is relatively small.
The eclipsing interactions are also reduced, leaving a ring strain of about 25 kJ mol−1.In cyclohexane the ring strain and eclipsing interactions are negligible because the puckering of the ring allows ideal tetrahedral bond angles to be achieved. As well, in the most stable chair form of cyclohexane, axial hydrogens on adjacent carbon atoms are pointed in opposite directions, virtually eliminating eclipsing strain.
After cyclohexane, the molecules are unable to take a structure with no ring strain, resulting in an increase in strain energy, which peaks at 9 carbons (around 50 kJ mol−1). After that, strain energy slowly decreases until 12 carbon atoms, where it drops significantly; at 14, another significant drop occurs and the strain is on a level comparable with 10 kJ mol−1. After 14 carbon atoms, sources disagree on what happens to ring strain, some indicating that it increases steadily, others saying that it disappears entirely. However, bond angle strain and eclipsing strain are an issue only for smaller rings.Ring strain can be considerably higher in bicyclic systems. For example, bicyclobutane, C4H6, is noted for being one of the most strained compounds that is isolatable on a large scale; its strain energy is estimated at 267 kJ mol−1
Baeyer’s strain theory : To compare stability of cycloalkanes BAEYER’S STRAIN THEORY
Baeyer’s strain theory When we carefully look over the cyclic saturated compounds, we find that each atom is sp3 hybridized. The ideal bond angle 109028’ but in cycloalkanes this angle is mathematically 180-(360/n) where n is the number of atoms making ring.
For example Cyclopropane, angle is 600; in Cyclobutane it is 900 and so on.
Page 24 of 28 STUDY MATERIAL FOR B.SC CHEMISTRY ORGANIC CHEMISTRY - II SEMESTER - III, ACADEMIC YEAR 2020-21
Angle Strain: This difference in ideal bond angle and real bond angle, is called angle strain and it causes strain in bond which affects the stability of molecule.
Greater is the deviation from the theoretical angle, greater is the Angle strain ; lesser the stability.
To calculate the distortion or angle strain in cycloalkane we assume the atoms of ring in a plane, such as in cyclopropane, all the 3 carbon atoms occupy one corner of an equilateral triangle with bond angle 60o. As two corners bent themselves to form bond so strain too is divided equally. So strain in cyclopropane will be ½ (109o28’ – 600) = 24044’.
Deviation of bond angle in cyclopropane from normal tetrahedral angle Distortion or strain = ½ (109028’ – bond angle of ring). So angle strains in some cycloalkanes are listed in the table below. Compound No. of C in the ring Angle between the C atoms Distortion n
Cyclopropane 3 600 24o44’
Cyclobutane 4 900 9o44’
Cyclopentane 5 108o 0o44’
Cyclohexane 6 120o -5o16’
Cycloheptane 7 128o34’ -9o33’
Cyclooctane 8 135o -12o62’
From the table it is clear that cyclopropane has the maximum distortion, so it is highly strained molecule and consequently more reactive than any of one monocylic alkanes, which is clear from the reaction that ring can be opened very easily to relieve strain on reaction with Br2, HBr or H2/Ni at high temperature.
In contrast, cyclopentane& cyclohexane have least strain so they are found more readily and are very stable as compared to cyclopropane.
Baeyer strain theory satisfactorily explains the typical reactivity and stability of smaller rings (from C3 to C5) i.e. Stability order follows : Cyclopropane But not valid for cyclohexane onwards because the strain again increases with the increase in number of carbon atom but actually large rings are more stable. So molecular orbital theory is also considered according to which covalent bond is formed by coaxial overlapping of atomic orbitals. The greater is the extent of overlap the stronger is the bond formed. In case of sp3 carbon, C – C bond will have maximum strength if the C-C-C bond have the angle 109o28’. If cyclopropane is an equilateral triangle then the bond angle of each C-C-C bond would be 60o. Therefore it was proposed by Couson that in cyclopropane the sp3 hybridized orbitals are not present exactly in one straight line due to mutual repulsion of orbital of these bonds Page 25 of 28 STUDY MATERIAL FOR B.SC CHEMISTRY ORGANIC CHEMISTRY - II SEMESTER - III, ACADEMIC YEAR 2020-21 resulting thereby loss of overlap. This loss of overlap weakens the bond and is responsible for its instability and strain in molecule. Similarly, in case of cyclobutane, there is also loss of overlap but the loss is less than in cyclopropane, so cyclobutane is more stable than cyclopropane. Overlapping of orbitals in large ring compound (5 more carbon atoms) is however much better which accounts for the greater stability of such compound. It is natural that when a molecule has strain within it, it will affect the stability of molecule. The stability of molecules can be calculated easily by measuring heat of combustion which will give the measure of total strain and thermochemical stability which can be calculated mathematically. Total strain = (No of C atom is the ring × observed heat of combustion/CH2) – observed heat of combustion/CH2 for n alkane. Experimental data of total strain for different cycloalkanes* Heat of combustion kJ per No. of C in the ring CH2group Total strain in kJ 3 697 115 4 686 109 5 664 27 6 659 0 7 662 27 8 663.8 42 9 664.6 54 From the data above it is clear that strain decreases from C3 to C6 i.e. stability increases, but stability again deteriorates from C7 to C9 ring system. According to this theory, the carbon atoms in 5 membered and smaller rings can lie in one plane as explained by Baeyer but Sachse suggested that in six membered and higher rings the carbon atoms are non planar . In this way the ideal angle 109028’ is retained and the ring is free from angle strain. ThusSachse proposed that cyclohexane exist in two puckered forms Page 26 of 28 STUDY MATERIAL FOR B.SC CHEMISTRY ORGANIC CHEMISTRY - II SEMESTER - III, ACADEMIC YEAR 2020-21 as boat and chair form. These forms are readily inter-convertible through half chair and twist boat forms simply by rotation about the single bonds. Muscone Muscone is an organic compound that is the primary contributor to the odour of musk. The chemical structure of muscone was first elucidated by LavoslavRužička. It consists of a 15- membered ring ketone with one methyl substituent in the 3-position. It is an oily liquid that is found naturally as the (−)-enantiomer, (R)-3-methylcyclopentadecanone. Muscone has been synthesized as the pure (−)-enantiomer as well as the racemate. It is very slightly soluble in water and miscible with alcohol. Natural muscone is obtained from musk, a glandular secretion of the musk deer, which has been used in perfumery and medicine for thousands of years. Since obtaining natural musk requires killing the endangered animal, nearly all muscone used in perfumery today is synthetic. It has the characteristic smell of being "Musky". One asymmetric synthesis of (−)-muscone begins with commercially available (+)- citronellal, and forms the 15-membered ring via ring-closing metathesis: A more Recent enantioselective synthesis involves an intramolecular aldol addition/dehydration reaction of a macrocyclic diketone.Muscone is now produced synthetically for use in perfumes and for scenting consumer products. Isotopologues of muscone have been used in a study of the mechanism of olfaction. Global replacement of all hydrogens in muscone was achieved by heating muscone with Rh/C in D2O at 150 °C. It was found that the human musk-recognizing receptor, OR5AN1, identified using a heterologous olfactory receptor expression system and robustly responding to muscone, fails to distinguish between muscone and the so-prepared isotopologue in vitro. OR5AN1 is reported to bind to muscone and related musks such as civetonethrough hydrogen-bond formation from tyrosine-258 along with hydrophobic interactions with surrounding aromatic residues in the receptor. Civetone Civetone is a macrocyclic ketone and the main odorous constituent of civet oil. It is a pheromone sourced from the African civet. It has a strong musky odor that becomes pleasant at extreme dilutions. Civetone is closely related to muscone, the principal odoriferous Page 27 of 28 STUDY MATERIAL FOR B.SC CHEMISTRY ORGANIC CHEMISTRY - II SEMESTER - III, ACADEMIC YEAR 2020-21 compound found in musk; the structure of both compounds was elucidated by Leopold Ružička. Today, civetone can be synthesized from precursor chemicals found in palm oil. Uses Civetone is used as a perfume fixative and flavor. In order to attract jaguars to camera traps, field biologists have used the cologne Calvin Klein's Obsession For Men. It is believed that the civetone in the cologne resembles a territorial marking Page 28 of 28