Organisk Kemi for Biologer

Transkript

1 rganisk Kemi for Biologer Supplerende noter Kemisk Institut Aarhus Universitet Forår 2010 Steen Uttrup Pedersen

2 Indholdsfortegnelse Bindingsforhold.3 eduktion med NaB 4 og LiAl 4.3 versigt over Grignard reaktioner...4 Wolff-Kishner reduktion...5 Wittig reaktion...6 Diazonium salte (Sandmeyer reaktionen)...8 Diazonium koblingsreaktioner...10 yanohydriner

3 Bindingsforhold eduktion med NaB 4 og LiAl 4 (addition af - ) eaktions Produkter eagens LiAl 4 i NaB 4 i methanol - støkiometri ether Aldehyd 1 Alkohol 1 Alkohol 1 Keton 2 Alkohol 2 Alkohol 1 Syre 1 Alkohol eagerer med 2(LiAl 4 ) hlorid methanol til ester Ester 1 Alkohol Langsom red. 2(LiAl 4 ) arboxyl 1 Alkohol - reagerer med + 3(LiAl 4 ) syre og giver 2 arboxylat 1 Alkohol ingen reaktion 2(LiAl 4 ) Amid Amin ingen reaktion 2(LiAl 4 ) Nitril 1 Amin ingen reaktion 2(LiAl 4 ) Alken, aromat ingen reaktion ingen reaktion 0 3

4 versigt over Grignard reaktioner (supplement til McMurry) eaktanter MgX + MgX + MgX + MgX + MgX + ' ' ' ' Formaldehyd Aldehyd Keton Ester '' '' arboxyl syre syre/base ' '' ' ' Produkter Alkan + Primær alkohol Sekundær alkohol Tertiær alkohol Tertiær alkohol ' - MgX + 2 arboxyl syre Kuldioxid - MgX Vand alkan MgX + Epoxid MgX + ' N ' 4

5 Wolff-Kishner reduktion: Process for reducing a ketone or aldehyde to an alkane by reaction with K and hydrazine 2 N-N 2, Na ' o Δ, ' An important variant of imine formation involves the treatment of a ketone or aldehyde with hydrazine, 2 N-N 2, in the presence of strong base. alled the Wolff- Kishner reaction after its discoverers, the process is a useful method for converting ketones or aldehydes into alkanes, 2 = 2 2. The reaction involves initial formation of an imine intermediate called a hydrazone, followed by loss of nitrogen and formation of the alkane product. Mekanisme: ' ' ' ' : N 2 + N N 2 : + N N 2 N 2 N N 2 N 2 N 2 ydrazon ' ' ' ' N 2 + ' N N - - N N 2 N N - N N ydrazon Eksempel: ' ' N N N 2 2 NN 2 Propiophenone K A hydrazone Propylbenzene (82%) 5

6 Wittig reaktion (alken-dannelse) Nucleophilic Addition of Phosphorus Ylides: The Wittig eaction Ph X ' Alkylhalogenid med α- 1) Ph 3 P 2) Butyllithium ' ' - P Ph Ph Ph + P Ph Ph '' ''' keton el. aldehyd '' ' Alken ''' Ketones and aldehydes can be converted into alkenes by means of the Wittig reaction. In this process, a phosphorus ylide, 2 P( 6 5 ) 3 adds to the ketone or aldehyde to yield an intermediate that reacts further to yield an alkene. The overall result is replacement of the carbonyl oxygen atom by the organic fragment originally bonded to phosphorus. A ketone or aldehyde 2 P( 6 5 ) 3 (an ylide) 2 P( 6 5 ) 3 Intermediate + ( 6 5 ) 3 P An alkene The phosphorus ylides necessary for Wittig reaction are easily prepared by S N 2 reaction of primary (but not secondary or tertiary) alkyl halides with triphenyl- 6

7 phosphine, ( 6 5 ) 3 P:, followed by treatment with base. Since triorganophosphines are generally excellent nucleophiles in S N 2 reactions, high yields of stable, crystalline tetraorganophosphonium salts are usually obtained. The proton on the carbon atom next to the positively charged phosphorus is acidic and can be removed by a strong base such as sodium hydride or butyllithium (BuLi) to generate the ylide. For example: Br - S ( 6 5 ) 3 P 3 Br N 2 reaction + ( 6 5 ) 3 P 3 BuLi TF ( 6 5 ) 3 P 2 + Butane + LiBr A great many mono-, di-, and trisubstituted alkenes can be prepared from the appropriate combination of phosphorane and ketone or aldehyde. Tetrasubstituted alkenes cannot be prepared, however. The great value of the Wittig reaction is that pure alkenes of known structure are prepared. The alkene double bond is always exactly where the carbonyl group was in the precursor, and no product mixtures (other than E,Z isomers) are formed. For example, reaction of cyclohexanone with methylenetriphenylphosphorane yields the single pure alkene product, methylenecyclohexane, whereas the alternative synthesis by addition of methylmagnesium bromide to cyclohexanone followed by acidcatalyzed dehydration leads to a mixture of two alkenes MgBr 2. 2 S Methylcyclohexene Methylenecyclohexane 2 yclohexanone ( 6 5 ) 3 P 2 TF solvent + ( 6 5 ) 3 P Methylenecyclohexane (84%) 7

8 Diazonium salte (Sandmeyer eaktionen) 8

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11 Aryldiazonium salte kan også substitueres med fluor (F) ved behandling med tetrafluorborsyre + varme: 1) BF 4 2) varme Ar-N + 2 Ar-F yanohydriner. Aldehyder og uhindrede ketoner reagerer med N og giver cyanohydriner. eaktionen er en ligevægt men i modsætning til additionen af vand eller andre syrer (X) er ligevægten forskudt mod additionsproduktet (cyanohydrinen). eaktionen foregår via en nukleofil additionsmekanisme: - - :N N N N N - Dannelsen af cyanohydriner er ofte fordelagtig fordi cyanogruppen enten kan reduceres med LiAl 4 eller hydrolyseres med varm vandig syre f.eks. l(aq). erved forlænges kulstofskelettet med et samtidig med at, der introduceres nye funktionellegrupper, som kan tjene til yderligere modifikationer. Nedenfor er ovennævnte reaktion eksemplificeret med benzaldehyd, som danner mandelonitrile, der enten kan reduceres eller hydrolyseres til henholdsvis 2-amino-1-phenylethanol eller mandelic acid: 2 N 2 N 1) LiAl 4, TF 2) 2 N 3 + Δ 11

12 eaktionen med cyanohydriner finder bl.a. anvendelse indenfor kulhydrater, hvor metoden kan anvendes til at forlænge naturlige aldoser. D-kobling af carboxyl syre og aminer (peptid-syntese) 12