MANNICH REACTION

Mannich reaction gives keto amines by reacting enolisable Carbonyl compound with formaldehyde and secondary amine. 

It introduces dialkyl amino methyl group at alpha position of enolisable carbonyl compounds.

It involves condensation of enolisable Carbonyl compound with iminium ion.

Enolisable carbonyl compound + HCHO + secondary amine =  keto amine

First we will talk about "Aldol reaction '' of enolisable aldehydes and ketones with formaldehyde. The biggest problem here is Formaldehyde-- Too reactive, really this is the problem. So, will see the product when acetaldehyde (enolisable) reacts with formaldehyde in presence of mild base.

Now we will see one conversion, the product is unsaturated ketone ( product of aldol condensation)

OK, shall we proceed via ''aldol condensation with formaldehyde" or ''Mannich'' reaction to get the above unsaturated ketone?

               Vote goes to ''Mannich reaction'' ( Problem with formaldehyde so far we discussed.

                                                    NOW MANNICH REACTION

In the Mannich reaction imine salt forms from secondary amine and formaldehyde. The resulting imine salt attacks on enolisable aldehydes or ketones. By using Mannich reaction we can add only one molecule of HCHO to ketone or aldehyde.

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ZAISTAV vs HOFMANN ELIMINATION

zaistav elimination:

Normal elimination of alkyl halides (attacking of a base(nucleophile) on hydrogen instead of carbon) lead to form more substituted alkene as major product (Zaistav elimination product). The elimination proceeds by E1 or E2 mechanism.

Hofmann elimination:

Amines on exhaustive methylayion gives Quaternary ammonium salts which on treatment with moist silver oxide and on heating eliminates tertiary amine and forms less substituted alkene as the major product ( contrary to Zaistav product)

Explanation:

• For the Elimination(E2) of ''H'' and ''tertiary amine'' from quaternary ammonium salt , both should be anti-peri planar arrangement.
• In the Newmann projection to form more substituted alkene( Zaistav product) there is " Gauche interaction", which cause less stability. Hence less substituted alkene is the minor product.

• In the Newmann projection to form less substituted alkene (Hofmann product) there is no Gauche interaction between tertiary amine and hydrogen which is relatively more stable and E2 elimination leads to form Hofmann elimination product

QUALITATIVE ORGANIC ANALYSIS

We will discuss the analysis of elements (C,N,O,S,X,P) present in an organic compound.

1. Detection of carbon and Hydrogen:

2. Detection of N,S and Halogen:

Lassaigne test

: Fuse the organic compound with Na , which converts covalently bonded N,S and X present in organic compound to water soluble NaCN, Na2S and NaX. If organic compound contain both ''N'' and "S'', then converts to NaSCN, which reduced by excess Na to give NaCN and Na2S.

(a) Detection of Nitrogen:

• Take the sodium fusion mixture and add equal volume of FeSO4 and then boil the mixture. Cool the mixture and add few drops of H2SO4. Formation of Prussian blue conforms the presence of Nitrogen.

Note: 1) Diazo compounds donot give Lassaigne tese because they loose N2 gas even at moderate temperature.

2) Hydrazine (NH2NH2) also donot give the test since it does not contain "C''.

3) Some nitrogen compounds like amides on heating with sodalime gives NH3 [ NH3 tests: adding Nesslers reagent]

(b) Detection of sulphur:

• Take sodium fusion extract and add sodium nitroprusside, violet colour indicates the presence of "sulphur''.

• Take the sodium fusion extract and acidify with CH3COOH and add lead acetate, black ppt. indicates the presence of Sulphur.

• When both Nitrogen and sulphur oresent, but not used excess of Na during fusion extract, then NaSCN does not convert to NaCN and Na2S. Hence the following test should be used.

       

• Oxidation test for sulphur detection: Fuse organic compound with Na2CO3 and KNO3, if sulphur is present in organic compound it changes to Na2SO4. Extract the fused mass with water and then filter and add BaCl2 solution, white precipitate ( BaSO4) which is insoluble in mineral acids-indicates the presence of sulphur

                          

  (c) Detection of halogens:

•  If organic compound contain N/S/ and halogens, then sodium fusion extract contain NaCN/Na2S/ and NaX. So, before testing for halogens first we have to treat fusion extract with Conc. HNO3 which removes NaCN/Na2S ( Otherwise these interfere with tests of NaX). Conc. HNO3 decomposes NaCn and Na2S to HCN(g) and H2S(g). 

Now cool the extract and then add few drops of AgNO3 solution, formation of white ppt soluble in dil.NH4OH indicates the presence of Cl, Pale yellow ppt soluble in conc.NH4OH indicates the presence of Br and if yellow ppt. insoluble in NH4OH indiactes the presence of Iodine.

(d) Detection of Phosphorous:

• If we strongly heat the mixture of organic compound with sodium peroxide  and Na2CO3 then all the phosphorous present in the organic compound oxidises to phosphate. Extract the fused mass with water and filter the solution. Boil the filtrate with conc. HNO3 and add ammonium molybdate- yellow ppt. indicates the presence of ''P''.

GILMAN'S REAGENT

GILMAN'S REAGENT

Dialkyl lithium cuprates( Gilman's reagent) are very important organo metallic reagents in organic synthesis. These can be prepared by reacting two equivalents of organo lithium reagents with  one equivalent of copper(I) halides (generally bromides and iodides) at low temperatures in the solvent ether or THF.

Applications:
1. Gilman's reagent used to form new C-C bond in coupling reaction with alkyl halides (Corey-House synthesis to make alkanes)

• Methyl and primary alkyl iodides are preferred
• This is suitable method than Wurtz reaction to make alkanes with odd number of carbon atoms

2. Gilman's reagens mainly adds to conjugated ketones and aldehydes through 1,4-conjugate addition. Reaction gives more yield in presence of Trimethyl silyl chloride (TMS Chloride) when can be deprotected at the end through aqueous work-up. 

Whereas the addition of Grignard's reagent to conjugated carbonyls proceeds through 1,2-conjugate addition.

INTRODUCTION

DEAR ALL MY FRIENDS,

I WANT TO SHARE ALL THE ARTICLES, CONTEMPORARY ISSUES IN CHEMISTRY, NOTES TO THE STUDENTS IN A SIMPLE  AND UNDERSTANDABLE WAY, ADVANCED JOURNAL ARTICLE BASED QUESTIONS(HELPFUL TO THE TEACHERS) AND SO ON.

I WILL DISCUSS QUESTIONS FROM VARIOUS INDIAN ENTRANCE EXAMINATIONS (IIT, NEET, GATE,CSIR, M.SC AND UPSE ...) AND TRY TO SHARE THE BOUNDLESS KNOWLEDGE AND WANT TO LEARN PARALLEL MYSELF.

I WILL DISCUSS SOME IMPORTANT CHAPTERS FROM ADVANCED BOOKS (CLAYDEN ORGANIC CHEMISTRY , CHEMISTRY OF ELEMENTS,  PHYSICAL CHEMISTRY P.W ATKINS, INORGANIC CHEMISTRY SHRIVER & ATKINS, HOUSECRAFT INORGANIC CHEMISTRY....)

THANKS AND REGARDS

(KISHORE.S)