Carbonyl compounds

(1)

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

Consortium leader

PETER PAZMANY CATHOLIC UNIVERSITY

Consortium 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 UNIVERSITY SEMMELWEIS

UNIVERSITY

(2)

Carbonyl compounds

(Karbonilcsoportot tartalmazó vegyületek)

Organic and Biochemistry

(Szerves és Biokémia )

semmelweis-egyetem.hu

Compiled by dr. Péter Mátyus

with contribution by dr. Gábor Krajsovszky

(3)

Organic and Biochemistry: Carbonyl compounds

Carbonyl compounds

C O containing carbonyl group (carbon-oxygen double bond)

I. Aldehydes a -CHO group is connected to a C-atom

a) substitutive name (IUPAC name) as a prefix: formyl

as a suffix: -al, carbaldehyde

CH₃ CH₂ CH₂ CHO OCH CH⁵ ⁴ ₂ CH CH CHO³ ² ¹

butanal pent-2-enedial

OCH CH₂ CH CH₂ CH₂ CHO CH₂ CHO

1 2 3 4 5 6 CHO

3-formylmethylhexanedial cyclohexanecarbaldehyde

b) common names

(6)

Aldehyde Carboxylic acid

H C O

H

H C O OH

C O

H

CH₃ _CH₃ _C ^O

OH

C₂H₅ C O H

C

OH O C₂H₅

O O

formaldehyde

acetaldehyde

propionaldehyde

a. formicum formic acid a. aceticum acetic acid

a. propionicum propionic acid a. butyricum Organic and Biochemistry: Carbonyl compounds

(7)

Aldehyde Common names Carboxylic acid

i-C₃H₇ C O

H isobutyraldehyde C O

OH C₃H₇

i- a. isobutyricum

isobutyric acid

C₄H₉ C O H

valeraldehyde ^C4H₉ ^C O OH

a. valerianicum valeric acid

HO CH₂ C O

H

glycolaldehyde _HO _CH₂ _C ^O

OH

a. glycolicum glycolic acid

C H

CH₂ CH₂ C

O O

H

succinaldehyde ^O _C

HO

CH₂ CH₂ C O OH

a. succinicum succinic acid

C O

H benzaldehyde ^C ^OH

O

a. benzoicum benzoic acid Organic and Biochemistry: Carbonyl compounds

(8)

CHO

OCH₃ HO

COOH

OCH₃ HO

vanillin

CHO

O O

COOH

O O

piperonal

piperonylic acid

HO

OH

CHO

protocatechualdehyde

COOH HO

OH

(9)

Aldehyde Carboxylic acid

CHO OH

COOH OH

H₃CO

CHO _COOH

H₃CO

CHO H₃CO

COOH

H CO

salicylaldehyde salicylic acid

p-anisaldehyde

veratraldehyde

p-anisic acid

veratric acid Organic and Biochemistry: Carbonyl compounds

(10)

II. Ketones containing a carbonyl group with two R groups.

within a chain C O

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 5

CH₃ C CH₂ COOH O

4 3 2 1

H₂C CH CH₂ C CH₃ O

2 1 3

5 4 O

1-chloro-2-methylpentan-3-one 3-oxobutyric acid Organic and Biochemistry: Carbonyl compounds

(11)

b) radicofunctional

H₃C C CH₂CH₃ O

ketone

ethyl methyl ketone c) aromatic ketones

C O

CH₃ acetyl → acetophenone

C O

benzoyl → benzophenone Organic and Biochemistry: Carbonyl compounds

(12)

Synthesis

1. Methods for preparation of both aldehydes and ketones - Oxidation

Jones reagent: H₂CrO₄ • H₂SO₄ (water-acetone) Collins reagent: CrO₃ • pyridine

MnO₂ active (← KMnO₄ + MnSO₄)

(13)

- By hydration of acetylenes

2. Syntheses of aldehydes

a) By reduction of carboxylic acid derivatives - From acid chlorides: Rosenmund reaction

R C CH H₂SO₄ R C CH₂

OH R C

O

CH₃ Hg²⁺- salt

enol

(14)

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

H

CHO

C CH₃ CH₃

HO H

(15)

I. Addition reactions II. Enolate chemistry III. Oxidation-Reduction

Reactions of aldehydes and ketones

(16)

Reactions of carbonyl compounds

1. Nucleophilic addition to the carbonyl group under basic conditions:

Nu C O Nu C

O

Nu C

δ+ δ− H⁺ OH

tetrahedral intermediate under acidic conditions:

C OH H⁺ Nu

C O

H H

C O

(17)

2. Reaction of the α carbon atom

enolate / enol formation → electrophilic substitution on the α carbon

by base catalysis: → enolate anion

B O O

E⁺

E O

O

H

by acid catalysis: → enol

E OH O

H OH H⁺

O

(18)

I. Addition and condensation reactions

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

tetrahedral intermediate - H₂O product a) Addition of water

b) Addition of alcohol Step 1.

CH₃ CH₂ C O

H ⁺ H₂O CH₃ CH₂ C OH HOH

CH C O H OH CH₃OH OH

aldehyde hydrate

(19)

Step 2.

‘acetal’

CH₃OH

H₃C C

OCH₃ H

-H H₃C C

OCH₃ OCH₃ H

CH₃ C

OH H

OCH₃ H

CH₃C

OH₂ H

OCH₃-H₂O

CH₃ C OCH₃ H

Step 1. (with base catalysis)

hemiacetal

CH₃ C OH H

OCH₃ -H

CH₃ C H O H

OCH₃ O CH₃

CH₃ C O H

(20)

c) Addition of sodium hydrogen sulfite

R C O

R' R C

OH SO₃ R'

Na H

R C O

R'

R’ = H, alkyl

aromatic aldehydes ± aromatic ketones –

adduct

d) Addition of HCN C

R R^'

O C

R R^'

CN OH HCN

( B)

CN

(if R=Ar, R’=H)

ArCOAr : does not react!

cyanohydrine Organic and Biochemistry: Carbonyl compounds

(21)

acyloin benzoin condensation

(22)

e) Wittig reaction → see preparation of olefines f) Addition of acetylenes → see acetylenes

g) Addition of Grignard compound → see preparation of alcohols Note: side reactions are possible in the following cases

a) with a sterically hindered ketone → enolisation

C H

C O

R R'MgX

R'H + C C R O

H⁺

b) with a sterically hindered Grignard compound → reduction

C H

H O H

(23)

h) Reduction by metal hydrides → see alcohols

(24)

i) Reaction of amines

- NH₃

O

NH₂

OH NH

hemiaminal imine - RNH₂

O N-R

Schiff's base

- R₂NH CH O

CH C NR₂

OH

C NR₂ C

enamine - R₃N

O

C NR₃X

OH

(25)

A = HO - hydroxilamine OXIME

A = NH₂ - hydrazine HYDRAZONE

A = semicarbazide SEMICARBAZONE

j) Aldol reaction

A - NH₂

O N-A

+

C C R¹

R²

C O

R OH

C C H O

R C R² R¹

R¹ C R² O C C

O R

H₂N C NH O

(26)

H

₂

C C O

H H

H

₂

C C O

CH

₃

H

₂

C C O

OC

₂

H

₅

H

pK

_a

17 19 24

(27)

Reactions of α,β-unsaturated carbonyl compounds

O

Nu HNu

O Nu H

Nu

OH

'1,4 - Addition'

and / or

'1,2 - Addition'

1 2 3

4

(28)

Aspects of regio- and stereoselectivity

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

strongly basic nucleophiles → 1,2 weakly basic nucleophiles → 1,4

(29)

II. Reactions through enolate anion

Oxo-enol tautomerisation

CH

₃

C CH

₃

O CH

₃

C

OH

CH

₂

oxo enol

CH

₃

C O

CH

₂

C O

CH

₃

O CH

₃

C

O H

CH C CH

₃

16 % 84 %

10

^-4

%

(30)

H C

CH₂

allyl anion enolate anion H C

O CH₂

H C O CH₂ H C

CH₂ CH₂ H C

CH₂ CH₂

H C O CH₂

(31)

Electrophilic substitution

O

1. LiNPr₂ 2. CH₃I

O

CH₃ pK_a = 17

-70°C OLi

i

CH₃I

-70°C

pK_a = 40 LiNPr₂i

H₃C

H₃C NH 2 CH

(32)

R C O

CH₃

X₂

acid R C

O

CH₂ X

Halogenation at the α-position

R C O

CH₃ R C

O

CH₂

B^- I I

R C O

CH₂ I

δ+

δ−

R C δ+

O

CH₂ I B^-

R C O

CH I

I₂

R C O

CHI₂

O O O

(33)

Disproportionation

Cannizzaro reaction

Aldehydes without α-H carboxylic HO acid + alcohol

R C H

O OH

R C H OH

O

C

H R

O

R C O

H R C

O

RCH₂OH Organic and Biochemistry: Carbonyl compounds

(34)

Oxidation-reduction

Reduction

- Kizsnyer-Wolff

see paraffins - Clemmensen

see paraffins

- metal hydrides (Meerwein-Ponndorf-Verley)

see nuclephilic addition (hydride) see alcohols

(35)

Oxidation

R-CHO R-COOH O₂/peracids H₂O₂

KMnO₄ O

HNO₃

HOOC (CH₂)₄ COOH

Ph C CH₃ SeO₂

Ph C CHO O

RCO₃H O

O

(Baeyer-Williger) Organic and Biochemistry: Carbonyl compounds

(36)

Some important aldehydes:

Formaldehyde: Its 40% aqueous solution is formalin

Acetaldehyde

O

O O

O H

H₃C

H CH₃ H CH₃

H CH₃

H₂SO₄

H₂SO₄ HCl

H₂SO₄, H₃C

O O

O

H H

H H₃C

CH₃

Paraldehyde

Metaldehyde Organic and Biochemistry: Carbonyl compounds

n = 10 - 100 parafor maldehyde

n HOCH₂OH HO(CH₂ O)n-1CH₂OH

(37)

Carboxylic acids and carboxylic acid derivatives

H C

O

O H

1.2

125^° 111^° 1.34

124^°

Carboxylic acids: compounds containing

C O

OH

group R C

O

acyl group

(38)

Carboxylic acid derivatives:

Z: heteroatom, or group

Z: halogen → acid halide acyloxy → acid anhydride alkyl/aryloxy → ester

NR¹R² → carboxamide

→ nitrile

→ imidate meaning of

(39)

C

O OH

Carboxylic acid

C

O

O OH Peroxy acid

(40)

C

Cl

O O OH O

OOH

O

2

Mg

m-chloroperoxybenzoic acid magnesium monoperoxyphthalate Organic and Biochemistry: Carbonyl compounds

(41)

C

O OH

C

OH OH

OH

carboxylic acid orthocarboxylic acid

C

O OR

C

OR OR

OR

(42)

Imid-, hydrazon-, hydroxime- and hydroxamic acid Tiocarboxylic acid

(43)

1. Classification of carboxylic acids

monocarboxylic acid

dicarboxylic 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

C

H₃ COOH HOOC COOH HOOC CH₂ COOH

1,2 1,3

CH₂ COOH C

H₃ H₂C CH COOH

(44)

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 COOH C

H₃

HOOC CH CH₃

CH C OH O

COOH

cyclohexanecarboxylic acid

COOH

(45)

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

(46)

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

(47)

c) Unsaturated carboxylic acids:

acrylic acid acryloyl

propiolic acid propioloyl

crotonic acid crotonyl

isocrotonic acid isocrotonyl Organic and Biochemistry: Carbonyl compounds

C

H₂ CH COOH

C

H C COOH

C C C

H₃

COOH H

H

C C

H H

(48)

(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

butenedioic acid fumaric acid fumaroyl

oleic acid oleoyl Organic and Biochemistry: Carbonyl compounds

C H₃

O

OH C C (CH₂)₇

(CH₂)₇

H H C

H₃ COOH

(49)

d) Aromatic carboxylic acids

benzoic acid benzoyl

naphthoic acid naphthoyl

phthalic acid phthaloyl

isophthalic acid terephthalic acid

COOH COOH

COOH

(50)

Acidic residue:

carboxylic acid → carboxylate 3. Preparation of carboxylic acids

a) Preparative methods - Oxidation

from alcohols from aldehydes from ketones

R C

O^- O

NO₂

CH₃

NO₂

COOH KMnO₄

(51)

- From organometallic compounds

- From nitriles

C

H₃ CH₂ CH CH₃ MgBr

CO₂

C

H₃ CH₂ CH CH₃ CO₂MgBr

C

H₃ CH₂ CH CH₃ COOH H⁺

Li COOH

CO₂

H⁺

R X KCN

R CN

H₃O⁺

R COOH

(52)

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

(53)

Acid halides

Nomenclature: acyl group + halide

CH

₃

C O

Cl

C O Br

CH

₂

C O Br

(54)

COOH

C O Cl

3-(chloroformyl)cyclohexanecarboxylic acid

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

Cl S O

Cl R C SO₂

O Cl O SOCl

+

R C O

+ -HCl R C

O OH

+

COOH PBr₃

3 3 C

O Br

+ H₃PO₃

HX O

(55)

Preparation of acid fluorides:

Preparation of acid anhydrides:

R C O OH

R C O O C

O R ,

Nomenclature:

acid acid anhydride

C O O H C C

H₃C

acetic anhydride

C O

O CH C

H₃C CH

acetic propionic anhydride

(56)

Preparation:

,

R C

O O C R

R COO +

,

R COCl Mixed anhydrides:

(57)

Esters:

Nomenclature

methyl acetate

H

₃

C C O

O CH

₃

CH

₂

C O

OCH C

O

Na

(58)

ethyl (2-methoxycarbonyl- phenyl)acetate

By traditional nomenclature:

benzoic acid ethyl ester

Orthoesters: esters of the (hypothetic) ortho acids

triethyl orthoacetate

(59)

Preparation

CH

₃

C O

OH

CH

₃

OH/H

CH

₃

C O

OCH

₃

CH

₃

C

O Z

HOR CH

₃

C O

acid anhydride

OR

acid halogenide

CH

₃

C O

OCH

₃

ROH/RO v. H

CH

₃

C O

OR CH

₃

C

O R X ,

CH

₃

C O

,

(60)

Acid amides

1^o order

(61)

Nomenclature

Primary amides: ‘ acid + amide’ → acid amide

‘carboxylic acid + amide’ → carboxamide

cyclohexanecarboxamide Analogous name:

But: acetamide H₃CCONH₂

benzamide C₆H₅CONH₂

succinamidic acidH₂NOC(CH₂)₂COOH

(62)

as acyl-amino group

4-(acetylamino)benzoic acid

4-(N-methylcyclohexyl- carbonylamino)benzoic acid

But:

(63)

Preparation:

By acylation of amines:

By heating of ammonium carboxylates:

By hydrolysis of nitriles:

(64)

Acid nitriles:

R C O OH

R C N

Nomenclature

• hydrocarbon + nitrile

CH

₃

(CH

₂

)

₄

C N

hexanenitrile

N C (CH₂)₄ C N hexanedinitrile

• carboxylic acid → carbonitrile CN

cyclohexanecarbonitrile

• trivial: acid → onitrile

(65)

Preparation:

Imide esters:

R C O NH₂

- H₂O e.g., P₂O₅ SOCl₂/DMF

R C N

R CH N OH - H₂O

Ac₂O R C N

R X ⁺ NaCN R C N

R C N :C N R

isonitrile

nitrile

nitrile conditionsPTC

DMF

or DMSO

R OH, NH

(66)

Physical properties

Monocarboxylic acids: are liquids up to C₈

their 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)

(67)

Chemical properties of acid derivatives

1. Acidity:

carboxylic acids >> alcohols, but <<mineral acids pK_a

HCl CH₃COOH

CH₃CH₂OH

pK_a -7

4.76 16

1.27 /4.27 2.85 / 5.70

HOOC COOH HOOC CH₂ COOH

carboxylic acid amides pK_a ∼ 15

CH₃ C O ^CH₃ ^C ^OH pK_a ∼ 0

NH₂

(68)

2. Reactivity against nucleophiles

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

R C O R

,

Nu + X

R C O elimination

X R O C

addition Nu X

Nu: C O R

c.p. with aldehydes / ketones

(69)

The reactivity mainly depends on two opposite effects:

1. The greater is the -I effect of X, the higher the electrophilicity of 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

>

X

C O δ-

2δ+ δ-

C O

X

(70)

a) Acid halides

-I effect of the halogen atom is dominating b) Esters and amides

Their reactivity is decreased by delocalization

Acylation reactions

H atom is replaced by an acyl group

O, S, N, C acylation

H-Z

acylating agent

R C O Z

(71)

Some important reactions of carboxylic acids and its derivatives

a) Carboxylic acids Decarboxylation:

R C O

O Na

NaOH R H Na

₂

CO

₃

Δ

C O O

-CO

₂

C O

HO CH C O H

O -CO C CH₂ CH₃COOH HO

Δ HO

(72)

b) Acid halides:

Preparation of acid azide

Schotten - Baumann acylation

NaN

₃

R C O

X R C O

N

₃

NaOH water Ar C O

Cl R

²

R

¹

NH Ar C

O

N R

¹

R

²

(73)

c) Esters:

Preparation of hydroxamic acid

Preparation of acid hydrazide

H

₂

NOH R

NH OH C

O R C

O

OR' R

^'

OH

NH

₂

NH

₂

R C

O OR'

R C O

NHNH

₂

R'OH

(74)

R C O Y

R`MgX R

C R`

OMgX Y

R C R`

O

R`MgX

C OMgX R

R`

Y = OR``, Cl, Br

Preparation of tert-alcohol

(75)

d) Acid amides:

Reaction with nitrous acid

HNO

₂

-H

₂

O N

₂

R C O NH

₂

R C O OH

-H

₂

O HNO

₂

R C O

N R

^,

NO R C

O NHR

^,

(76)

R CN HCl

C₂H₅OH ^R ^C

NH.HCl OC₂H₅

2 C₂H₅OH

R C

OC₂H₅ OC₂H₅ OC₂H₅ Imidic acid ester

hydrochloride

Preparation of orthoesters

(77)

Substituted acids

Halo acids Hydroxy acids Amino acids Oxo acids Halo acids

R contains halogen

Nomenclature: halogen as prefix

3-bromopropionic acid 2-chlorocyclohexanecarboxylic acid

R COOH

BrCH

³ ₂

CH

² ₂

COOH

¹

COOH Cl

(78)

Preparation:

α-halogenated carboxylic acids 1. Hell-Vollhardt-Zelinsky

R-CH₂-COOH + PX₃ R-CH₂COX enol

oxo R CH C OH Cl

R CH

Cl C OH

Cl

Cl Cl Cl

R CH

Cl C O

Cl+ HCl 2 P ⁺ 3 X₂ 2 PX₃

(79)

2. From hydroxy acids:

R CH COOH HBr OH

R CH Cl

C O Cl H

₂

O R CH COOH

Br

R CH COOH Cl

SOCl

₂

(80)

Chemical properties

Reaction with base (NaOH)

R-CH

₂

-CH

₂

-CH-COOH Cl

γ β α

RCH

₂

CH

₂

CH-COOH α-hydroxy acid OH

β α

γ

RCH

₂

-CH= CH-COOH

α,β - unsaturated acid R CH

₂

CH CH COOH

Cl H

R-CH-CH

₂

-CH

₂

-COOH Cl

γ

R O O

γ - lactone 4-butanolide

δ

(81)

O

O O

O O O O

β α γ

δ

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

N

O

H

N O

H N O

H

γ β α

N O H

δ

α-lactam β-lactam γ-lactam δ-lactam

Lactones (cyclic esters) and lactams (cyclic amides)

(82)

Hydroxy carboxylic acids

- Nomenclature

* hydroxy as prefix

* trivial names Ph-CH-COOH

OH HOOC-CH₂-C-CH₂COOH COOH

OH

HO-CH₂-COOH

mandelic acid citric acid glycolic acid

H₃C-CH-COOH OH

HOOC-CH-CH₂-COOH

OH OH

HOOC-CH-CH-COOH OH

lactic acid malic acid tartaric acid

(83)

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-COOH

Cl OH

H₃C C OH H H₂O COOH

H₃C C H OH H

CN H₃C C O HCN

H

Br CH₂COOC₂H₅ Zn H₃C

C H₃C

H₃C CH₂ COOH HO

β α

(84)

Amino acids

(85)

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 acid

diamino monocarboxylic acid

monoamino dicarboxylic acid, etc.

- according to the structure of the carbon chain

NH

₂

, NH , N , N

C O OH

(86)

Open-chained, aliphatic, monoamino monocarboxylic acids

Aminoacetic acid Aminoethanoic acid Glycine

α-aminopropionic acid 2-aminopropanoic acid Alanine

β-aminopropionic acid 3-aminopropanoic acid β-alanine

ε-aminocaproic acid 6-aminohexanoic acid ω-amino acids

H

₂

N CH

₂

COOH H

₃

C CH COOH

NH

₂

H

₂

N CH

₂

CH

₂

COOH H

₂

N (CH

₂

)

₅

COOH

(87)

Amino acids in proteins

Glycine (Gly) G Proline (Pro) P

R = CH₃

Alanine

(Ala) A Valine

(Val) V

Leucine

(Leu) L Isoleucine

(Ile) I

Methionine

(Met) M Phenylalanine

(Phe) F

Serine

(Ser) S Cysteine

(Cys) C Threonine

H

₂

N-CH

₂

-COOH ^N

H COOH R H

H

₂

N COOH

amino acids

substituted on the α-C

CH

₃

CH

₃

CH

₃

CH

₃

CH

₃

CH

₃

S CH

₃

OH SH

CH

₃

(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

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

OH

N H

N NH ₂ O

NH ₂

O OH

O ^OH

O

NH ₃

N NH

₂

NH

₂

(89)

Chemical properties

1. Acid-base character

„aminoacetic acid”

practically does not exist

glycine

„zwitterionic system”

weak acid

weak base Buffer effect of glycine

H N

CH₂ C O

H OH N

H

CH₂ H

H C O

O Organic and Biochemistry: Carbonyl compounds

H₂O H₃O

H₃N CH₂ COO

H₃N CH₂ COOH H₂N CH₂ COO CH₂ COO H₃N

:OH H₂O

HCl HCl NaOH NaOH

str ong base weak base

(90)

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 (amino end 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:

CH CO NH CH CO NH CH COOHn Q Q

Q H₂N

H₂N CH CO NH CH COOH R²

R¹ -H₂O

H₂N CH R² H₂N CH COOH

R¹

COOH ⁺

Carbonyl compounds

Carbonyl compounds

Organic and Biochemistry

Compiled by dr. Péter Mátyus

with contribution by dr. Gábor Krajsovszky

Table of Contents

Table of Contents

Carbonyl compounds

I. Aldehydes a -CHO group is connected to a C-atom

Aldehyde Carboxylic acid

II. Ketones containing a carbonyl group with two R groups.

Synthesis

Reactions of aldehydes and ketones

Reactions of carbonyl compounds

I. Addition and condensation reactions

H

C C O

H H

H

C C O

CH

H

H

C C O

OC

H

H

pK

17 19 24

Reactions of α,β-unsaturated carbonyl compounds

O

Nu HNu

O Nu H

Nu

OH

'1,4 - Addition'

and / or

'1,2 - Addition'

Aspects of regio- and stereoselectivity

II. Reactions through enolate anion

CH

C CH

O CH

C

OH

CH

oxo enol

CH

C O

CH

C O

CH

O CH

C

O H

CH C CH

16 % 84 %

10

%

Electrophilic substitution

Halogenation at the α-position

Disproportionation

Oxidation-reduction

Oxidation

Carboxylic acids and carboxylic acid derivatives

H C

O

O H

C O

OH

group R C

O

acyl group

C

O OH

Carboxylic acid

C

O

O OH Peroxy acid

C