3.7. Pyridinium Chloro Chromate (PCC):

Transcription

1 xidation 3.7. Pyridinium hloro hromate (P): 97 l l r r 3 r l P is a very important oxidising reagent which will give controlled oxidation in the case of primary alcohol. It does not give over oxidation during the oxidation of primary alcohol. It does not oxidised t-alcohol. But in the case of 3º allylic alcohol having atleast one -hydrogen through [3, 3] sigma tropic rearrangement. P will give oxidation with the migration of double bond. P 2 o over oxidation or P/ 2 l 2 P or P/ 2 l 2 P [xidation through 3, 3 ST] Acid catalysed oxidation of alcohol with double bond present in the compound, by P cyclization takes place. Bn Bn P/ 2 l 2 l If P reagent is used with buffer solution such as 4 l/ 2 (Buffer), a 2 P 4 /a 2 P 4, as 3 / 2, ( 3 a ) (Buffer) then no acid catalysed cyclization or no any acid catalysed reaction will occur. Bn Bn P/ 3 a In 1, 4 diols or 1.5 diols P reagent is used then it will give controlled oxidation and form cyclic ester or lactone ring. P

2 98 xidation Example: t-bu 2 Si 1.5 eq., Py r 3 l t-bu 2 Si t-bu t-bu Et 1.4 eq. (Py )r Et 3.8. Pyridinium Dichromate (PD): r r PD is soluble in 2, DMF and DMS but sparingly soluble in 2 l 2 or l 3. The reagent is less acidic than P. ence, oxidation in 2 l 2 can be carried out under nearly neutral conditions. This permits the conversion of primary alcohol containing acid sensitive group into the corresponding aldehyde or ketones. PD 2 l 2 In DMF solution however PD oxidizes non-conjugated primary alcohol to corresponding carboxylic acid and in 2 l 2 to give aldehyde. PD DMF PD 2 l 2 In carboxylic acid solvent, PD oxidizes primary alcohol to anhydrides and in the presence of liq. 3 convert into amide. PD/liq. 3 2 PD/Ac 2 3 PD any solvent 3.9. ollins-atclifte eagent: r 3 2 l 2

3 xidation ollins reagent is a mild reagaent for the oxidation of alcohols that contain acid sensitive groups. ollins reagent prepared by adding r 3 to a mixture of pyridine- 2 l 2. r 3 18º 2 l 2 [r 3.Py 2 ] ollins reagent primary alcohol oxidised to aldehye and secondary alcohol to ketone respectively. 2 collins reagent collins reagent Jones reagent: r3 2S4 2 acetone (a) r 3, pyridine, 2 l 2 (b) Add alcohols substrate (c) work up 90% r, a2r27 2S4 2 acetone xidation of primary alcohols with Jones eagent may result in the conversion of the aldehyde initially formed to the corresponding carboxylic acids. 2 r 3 / 2 S 4 acetone Jones reagent acetone a2 r 7, 2 S 4 2, Et 2, r.t. Jones reagent used for the oxidation of primary and secondary alcohols and does not effect any group present in the compound. Jones reagent

4 100 xidation Swern xidation: DMS l 2 2l2 Activation of dimethylsulfoxide (DMS) by oxalyl chloride produce intermediate (A) that decompose rapidly at 78º to furnish chlorodimethylsulfonium chloride (B) along with and 2. eaction of (B) with 2 (or 2 ) leads to intermediate (), which upon addition of Et 3 and warming afford the corresponding carbonyl compound 2 S, Et3 l 2 S (l) 2 2 l 2, 78º S l l 2 S l l 2 S Et 3.l 2 S (A) Add base Et 3 warm S (B) 2 78º DMS/(l) 2 / 60º 2 Et [1º-alcohol] 3 DMS/(l) 2 / 60º Et 3 (a) DMS (l) 2 2 l 2, 50º (b) Et 3, 50 to 0º (c) 2 workup Swern n [] n Ph 3 P = 2 M 78º to 20º n If base is not present then u substitution will occur at the end of reaction and swern substition will occur. 2 DMS/(l) 2 / 60º then 0 50º ucleophilic substitution DMS/(l) 2 / 60º then, 0 50º Swern substitute 2 l l

5 xidation 101 DMS, (l) 2 2 l 2, 78º then Et 3 Swern reagent can also be used for the oxidation of primary amide substrate into nitrile or cyanide. 2 1º amide DMS/(l) 2 / 60º Et 3 itrile 2 DMS/(l) 2 / 60º Et Moffatt oxidation: [D/DMS] D/DMS 2 D/DMS 2 DMP/ 2 l 2 chanism: DMP/ 2 l 2 Ac I Ac Ac 2 Ac I Ac Ac Ac IBX(2.5) eq. DMS IBX(2.2) eq. DMS

6 102 xidation DMP(1.3 eq) 2 l 2, 0º equivalent 2 l 2, room temperature 4 19 When dicyclohexyl carbodiamide reagent is mixed with DMS oxidizing reagent then it is specially used for the oxidation of steroidal alcohol. Bn Bn D/DMS D/DMS

7 xidation Dess-Martin Periodinane: DMP-xidation I xone 2, 70º I Ac 2 Ts(cat.), 80º I Ac Ac Ac DMP IBX It is a hypervalent iodine based oxidising reagent which is highly specific for the oxidation of primary and secondary alcohol and does not effect any sensitive functional group. 1 eq. IBX DMS, r.t Tetrapropylammonium Perruthenate (TPAP): Pr 4 u 4 TPAP is an air stable oxidant for primary and secondary alcohols. It is used in catalytic amount in the presence of a o-oxidant such as -methylmorpholine--oxide (M). 2 TPAP(cat.) M u(iv) u(iv) u(vii) M TPAP tolerates a wide variety of functional groups including double bonds, enolates, halides epoxides, esters, and lactones. Protecting groups such as MEM, trityl, silyl and benzyl ethers, TP and acetals are not effected. TBS TPAP (5 mol%) M (1.5 eqi.) molecular sieves (500 mg/ mmol) 2 l 2 (2mL/mmol) TBS

8 104 xidation chanism: 2 u u u u u u Examples: TPAP/M TPAP DM/ Lactone Bn Bn t-buph 2 Si cat. TPAP, M, 25º t-buph 2 Si Activated Manganese Dioxide(Mn 2 ): Mnl KMn Mn ppt Mn 2 is highly chemoselective oxidant-allylic, Benzylic, and propargylic alcohols are oxidised faster than saturated alcohols. The oxidation takes place under mild condition in 2, acetone and l 3. Mn 2 (i) acetone

9 xidation 105 (ii) Mn 2 acetone Ph Ph (iii) Mn 2 Bn Bn (iv) Boc 10 eq. Mn 2 Ph 3 P = 2 l 3, reflux Boc 2 KMn 4 (absored on a solid support) and useful alternative to Mn 2 in the oxidation of allylic or benzylic alcohol Silver carbonate on elite Fetizon s reagent : Ag elite 2 3 Fetizon s reagent will give chemoselective oxidation of secondary alcohols in the presence of primary alcohols. Ease of alcohol oxidation: Allylic Benzylic 2º 1º less hindered 1º Ag 2 3 /celite Benzene Ag 2 3 (5 eq) xidation of 1, 4 or 1, 5 alcohols to gives 5 or 6 membered lactones respectively. Ag 2 3 (10 eq) elite, benzene, reflux

10 106 xidation Ag 2 3 on celite Ph, reflux , 2, 6, 6 Tetramethyl 1-Piperidinyloxy (TEMP) TEMP is a commercially available nitroxyl radical-containing reagent that catalyses the oxidation of primary and secondary alcohol. TEMP primary alcohols are oxidised faster than secondary. 2 TEMP 2 l 2 TEMP 2 l 2 TEMP 2 l 2 2 _ X Ph bz al, abr, 2 l 2, 2 TEMP (at.) 0 5º Ph bz TEMP, 2 ul, DMF TBS TBS t-bu Ph 2 1 mol % TEMP 2 l 2, 5º al t-bu Ph 2

11 xidation eric Ammonium itrate (A): hemoselective oxidation of a secondary group in the presence of a primary group has been achieved with ( 4 ) 2 e( 3 ) 6, abr 3. A does not affect any double bond present in the group ( 4 ) 2 e( 3 ) 6 A A ( 4 ) 2 l ( 3 ) 6 abr 3 3, 80º A TF, Sodium ypochlorite (al): hemoselective oxidation of a secondary group in the presence of a primary group is possible with al in aqueous acetic acid aq. al 2 (1.05 eq) A 3 Aq. al (1.05 eq) A al 2 2 2, 2, a 2 P 4

12 108 xidation lenium Dioxide: 2, 2 / A, 2 / 2, 2 / A 2 2 is specially used for the oxidation of allylic carbon, having atleast one allylic hydrogen into allylic alcohol. chanism based on following pericyclic reaction. (i) Ene reaction (ii) [2, 3] Sigmatropic shift 3 2 chanism: 2 (i) 2 2 Ene reaction 2 (ii) [2, 3] Sigmatropic shift () 2 lenium dioxide exhibits a useful stereochemistry in reaction with trisubstituted gem-dimethyl alkenes. The products are always predominantly the E-allylic alcohols. In this reaction the methyl group trans to main chain will react rather than the cis, thus only one (E) isomer is formed. 3 Et excess 3 2 Tri-substituted alkenes are oxidised selectively at the more substituted end of double bond including that the ene reaction is electrophilic in character. Tri-substituted alkenes are preferentially oxidised at one of the allylic group at the di-substituted carbon When double bond is in the ring, oxidation whenever possible occurs with in the ring and again to more substituted end of the double bond. (Indicate that ene reaction electrophilic in nature) t-bu

13 xidation 109 In the case of terminal alkenes, allylic rearrangement takes place (ormal product) 3 2 (earrangement product) xidation of alkynes: 2 with small amount of conc. 2 S 4 2, 2, 3 2, 3 Ph Ph 2, Ph Ph chanism: xidation of arbonyl ompound: 2 oxidises -carbon of carbonyl group. This oxidation can only be possible if carbon has at least two hydrogen. 2 chanism: If water present 2, 89º 2 /A 2, 89º Dioxane 2 2 2

14 110 xidation In absence of water: (i) Ph 2 Ph 2 Ph Ph (ii) ote: eactivity order [ 2 > 3 > ] eactivity of 2 group is more than 3 group. Because enolization of methylene group occurs more readily than methyl group Picoline 2

15 xidation Et 2 2 Et 2 Et 2 Et /a 3 3 / 2 /30º Dehydrogenation: 2 used to dehydrogenate 1, 4-dicarbonyl compound and 1, 2 diarylethane Ar Ar Ar Ar chanism: 2 2 () 2

16 112 xidation (i) Ph 2 2 Ph 2 Ph Ph (ii) 2 2 Et 2 Et Et Et Acetic acid undergoes dehydration to give succinic acid succinic acid ydrated form of 2 : _ 2 [2, 3] ST * E-lectivity: 0.5 Mol 2 95% 2 5 eflux 2 2 must be equatorial in the above transition state. When there is no allylic hydrogen in the substrate then oxidation of only = occurs as shown below

17 xidation 113 2, -dicarbonyl compound * The alcohols that are initial product can be further oxidized to carbonyl group by 2, and the conjugated carbonyl compound is usually isolated. If the alcohol is the desired product, the oxidation can be run in acetic acid solvent in which acetic ester are formed A 2 omplex , Dicyclohexylcarbodiimide (D): 35% 18% 8% Introduction: D is a powerful dehydrating agent are stored under anhydrous conditions. It is commercially available as a waxy low melting solid, which melt at 34 35º. Preparation: (i) By oxidation of DU with p-toluenesolfonyl chloride in hot pyridine p S 2 l hot Py (ii) By heating DU with mercuric oxide (g 2 ) DU g 2 D 2 Applications: (A) Synthesis of esters and amides: ' D ' DU chanism:

18 114 xidation ' ' ' Ester ' 2 ' Amide * 2 2 D 2 (B) Miscellaneous Functions : -hydroxyester/ -hydroxy ketons on reaction with D undergoes dehydration as shown in the follwoing examples. - t But - t But D D D D D 2 S 2 S 2 1 D 2 1

19 xidation 115 _ 2 DU () Synthesis of organic diacyl peroxide 2 Ph Ph D Ph Ph 2DU 2 2 (D) Ether Formation Ph Et or or Ar S D Ph Et or Ar S Et 2 DU (E) Formation of Anhydrides ' D ' DU 2 (F) Dehydroxylation of alcohols: D Pd 2 DU (G) Formation of Lactone and Lactams: D -Lactone 3 3