WORLD OF MOLECULES

(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)

Chemical reaction types, energy involvement; reactivity and stability

semmelweis-egyetem.hu

(A kémiai reakciók és típusaik, energiaviszonyaik;

reaktivitás és stabilitás)

WORLD OF MOLECULES

(Molekulák Világa )

Compiled by dr. Péter Mátyus

with contribution by dr. Gábor Krajsovszky

Formatted by dr. Balázs Balogh

(3)

Classification of reactions

1. Acid-base reactions

2. Transformation of functional groups 3. Generation of new carbon-carbon bonds

Ad. 2.

- Electrophilic addition - Electrophilic substitution - Nucleophilic addition - Nucleophilic substitution - Elimination

- Reduction - Oxidation

(5)

According to the attacking agent:

nucleophile N electrophile E

radical R

Kinetical order ≠ molecularity!

(although accidentally it might be)

From a kinetical point of views - molecularity bimolecular (polymolecular)

monomolecular (or unimolecular)

How many molecules construct the activated complex.

Substitution reactions Elimination reactions Addition reactions

Classification of reactions

(6)

Main types

Types: according to INGOLD Substitution

S_N1 , S_N2 S_E1 , S_E2 Elimination

E1 , E2 , E1cb Addition

Ad_N, Ad_E , Ad_R

Ad – addition S – subtitution E – elimination N – nuclephilic E – electophilic

cb – conjugate Base 1 – unimolecular 2 – bimolecular

electrophile (or electrophilic reagent) is a reagent

that forms a bond to its reaction partner (the nucleophile ) by accepting both bonding electrons from that reaction partner

(7)

X –Y formation of a new covalent bond

1. X: + Y nucleophile/electrophile 2. Y: + X nucleophile/electrophile 3. Y· + X· radical

An electrophile (or electrophilic reagent) is a reagent that forms a bond to its reaction partner (the nucleophile ) by accepting both bonding electrons from that reaction partner A nucleophile (or nucleophilic reagent) is a reagent that forms a bond to its reaction partner (the electrophile) by donating both bonding electrons.

Radical (or free radical) is a molecular entity possessing an unpaired electron. In a radical reaction, the reaction may occur between a radical and a non-radical, or between two

(8)

Electrophilic and nucleophilic reagents

The most organic chemical reactions take place between an electron-rich and an electron-poor partner.

Nucleophile Electrophile

Nucleophilic center Electrophilic center Reaction: nucleophilic - electrophilic centers

Mechanism:

is dealing with the electrons taking part in the formation (or cleavage) of the bond. The story of the reaction.

Curved arrows are used for drawings.

(9)

δ⁺

δ⁺ δ⁺

Electrophilic center

δ ^– Nucleophilic

center

δ ^– Electrophilic

center Nucleophilic center

H O I

CH CH₂ CH₃

H O

H

C H H

H

O N O

H

₃

C I

(10)

Drawing mechanism = curved arrow shows the electron movement starting on the electron source

- pointing to the centre of the new bond (in case of bond formation) - pointing to the corresponding atom (in case of lone electron pair

formation)

HO C Br

H H

₃

CH

C HO

H CH

₃

H

+ Br

H

₃

C C O

O H

H

₃

C C O

O + O H H

(11)

H Cl H Cl H

₃

N H H

₄

N

H₃N CH₃

H₃N CH₃ Cl Cl

Examples: bond breaking

bond making

both

Br Br

Br ^light Br

energy

Curly arrows and fishhooks are the conventional ways of depicting electron movements for pairs of electrons and single electron respectively.

(12)

Reagent types:

Ionic reagents - electrophilic, nucleophilic reagents neutral reagents - free radical - radical

Gas phase: Morse potential

homolysis heterolysis

E

ζ

A + B A + B A B

A + B

A + B

(13)

C 2.5

H 2.1

Li 1.0

K 0.8

Na 0.9

N 3.0

O 3.5

F 4.0

Cl 3.0 Br 2.8

= 1 - e -1/4[ Δ (EN)]

δ |

|

Ionic character:

EN = f (IP + EA)

2 f ~ 1/2

(14)

Electronegativity of groups

(H=2.176)

CH₃− 2.473 CCl₃− 2.666

CH₃CH₂− 2.482 C₆H₅− 2.717

CH₂Cl− 2.538 CF₃− 2.985

CHCl₂− 2.602 CN− 3.208

CBr₃− 2.561 NO₂− 3.421

(15)

μ = δ r NaCl

Δ(E

_N

) = 3.0 - 0.9 = 2.1 C-Cl

Δ(E

_N

) = 3.0 - 2.5 = 0.5

dipole moment (polarity of bonds)

C δ+ Cl δ- r

(16)

μ = Q x r

e

^-

= 1,6 x 10

^-19

Coulomb

1 Debye = 3,336 x 10

^-30

C m Debye = D

Coulomb = C

Dipole moment is a vector quantity, the vector product of which with the electric field strength, E, of a homogeneous

field is equal to the torque. T = p × E.

The direction of the dipole moment is from the negative to the positive charge.

Debye is a non-SI unit of electric dipole moment. It is equal to the electric dipole moment for two charges of 10 ⁻¹⁰

franklin separated by 1 ångström, D = 10 ⁻¹⁸ Fr cm ≈ 3.335 64 × 10 ⁻³⁰ C m

(17)

0 2 4

50%

Δ (EN) 0.0

1.0 δ

NaCl

C - Cl

(18)

Arrange the following reagents: are they electrophile, nucleophile, or radical?

H₂O AlCl₃ BF₃ ROH

A/ B/ C/ D/ E/ F/ G/ H/

HO RS RO CN

NH₃

I/ J/ K/ L/ M/ N/ O/ P/ Q/

NO₂

(CH₃)₃C NO₂ CH₃ Cl Br Br H CH₂

R/

Some example and application on several reaction types

(19)

How would you prepare the following alkenes from dibromoethane?

What is the stereochemical requirement of the reaction?

C C H

Ph

Br Ph

C C

Ph Br H

Ph

(20)

A/ Give the products of the following reactions!

B/ What is the molecularity and kinetics of them?

II/ C C

H

Br R₃

R₄

R₂

R₁ boiling

HO / H₂O

I/ C

CH₃ H₃C

CH₃

Cl NaI aceton boiling

(21)

What is the product of the following reactions? Determine stereochemistry.

CH

₃

CH

₃

Br

₂

/ CCl

₄

KMnO

₄

/ H

₂

O

(22)

What are the products of the following reactions:

CH₃

F CH₃ Br₂

FeBr₃

A + B

C

CH CH₂

Br₂ E D

CH(CH₃)₂

G

CH₃

H

3 Cl₂

hν I

NBS

CH₂CH₃

NBS CCl₄ CCl₄

KMnO₄ / H₂O reflux majd H

NBS: N

O

Br hν

hν

then

(23)

Prepare the following compounds from naphthalene:

CN CH₂CH₂CH₃ Br

A/ B/ C/ Br

(24)

Alkylation of benzene (S_EAr)

kinetically controlled reaction condition: ortho and para products thermodinamically controlled conditions: metha product

CH₃ H

H H₃C

CH₃ H H

CH₃ +CH₃, -CH₃

+CH₃, -CH₃ CH₃

H₃C

-H CH₃

CH₃Cl AlCl₃

CH₃

CH₃ CH₃Cl

AlCl₃ +

CH₃

+H +H

CH₃

CH₃ H

H

CH₃

CH₃ H H

H CH₃ H CH₃

CH₃ H₃C

(25)

SO₂OH

H₂SO₄ -H +H

H SO₂OH

+H

H H

SO₂OH +SO₂OH

-SO₂OH SO₂OH

-H

H H

SO₂OH

Sulfonation of naphtalene

kinetically controlled: α product

thermodinamically controlled: β product

(26)

Diels-Alder reactions

concerted, stereospecific reaction, cis addition on both component

XH X H X H HX

HX HX HX XH

m m

X = -COOCH₃

C C X

H

H X

C C X

H

X H

HX HX

180^o

HX X H

180^o

enantiomers achiral, same compounds

(27)

S_N2 reaction route - linear transition state, configuration inversion S_E2 reaction route - cyclic transition state, configuration retention

WORLD OF MOLECULES

Chemical reaction types, energy involvement; reactivity and stability

WORLD OF MOLECULES

Compiled by dr. Péter Mátyus

with contribution by dr. Gábor Krajsovszky

Formatted by dr. Balázs Balogh

Table of Contents

Classification of reactions

Classification of reactions

Main types

X –Y formation of a new covalent bond

1. X: + Y nucleophile/electrophile 2. Y: + X nucleophile/electrophile 3. Y· + X· radical

Electrophilic and nucleophilic reagents

Mechanism:

H O I

H O

H

C H H

H

O N O

H

C I

HO C Br

H H

CH

C HO

H CH

H

+ Br

H

C C O

O H

O H

H

C C O

O + O H H

H Cl H Cl H

N H H

N

Curly arrows and fishhooks are the conventional ways of depicting electron movements for pairs of electrons and single electron respectively.

Reagent types:

Gas phase: Morse potential

A + B A + B A B

A + B

C 2.5

H 2.1

Li 1.0

K 0.8

Na 0.9

N 3.0

O 3.5

F 4.0

Cl 3.0 Br 2.8

= 1 - e -1/4[ Δ (EN)]

δ |

|

Ionic character:

EN = f (IP + EA)

2 f ~ 1/2

Electronegativity of groups

μ = δ r NaCl

Δ(E

) = 3.0 - 0.9 = 2.1 C-Cl

Δ(E

) = 3.0 - 2.5 = 0.5

dipole moment (polarity of bonds)

C δ+ Cl δ- r

μ = Q x r

e

= 1,6 x 10

Coulomb

1 Debye = 3,336 x 10

C m Debye = D

Coulomb = C

0 2 4

50%

Δ (EN) 0.0

1.0 δ

NaCl

C - Cl