peter pazmany catholic university · raspberry ketone. lily-of-the-valley aldehyde. organic and...

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Development of Complex Curricula for Molecular Bionics and Infobionics Programs within a consortial* framework**

Consortium leader

PETER PAZMANY CATHOLIC UNIVERSITYConsortium members

SEMMELWEIS UNIVERSITY, DIALOG CAMPUS PUBLISHER

The Project has been realised with the support of the European Union and has been co-financed by the European Social Fund ***

**Molekuláris bionika és Infobionika Szakok tananyagának komplex fejlesztése konzorciumi keretben

***A projekt az Európai Unió támogatásával, az Európai Szociális Alap társfinanszírozásával valósul meg.

PETER PAZMANY

CATHOLIC UNIVERSITYSEMMELWEIS

UNIVERSITY

2011.09.14.. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 2

Carbonyl compounds(Karbonilcsoportot tartalmazó vegyületek)

Organic and Biochemistry(Szerves és Biokémia )

semmelweis-egyetem.hu

Compiled by dr. Péter Mátyuswith contribution by dr. Gábor Krajsovszky

Formatted by dr. Balázs Balogh

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Organic and Biochemistry: Carbonyl compounds

Table of Contents

1. Aldehydes 6 – 92. Ketones 10 – 143. Reactions of aldehydes and ketones 15 – 174. Addition and condensation reactions 18 – 285. Reactions through enolate anion 29 – 36

6. Carboxylic acids and carboxylic acid derivatives 37 – 52

7. Acid halides 53 – 56

8. Esters 57 – 59

9. Acid amides 60 – 63

10. Acid nitriles 64 – 65

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Table of Contents

11. Physical properties 66 – 6612. Chemical properties 67 – 7613. Substituted acids 77 – 8014. Lactones (cyclic esters) and lactams (cyclic amides) 81 – 8115. Hydroxy carboxylic acids 82 – 83

16. Amino acids 84 – 90

17. Amino acids: synthesis 91 – 93

18. Oxocarboxylic acids 94 – 94

19. Reactions of CH acids 95 – 96

20. Carbonic acid derivatives 97 – 99

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Carbonyl compoundsC O containing carbonyl group (carbon-oxygen double bond)

I. Aldehydes a -CHO group is connected to a C-atoma) substitutive name (IUPAC name)

as a prefix: formylas a suffix: -al, carbaldehyde

CH3 CH2 CH2 CHO OCH CH2 CH CH CHO12345

butanal pent-2-enedial

OCH CH2 CH CH2 CH2 CHO

CH2 CHO

1 2 3 4 5 6 CHO

3-formylmethylhexanedial cyclohexanecarbaldehyde

b) common namesstem of common name of the corresponding carboxylic acid + aldehyde

5


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Aldehyde Carboxylic acid

H CO

HH C

O

OH

CO

HCH3 CH3 C

O

OH

C2H5 CO

HC

OH

OC2H5

C3H7 CO

HC

O

OHC3H7

formaldehyde

acetaldehyde

propionaldehyde

butyraldehyde

a. formicumformic acid

a. aceticumacetic acid

a. propionicumpropionic acid

a. butyricumbutyric acid


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Aldehyde Common names Carboxylic acid

i-C3H7 CO

Hisobutyraldehyde C

O

OHC3H7i- a. isobutyricum

isobutyric acid

C4H9 CO

Hvaleraldehyde CC4H9

O

OH

a. valerianicumvaleric acid

HO CH2 CO

Hglycolaldehyde CH2HO C

O

OH

a. glycolicumglycolic acid

CH

CH2 CH2 CO O

Hsuccinaldehyde C

O

HOCH2 CH2 C

O

OH

a. succinicumsuccinic acid

C

O

H benzaldehydeC

OH

Oa. benzoicumbenzoic acid


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CHO

OCH3

HO

COOH

OCH3

HO

vanillin

vanillic acid

CHO

OO

COOH

OO

piperonal

piperonylic acid

HOOH

CHO

protocatechualdehyde

COOH

HOOH

protocatechuic acid


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Aldehyde Carboxylic acid

CHO

OH

COOH

OH

H3CO

CHO COOH

H3CO

CHO

OCH3

H3CO

COOH

OCH3

H3CO

salicylaldehyde salicylic acid

p-anisaldehyde

veratraldehyde

p-anisic acid

veratric acid


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II. Ketones containing a carbonyl group with two R groups.C Owithin a chain

a) substitutive name (IUPAC name)as a prefix: oxo-as a suffix: -one [ ketone]

Cl CH2 CH C CH2 CH3

CH3 O

1 2 3 4 5CH3 C CH2 COOH

O

4 3 2 1

H2C CH CH2 C CH3

O

12345 O

1-chloro-2-methylpentan-3-one 3-oxobutyric acid

4-penten-2-one cyclohexanone


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b) radicofunctional

H3C C CH2CH3

O

ketoneethyl methyl ketone

c) aromatic ketones

C

O

CH3acetyl → acetophenone

C

O

benzoyl → benzophenone


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Synthesis1. Methods for preparation of both aldehydes and ketones

- Oxidation

Jones reagent: H2CrO4 • H2SO4 (water-acetone)Collins reagent: CrO3 • pyridineMnO2 active (← KMnO4 + MnSO4)

Dehydrogenation catalyst: Cu-Cr oxide


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- By hydration of acetylenes

2. Syntheses of aldehydes

a) By reduction of carboxylic acid derivatives

- From acid chlorides: Rosenmund reaction

R C CHH2SO4 R C CH2

OHR C

OCH3Hg2+- salt

enol


H2

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Some important carbonyl compounds

- butyrophenones (antipsychotic agents)

O

F C (CH2)3 R

e.g., haloperidol

- Steroid hormones

- Fragrances and flavours

HO

(CH2)2C CH3

O

HCHO

CCH3

CH3

HO

H

raspberry ketone lily-of-the-valley aldehyde


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I. Addition reactions

II. Enolate chemistry

III. Oxidation-Reduction

Reactions of aldehydes and ketones


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Reactions of carbonyl compounds

1. Nucleophilic addition to the carbonyl groupunder basic conditions:

Nu C O Nu CO

Nu C

OHδ+ δ− H+

tetrahedral intermediate

under acidic conditions:

COH

NuH+

Nu

C OHH

C OC O


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2. Reaction of the α carbon atomenolate / enol formation → electrophilic substitutionon the α carbon

by base catalysis: → enolate anion

BO O

E+

EOO

H

by acid catalysis: → enol

EO

E+

OH

B

HOH

H+O


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I. Addition and condensation reactions

- Addition → tetrahedral intermediate or product- Condensation = addition + elimination

tetrahedral intermediate product- H2O

a) Addition of water

b) Addition of alcoholStep 1.

‘hemiacetal’

CH3 CH2 C OH

+ H2O CH3 CH2 COH

HOH

CH3 C OH

HCH3 C

OHH

CH3OHCH3 C

OH

HOCH3 H+

aldehyde hydrate


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Step 2.

‘acetal’

CH3OHH3C C

OCH3

HOCH3

H

-H H3C COCH3OCH3

H

CH3 COH

HOCH3

HCH3 C

OH2

HOCH3

-H2OCH3 C

OCH3

H

Step 1. (with base catalysis)

hemiacetal

CH3 COH

HOCH3

-H

HCH3 C

O

HOCH3O CH3CH3 C

OH


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c) Addition of sodium hydrogen sulfite

R CO

R'R C

OHSO3

R'Na H

R CO

R'

R’ = H, alkyl

aromatic aldehydes ±aromatic ketones –

adduct

d) Addition of HCN

CR

R'O C

R

R'

CN

OH

HCN

( B)

CN(if R=Ar, R’=H)

ArCOAr : does not react!ArCOR : poor reactivityArCHO : affords benzoin condensation

cyanohydrine


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acyloin

Ar = Ph → benzoin

benzoin condensation


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e) Wittig reaction → see preparation of olefinesf) Addition of acetylenes → see acetylenesg) Addition of Grignard compound → see preparation of alcohols

Note: side reactions are possible in the following cases

a) with a sterically hindered ketone → enolisation

CH

CO

R R'MgXR'H + C C R

OH+

b) with a sterically hindered Grignard compound → reduction

COH

H

COMgX

+CO

HC C MgX C C

H


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h) Reduction by metal hydrides → see alcohols


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i) Reaction of amines- NH3

O

NH2

OH NH

hemiaminal imine

- RNH2

O N-RSchiff's base

- R2NH CH

O

CH C

NR2

OH

CNR2

C

enamine

- R3N

OCNR3X

OH


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A = HO - hydroxilamine OXIMEA = NH2 - hydrazine HYDRAZONEA = semicarbazide SEMICARBAZONE

j) Aldol reaction

A - NH2O N-A

+

C CR1

R2C

O

R

OH

HC C

O

R

C R2R1

OR1 C

O

R2

C C

O

R


H2N C NH

O

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H2C C

O

HH

H2C C

O

CH3H

H2C C

O

OC2H5H

pKa 17 19 24


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Reactions of α,β-unsaturated carbonyl compounds

O

Nu

HNu

O

HNu

Nu

OH

'1,4 - Addition'

and / or

'1,2 - Addition'

1 2 3

4


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Aspects of regio- and stereoselectivity

1. Regiochemistry of the nucleophilic addition to α,β-unsaturatedcompounds:

strongly basic nucleophiles → 1,2

weakly basic nucleophiles → 1,4


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II. Reactions through enolate anion

Oxo-enol tautomerisation

CH3 C CH3O

CH3 COH

CH2

oxo enol

CH3 CO

CH2CO

CH3

OCH3 C

OH

CH C CH3

84 %16 %

10-4 %


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H CCH2

CH2

allyl anion enolate anion

H CO

CH2

H CO

CH2

H CCH2

CH2

H CCH2

CH2

H CO

CH2


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Electrophilic substitution

O1. LiNPr2

2. CH3I

OCH3

pKa = 17

-70°C

OLi

i

CH3I-70°C

pKa = 40

LiNPr2i

H3CH3C

NH

2

CH


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RC

O

CH3

X2acid

RC

O

CH2X

Halogenation at the α-position

RC

O

CH3 RC

O

CH2

B- I I

RC

O

CH2I

δ+

δ−

δ−

δ+R

C

O

CH2I B-

RC

O

CH

I

I2

RC

O

CHI2

RC

O

CHI2 RC

O

CI3 RC

O

O+ HCI3


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Disproportionation

Cannizzaro reaction

Aldehydes without α-H carboxylic acid + alcoholHO

R CH

O OHR C H

OH

OCH RO

R CO

OHR C

O

HH R C

O

ORCH2OH


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Oxidation-reduction

Reduction

- Kizsnyer-Wolff

see paraffins

- Clemmensen

see paraffins

- metal hydrides (Meerwein-Ponndorf-Verley)

see nuclephilic addition (hydride)

see alcohols


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Oxidation

R-CHO R-COOH O2/peracidsH2O2KMnO4O

HNO3HOOC (CH2)4 COOH

Ph CO

CH3SeO2 Ph C

OCHO

O

RCO3H O

O

(Baeyer-Williger)


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Some important aldehydes:

Formaldehyde: Its 40% aqueous solution is formalin

Acetaldehyde

O

O O

O

H

H3C

H

CH3

H CH3

H CH3

H2SO4H2SO4

HClH2SO4,

H3C

O O

OH H

HH3C

CH3

H3C CO

H

ParaldehydeMetaldehyde


n = 10 - 100

paraformaldehyde

n HOCH2OH HO(CH2 O)n-1CH2OH

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Carboxylic acids and carboxylic acid derivatives

H C

O

O H

1.2

125°

0.97

1.34111°

124°

Carboxylic acids: compounds containing

CO

OHgroup

R CO

acyl group


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Carboxylic acid derivatives:

Z: heteroatom, or groupZ: halogen → acid halide

acyloxy → acid anhydridealkyl/aryloxy → esterNR1R2 → carboxamide

→ nitrile

→ imidate→ imidic acid, R=H

meaning of


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CO

OH

Carboxylic acid

CO

O OH

Peroxy acid


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C

Cl

O O OH O

OOH

O

O

2

Mg

m-chloroperoxybenzoic acid magnesium monoperoxyphthalate


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CO

OHC

OH

OHOH

carboxylic acid orthocarboxylic acid

CO

ORC

OR

OROR

ester orthoester


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Imid-, hydrazon-, hydroxime- and hydroxamic acid

Tiocarboxylic acid


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1. Classification of carboxylic acids

monocarboxylic aciddicarboxylic acid

- according to the hydrocarbon skeleton attached to the carboxylic group:

saturated unsaturated aromatic


- according to the number and position of the carboxylic group:

COOH

CH3 COOH HOOC COOH CH2 COOHHOOC1,2 1,3

CH2 COOHCH3 CH COOHCH2

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2. Nomenclature


-substitutive: as a prefix: carboxy-as a suffix: -oic acid

e.g.,

butanoic acid

3-hydroxy-2-methyl-4-oxo-pentanedioic acid

COOH

(CH2)2 COOHCH3

HOOC CH

CH3

CH C

OH O

COOH

cyclohexanecarboxylic acid

COOH

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Trivial names: see aldehydes/ketones, moreover:

a) saturated monocarboxylic acids/and appropriate acyl groups

CH3(CH2)4COOH caproic acid caproyl

CH3(CH2)10COOH lauric acid lauroyl

CH3(CH2)12COOH myristic acid myristoyl

CH3(CH2)14COOH palmitic acid palmitoyl

CH3(CH2)16COOH stearic acid stearoyl


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b) Saturated dicarboxylic acids

HOOC-COOH oxalic acid oxalyl

HOOC-CH2-COOH malonic acid malonyl

HOOC-(CH2)2-COOH succinic acid succinyl

HOOC-(CH2)3-COOH glutaric acid glutaryl

HOOC-(CH2)4-COOH adipinic acid adipoyl

HOOC-(CH2)4-COOH pimelinic acid pimeloyl


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c) Unsaturated carboxylic acids:

acrylic acid acryloyl

propiolic acid propioloyl

crotonic acid crotonyl

isocrotonic acid isocrotonyl


CH2 CH COOH

CH C COOH

C C

CH3

COOH

H

H

C C

H

COOH

H

CH3

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(cis 9-octadecenoic acid)

9,12-octadecadienic acid linolic acid linoyl

9,12,15-octadecatrienic acid linolenic acid linolenoyl

cis butenedioic acid maleinic acid malenoyl

trans butenedioic acid fumaric acid fumaroyl

oleic acid oleoyl


CH3

O

OH

C C (CH2)7(CH2)7

H H

CH3 COOH

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d) Aromatic carboxylic acids

benzoic acid benzoyl

naphthoic acidnaphthoyl

phthalic acidphthaloyl

isophthalic acidisophthaloyl

terephthalic acidterephthaloyl


COOH COOH

COOH

COOH

COOH

COOH

COOH

COOH

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Acidic residue:

carboxylic acid → carboxylate

3. Preparation of carboxylic acids

a) Preparative methods

- Oxidation

or Na2Cr2O7 / H2SO4

from alcoholsfrom aldehydesfrom ketones


R C

O-

O

NO2

CH3

NO2

COOH

KMnO4

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- From organometallic compounds

- From nitriles


CH3 CH2 CH CH3

MgBr

CO2CH3 CH2 CH CH3

CO2MgBr

CH3 CH2 CH CH3

COOH

H+

Li COOHCO2

H+

R XKCN

R CNH3O

+

R COOH

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Conditions of hydrolysis: - by acids- by bases - by enzymes


R C

OR'

O

R C

OH

O

b) From naturally occurring esters

- Fats: esters of longer carboxylic acids with glycerol- Waxes: esters of longer carboxylic acids with longer

monoalcohols

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Acid halides

Nomenclature: acyl group + halide

CH3 CO

ClC

O

BrCH2 C

O

Bracetyl chloride malonyl dibromide benzoyl chloride


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COOH

CO

Cl

3-(chloroformyl)cyclohexanecarboxylic acid

• Preparation: acid + phosphorus halide (PCl3, PCl5), or thionyl chloride (SOCl2)

Cl S

O

Cl SO2R CO

ClO SOCl+R C O

-HCl+R C

O

OH+

COOH PBr33 3 CO

Br+ H3PO3

CH2 C OHX

H3C CO

X


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Preparation of acid fluorides:

Preparation of acid anhydrides:

R CO

OH

R CO

OC

OR

,

Nomenclature:

acid acid anhydride

CO

OCH3C

O

H3Cacetic anhydride

CO

OCCH2

O

H3C

CH3

acetic propionicanhydride


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Preparation:

,

R CO

OC

OR

R COO +,

R COCl

Mixed anhydrides:


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Esters:

Nomenclature

methyl acetate

methyl hydrogen malonatesodium methyl malonate


H3C CO

O CH3

CH2 CO

OCH3

CO

ONa

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ethyl (2-methoxycarbonyl-phenyl)acetate

By traditional nomenclature:

benzoic acid ethyl ester

Orthoesters: esters of the (hypothetic) ortho acids

triethyl orthoacetate


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Preparation

CH3CO

OH

CH3OH/HCH3 C

O

OCH3

CH3CO

Z

HORCH3 C

O

ORacid anhydrideacid halogenide

CH3 CO

OCH3

ROH/RO v. HCH3 C

O

OR

CH3 CO

O Na

R X,

CH3 CO

OR,


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Acid amides

1o order

2o order 3o order


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NomenclaturePrimary amides: ‘ acid + amide’ → acid amide

‘carboxylic acid + amide’ → carboxamide

cyclohexanecarboxamide

Analogous name:

benzenesulfonamide

But: acetamide H3CCONH2

benzamide C6H5CONH2

succinamidic acidH2NOC(CH2)2COOH


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as acyl-amino group

4-(acetylamino)benzoic acid

4-(N-methylcyclohexyl-carbonylamino)benzoic acid

But:

N-methylbenzamide acetanilide N-methylbenzanilide


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Preparation:

By acylation of amines:

By heating of ammonium carboxylates:

By hydrolysis of nitriles:


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Acid nitriles:R C

O

OHR C N

Nomenclature• hydrocarbon + nitrile

CH3 (CH2)4 C Nhexanenitrile

N C (CH2)4 C Nhexanedinitrile

• carboxylic acid → carbonitrileCN

cyclohexanecarbonitrile

• trivial: acid → onitrilebut: acetonitrile!

• as a prefix: cyano-


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Preparation:

Imide esters:

R CO

NH2

- H2O

e.g., P2O5SOCl2/DMF

R C N

R CH N OH- H2OAc2O

R C N

R X + NaCN R C N

R C N:C N R isonitrile

nitrile

nitrile

PTCconditions

DMFor DMSO

R C N R OH,

HCl gasR C

NH

OR, HCl


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Physical properties

Monocarboxylic acids: are liquids up to C8their b.p.s are high due to dimeric associates (H bonding)the m.p. of the even-numbered carboxylic acids is higher, than that of the odd-numbered acids.

Dicarboxylic acids: m.p. of even-numbered > odd-numbered

Acid halides: of carboxylic acid derivatives, the lowest b.p.s

Esters have lower b.p.s than their carboxylic acid counterparts (no H bonding)

Acid anhydrides lower b.p.s than their acid halide counterparts

Acid amides high b.p., higher homologs are crystalline substances (dimeric associates)

Acid nitriles high dipole moment, → high b.p.


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Chemical properties of acid derivatives

1. Acidity:

carboxylic acids >> alcohols, but <<mineral acids

pKa

HCl

CH3COOH

CH3CH2OH

pKa

-7

4.76

16

1.27 /4.27

2.85 / 5.70

HOOC COOH

HOOC CH2 COOH

carboxylic acid amides

pKa ∼ 15CH3 CO

NH2

pKa ∼ 0

NH4+ pKa ∼ 9

CH3 COH

NH2


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2. Reactivity against nucleophiles

R’ = H / alkyl / aryl, thus it is a poor leaving groupC OR

R

,

+ XNu

RC O

elimination

X

RO

CNuaddition

X

RNu: C O


c.p. with aldehydes / ketones

2011.09.14.. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 69

The reactivity mainly depends on two opposite effects:

1. The greater is the -I effect of X, the higher the electrophilicityof carbonyl carbon atom is (accordingly it is more reactive)

2. Delocalization between one of the lone pairs of X (+M effect)and the C=O π-bond

Reactivity is decreased, since the ground state is more stabilized, than the transition state.

>X

C Oδ-

δ-2δ+

CO

X


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a) Acid halides-I effect of the halogen atom is dominating

b) Esters and amidesTheir reactivity is decreased by delocalization

Acylation reactionsH atom is replaced by an acyl group

O, S, N, C acylation

Reactivity order of acylating agents:ketene>acid halide>acid anhydride>ester>nitrile>amide, acid

H-Z

acylatingagent

R CO

Z


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Some important reactions of carboxylic acids and its derivatives

a) Carboxylic acidsDecarboxylation:

R CO

O Na

NaOH R H Na2CO3Δ

CO

O

-CO2

CO

HO CH2CO

H

O -CO2

CH3COOHC CH2HO

HOΔ


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b) Acid halides:

Preparation of acid azide

Schotten - Baumann acylation

NaN3R CO

XR C

O

N3

NaOHwater

Ar CO

Cl R2

R1

NH Ar CO

NR1

R2


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c) Esters:

Preparation of hydroxamic acid

Preparation of acid hydrazide

H2NOH RNH OH

CO

R CO

OR'R'OH

NH2NH2R CO

OR'R C

O

NHNH2R'OH


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R CO

Y

R`MgXR

CR`

OMgX

Y

RC

R`O

R`MgX

C OMgXR

R`R`

Y = OR``, Cl, Br

Preparation of tert-alcohol


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d) Acid amides:

Reaction with nitrous acid

HNO2-H2O N2R C

O

NH2

R CO

OH

-H2OHNO2 R C

O

N

R,

NOR CO

NHR,


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R CNHCl

C2H5OHR C

NH.HCl

OC2H5

2 C2H5OHR C

OC2H5OC2H5

OC2H5

Imidic acid esterhydrochloride

Preparation of orthoesters


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Substituted acids

Halo acidsHydroxy acidsAmino acidsOxo acidsHalo acids

R contains halogen

Nomenclature: halogen as prefix

3-bromopropionic acid 2-chlorocyclohexanecarboxylic acid

R COOH

BrCH2CH2COOH123

COOH

Cl


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Preparation:α-halogenated carboxylic acids

1. Hell-Vollhardt-Zelinsky

R-CH2-COOH + PX3 R-CH2COXenoloxo

CHR COH

Cl

CHR

ClC

OH

Cl

Cl Cl ClCH

R

ClC

O

Cl+ HCl

2 P + 3 X2 2 PX3


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2. From hydroxy acids:

R CH COOHOHHBr

R CHCl

CO

Cl

H2O

R CH COOHBr

R CH COOHCl

SOCl2


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Chemical propertiesReaction with base (NaOH)

R-CH2-CH2-CH-COOHCl

γ β αRCH2CH2CH-COOH

OHα-hydroxy acid

αβγRCH2-CH= CH-COOH

α,β - unsaturated acidR CH2CH CH COOH

Cl H

R-CH-CH2-CH2-COOHCl

γ

O ORγ - lactone

4-butanolideCH2-CH2CH2-CH2-COOHCl

δ

O Oδ - lactone

5-pentanolide


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O

O

O

O

O O O O

αβ

γ

δ

α-lactone β-lactone γ-lactone δ-lactone

N

O

HN

O

HN O

H

βγ α

N O

H

δ

α-lactam β-lactam γ-lactam δ-lactam

Lactones (cyclic esters) and lactams (cyclic amides)


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Hydroxy carboxylic acids

- Nomenclature* hydroxy as prefix* trivial names

Ph-CH-COOH

OHHOOC-CH2-C-CH2COOH

COOH

OHHO-CH2-COOH

mandelic acid citric acid glycolic acid

H3C-CH-COOHOH

HOOC-CH-CH2-COOH

OH OH

HOOC-CH-CH-COOH

OHlactic acid malic acid tartaric acid


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Preparation

1. From α-halo carboxylic acids

2. By hydrolysis of cyanohydrines (Strecker’s synthesis)

3. β-Hydroxy carboxylic acids: Reformatsky’s synthesis

R-CH-COOH R-CH-COOHCl OH

H3C COH

HCOOH

H2OHH3C C

OH

HCN

HCNH3C C

OH

Br CH2COOC2H5Zn

CH3CH3C

O

CH3C

H3CCH2 COOH

HO

β α


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Amino acids


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Amino acids

Amino and carboxyl groups are in the same molecule.

Classification- according to the order of the amine

(primary, secondary, tertiary, quaternary)- according to the number of amino and carboxyl groups

monoamino monocarboxylic aciddiamino monocarboxylic acidmonoamino dicarboxylic acid, etc.

- according to the structure of the carbon chainopen-chained, cyclic, aliphatic, aromatic

NH2 NH N N, , ,C

O

OH


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Open-chained, aliphatic, monoamino monocarboxylic acids

Aminoacetic acidAminoethanoic acidGlycine

α-aminopropionic acid 2-aminopropanoic acidAlanine

β-aminopropionic acid3-aminopropanoic acidβ-alanine

ε-aminocaproic acid6-aminohexanoic acidω-amino acids

H2N CH2 COOH H3C CH COOH

NH2

H2N CH2 CH2 COOH H2N (CH2)5 COOH


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Amino acids in proteins

Glycine (Gly) G Proline (Pro) P

R = CH3

Alanine (Ala) A Valine

(Val) VLeucine(Leu) L

Isoleucine(Ile) I

Methionine(Met) M

Phenylalanine(Phe) F

Serine(Ser) S

Cysteine(Cys) C

Threonine(Thr) T

H2N-CH2-COOH NH

COOHHR

H2N COOHamino acids

substituted on the α-C

CH3CH3

CH3

CH3

CH3CH3

S CH3OH SH

CH3

OH


2011.09.14.. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 88

R =

Tyrosine(Tyr) Y

Tryptophane(Trp) W

Histidine(His) H Asparagine

(Asn) N

Glutamine(Gln) Q

Aspartic acid (Asp)

Glutaminic acid(Glu) E

Lysine(Lys) K Arginine

(Arg) R

Amino acids forming proteins: glycine, alanine + 18 derivati-ves of alanine

these are chiral, with Lconfiguration, S (Cys R)

OHNH

NH

NNH2

O

NH2

O OHO OH

O

NH3 NH

NH2

NH2


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Chemical properties

1. Acid-base character

„aminoacetic acid”practically does not exist

glycine„zwitterionic system”

weak acid

weak base

Buffer effect of glycine

NH

CH2 COOHH

NH

CH2

HH C

O

O


H2O

H3O

H3N CH2 COO

H3N CH2 COOH CH2 COOH2N

CH2 COOH3N

:OH

H2O

HCl HCl

strong acidpure water

weak acidbuffer solution

NaOH NaOH

strong base weak basepure water buffer solution

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2. Properties characteristic to the carboxyl group:See acid derivatives amides

3. Properties characteristic to the amino group:It could be acylated

α-amino acids peptide

peptide bond

N-terminal (aminoend of the chain)

C-terminal (carboxyl end of the chain)

polypeptide (proteine)(Q might mean any group among the twenty groups)

Preparation of α-amino acids:1. Isolation from hydrolysed proteine or from fermentated solution,e.g., lysine (Lys) is isolated from molasses of sugar factory

nCH CO NH CH CO NH CH COOH

QQQH2N


H2N CH CO NH CH COOHR2R1

-H2OH2N CH

R2COOHH2N CH

R1COOH +

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2. Chemical synthesis

From halogenated carboxylic acid by ammonia

glycineGabriel’s synthesis

glycine

Cl CH2 COOH + NH3 H2N CH2 COOH + NH4Cl

+

H2O120 oC

H2SO4

NH

O

O

K2CO3NK

O

O-KCl

NCH2COOHO

O

C

C

O

O

OHOHH3NCH2COOH

NaOH

Cl CH2 COOH

H3NCH2COO


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Strecker’s synthesis from aldehyde

DL-phenylalanine

From diethyl malonate

diethyl malonate

„malonester”

isonitrosomalonester

acetaminomalonester

CH2 CO

H

NH4CN

-H2OCH2 CH

CN

NH2

HH2O

CH2 CH COOHNH2

COOC2H5

CH3CO NH CHCOOC2H5

HO N CCOOC2H5

COOC2H5

H2/Pd(CH3CO)2O

NaNO2

AcOHCOOC2H5

CH2

COOC2H5


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- CO2OH

NH2

O

HOtyrosine

NH2

HOtyramine

H

NH2N

N

histamineH

OH

NH2

O

N

Nhistidine

- CO2

- CO2

tryptophane

OH

NH2

O

NH tryptamine

NH2

NH

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1. α-Oxoacids

2. β-Oxoacids

Oxocarboxylic acids

COOH

O

H

COOH

O

CH3

CH3

C

O

CH2

C

O

OH OHC

O

CH2

C

O

OH


malonic acid(analogous dicarboxylic acid)

acetoacetic acid

glyoxylic acid pyruvic acid

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Reactions of CH acids

Relatively high acidity (due to the presence of strongly electron withdrawing groups)

CH3 C

O

CH

H

C

O

OEt EtO C CH C OEt

OHOpKa values:

CH3 C

O

CH

H

C

O

CH3

acetylacetone9

ethyl acetoacetate11

diethyl malonate13

H H C:Z1

Z2CZ1

HZ2

H

Z2Z1, = COOEt

COCH3 ,,

C N, NO2

( COOH )


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Reactions of CH acids

Z2 Z2C

H

H

H

Z1

CZ2

R

R Xbase catalysis

alkylatione.g., syntheses by diethylmalonate or by ethylacetoacetate

CO

HR

CZ2

CHR

alkenylation(for oxocompounds)

Z1

CHBrZ1

Z1

base catalysis

Br2


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Carbonyl group containing compoundsOxo-compounds (aldehydes, ketonons)Carboxylic acids and carboxylic acid derivativesSubstituted carboxylic acids and derivatives

Carbonic acid derivatives:two heteroatom attached to the carbonyl group

Carbonic acid derivatives


2011.09.14.. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 98

C

O

Cl ClC

O

Cl ORC

O

RO ORC

O

Cl OH

phosgene(metacarbonic acid

dichloride)

alkyl (aryl)carbono-chloridate

dialkyl carbonate

(chloroformic acid, it does not have

lifetime)

acid chloride acid chloride ester ester ester

C

O

H2N NH2C

O

H2N ORC

O

H2N OHC

O

H2N OM

ureacarbamic acid

(can be decomposed easily)

alkyl carbamate(urethane)

metal carbamate

acid amide acid amide acid amide ester acid amide salt


2011.09.14.. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 99

C O + Cl2,O’, hν, or

activated charcoal 200°C

Cl C

O

Cl

CCl4fumingH2SO4

CHCl3,O’, hν


peter pazmany catholic university · raspberry ketone. lily-of-the-valley aldehyde. organic and...

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