Compui heterociclici Compui heterociclici triatomicxi i tetraatomici cu un heteroatom

O oxirane O oxirne O oxtane O oxte

S S S thiairane thiairne thietane

S thite

N N H H aziridine azirine

NH aztidine

N azte

Compui heterociclici pentaatomici cu un heteroatom

O furanne S thiophne N H pyrrole

.. A
.. A = .. O .. , .. S .. , .. N H ,

.. C H
.. N R , .. N ..

.. .. A A
+

.. .. A
+

A
+

..

A
+

O O benzo[b]furanne isobenzofuranne O dibenzofuranne O THF

S S benzo[b]thiophne benzo[c]thiophne S 2,5-dihydrothiophne S thiolane

NH N H indole isoindole N H carbazole N H 2-pyrroline N H pyrrolidine

Metode de obinere
CH2 CH2 C=O H3 C C : CH3 O .. P 2 O5 H3 C O OH CH3 -H2O H3C O CH3

CH2 CH2 P 2 S5 H 3C C C=O H 3C O CH3

CH2 CH2 C=O C : CH3 S ..

H 3C

OH CH3 -H O H3C 2

CH3

CH2 CH2 NH3 HO H3C C C CH3 H3C O O N H OH CH3 -H2O H3C N H CH3

H2C CH2 HO R NH2 H3C C C CH3 H3 C O O N R OH CH3 -H2O H3C N R CH3

R O NH2 + O COOR' R -H2O R O N COOR' R -H2O R N COOR' R R N H COOR' R

Cl R + O H2 N COOR' R -HCl R O HN COOR' R R COOR' R -H2O

NH2

COOR' -H2O R N R R N H

COOR' R

Proprieti chimice Caracterul acido-bazic

+ KOH N H .. N .. + K+ + H2O

+ CH3MgX N H
.. .. N .. N .. ..

.. N ..

+ MgX+ + CH4

.. N .. N .. ..

N ..

N ..

.. O ..

+ H+ O
+

H H
H2O -H+ CH2 CH2 CH CH O O

.. O ..

+ H+ O
+

OH O H

...

.. N H
+

+ H+
+N

+ H H N H

+ N H
H A
+

Reacii de SE
.. A H E
+

.. A

H E

H .. A
+

H E A
+

N H

+ CH3 COONO2

N H

NO2

+ CH3 COOH

N H

+ SO3

Py N H
Br Br N H Br

SO3H

Br2 N H Br

N H
2

+ (CH3CO)2O

N H
CH2

COCH3

+ CH3COOH

N H

+ CH2=O

FeCl3 N H N H

N H

CH N

N H

+ Ar N=N]X-

N H
H+ N H

N=N Ar

+ HX

CH3Cl/KOH N H

Cl CH=O + N

N H

+ DMFA

POCl3 N H
ZnCl2, HCl

CH=O

N H

+ R C=N

H2O N H

CO R

+ I2

HNO3 S I

+ CH2=O + HCl

CH2 Cl

+ H2 O

Compui heterociclici pentaatomici cu dois au mai muli heteroatomi Azoli Azoli cu doi heteroatomi
N O isoxazole N O 2-isoxazoline NH O 4-isoxazoline NH O isoxazolidine

N O oxazole
N

N O 2-oxazoline

NH O 4-oxazoline
N O benzo[c]isoxazole

NH O oxazolidine
N O benzoxazole

O benzo[d]isoxazole

N N H pyrazole

N N H benzopyrazole

N N H 2-pyrazoline

NH N H 3-pyrazoline

NH N H pyrazolidine

N N H imidazole

N N H benzoimidazole

N N H 2-imidazoline

NH

NH

N N H H 4-imidazoline imidazolidine

N N S isothiazole N S benzo[d]isothiazole N S thiazole NH

N S benzothiazole

N S S 2-isothiazoline 2-thiazoline

S thiazolidine

Obinerea izoxazolului i aderivailor si

CH2 C R R C O -H2O + O NH2 HO CH2 C R R C N HO O R R HO C O N -H2O R O R N

R CH C R R CH O -H2O + NH2 HO R O N + R O R NH

CH2 C R C O O OR' O + NH2 -H2O -R'OH HO R O

CH2 CH2 CH2 X X + NH2 -2HX HO NH

Obinerea oxazolului i a derivailor

R CH2 HONO R C -H2O O R C=N OH Zn+CH COOH R CH NH SOCl2 3 R C C CH3 R C (CH3CO)2O R O O O R N O CH3

R CH NH R' C C R O O R H
+

R N O H -H R 2O R'
+

HO R'

N O R

R'= alkyle, aryle, OR, NR2

NH2 O C R + R C CH2 O X
.. N O

R N -HX/H2O R O

Proprietile bazice i nucleofile ale oxazolilor

+ HA NH O + A-

N: + R I

N R+I

Reaciile SE
N O E+ -H+ E N O ; O E+ N -H+ E O N

Dioazolii i derivaii lor Obinerea pirazolului i a derivailor

CH2 C R R C O -H2O O + NH 2 H2N R R N H N

CH C R R CH O -H2O + NH2 HN R R R N R N [O] R N R R N

CH2 C R C O O OR' O + NH2 -R'OH -H O 2 HN R R N R N

H2C CH2 X H2C X + NH2 -2HX H2N N H NH

R C C R .. + N H2C N
+

.. C=C R N+ H2C N

R N

R N

N H
R N R

R CH=CH R .. + N H2 C N
+

R .. R CH CH N+ H2C N

R NH

Obinerea imidazolului i a derivailor

R R C C O + O NH3 NH3 + O=CH R -3H2O R R N N H R

H2N C + C R -2H2O CH HN OH -HX R (X)

H2C NH2 + O=CH R H2C NH2

R N R N H
NH N H R

Proprietile pirazolilor i ale imidazolilor

N N H H N N N H N N H

R R
5

R
4

N H

NH

NH

N H
NH N+ H

N N H

+ H

NH N H

N H

+ H+
N H

NH

.. N .. N H

+B

.. N -BH+ .. N ..

N+ H .. N:

NH

N ..

.. N: N H

+ B

-BH+
E N H N

.. N: N ..
N N H

N ..

:N:
E N N H E E N N H

N H

E+ N -H+

E+ -H+

Izotiazol, tiazol i derivai Metode de obinere

R NH2 C=O + CH R R C S X

R NH2 C=O R C CH R S

R NH C=OH R C R XS

R HN R S

OH R -H2O R
-HX

R N S R

R R CH NH2 + CS2 CN N H2N

N S R

SH

H2C NH P4S10 R C C R R O O

Proprieti
N S
E S
.. A

+ R X S

N R

+ X-

+ E

-H+
N S

N
N S ..

Azoli cu trei sau mai muli heteroatomi

N N O 1,2,3-oxadiazole (instable)
N N

N N O 1,2,4-oxadiazole N O 1,2,5-oxadiazole N

N N O 1,3,4-oxadiazole

N S 1,2,4-thiadiazole N S 1,2,5-thiadiazole N N

N N S 1,3,4-thiadiazole

S 1,2,3-thiadiazole

N H

N N

NH N

N NH

N N

N NH

1,2,3-triazole

N N H 1,2,4-triazole

N N N N N NH N N H tetrazole

Metode de obinere
R C N C R N OH R t -H2O N O R N

OH

NH NH R C C R O O

t -H2O R

N N O R

NH N R C CH R O (CH3CO)2O -CH3COOH R N N O COCH3 R

NH NH R C C R O O P4S10 t R N N S N N S NH2 R N NH R CH C NH2 -H2O S [O]

N NH -H2O R N R

NH NH H+ R C C NH2 -H2O R O S

NH NH R C C R O O + NH3 N NH C R R C NH2 O

R NH CO R + NH R CO 2 HN R -H2O NH C R N R C -H2O R O NH R N N R N

R CO R NH2 t + NH R C -H2S S NH2

NH NH OHR C C NH2 -H2O O S H+ R

NH2 CO R R C NH -H2O R N
N NH N SH

N N H N

Compui heterociclici hexaatomici Compui heterociclici hexaatomici cu un heteroatom

A .. N .. pyridine O pyrylium S thiinium

N H pipridine

O 2H-pyrane

O 4H-pyrane

O oxane

S 2H-thiine

S 4H-thiine

S thiane

Piridina
+

.. N ..

.. N ..

.. N ..

+ N .. N .. -

Metode de obinere
R C O NH3 C R -2H2O O [O] -H2O

N H
H

R C O

C R O

NH2OH -2H2O

R N OH

-H2O

O OH NH3 -H2O NH OH NH2 O -H2O N

O
+

NH3 -H+

O
+

R NH2

R O NH2

R -H2O

+ NH3 O O C O OH NH2 O C O -H2O NH2 N O N OH

R CH O R COOCH3
NH3 -2H2O

R COOCH3
[O]

H3COOC

CH2 CH2 + C C R O O R

H3COOC R N H

H3COOC R N

COOCH3 R

Proprieti chimice Caracterul bazic

+

+ HA N .. N+ H N H
+

AN H
+

N H

Reacii de alchilare i de acilare

XN+ CO R RCOX N RX N+ R X-

Reacii SE
H E
+

N ..
+

N ..

H E

N ..

H E

trs defavorable
+

H E
+

H E N ..
H E

H E N ..
H E
+

N ..
H E
+

N ..

N .. trs defavorable
+

N ..

Reacii SN
X + Nu:N X Nu .. N .. -XNu

+ Nu:N+ R X

.. N R

X -XNu

N+ R

Nu

NH2 Cl KNH 2 N -HCl N NH3 N + N NH2

+ RLi N ..
HNuMe

.. N .. Li+
.. N .. Me+

H -LiH R

R
MeH H 2O

N ..

H -MeH NuH

N ..

NuH

-H2

Nu:-Me+

-MeOH

NuH

Reacii la catena lateral

CH3 [O] N N COOH

CH3

B -BH+

.. N .. CH2 .. N .. CH2 N CH2 N

.. CH2

CO2 N CH2: Me+

RX -MeX

CH2 COOH

CH2: Me+

CH2 R

CH2: Me

R-COX -MeX +

CH2 CO R

R-CH=O N CH2: Me
+

OH -H2O CH2 CH R

CH=CH R

Reducerea
+ 3H2 N Pt CH3COOH N H

Tautomeria aminopiridinelor i a hidroxipiridinelor

N
OH

NH2
O

N H

NH

N H

Benzopiridine i derivai

N quinoline

N isoquinoline

N acridine

N phenanthridine

Metode de sintez a chinolinei Sinteza Skraup i sinteza Doebner-Miller

O + NH2

R H+ R

R CO N H

HO R H+ R N H R H+ -H2O

R [O] N H R -H2O

R O NH2 + O R -H2O

R CO N R

HO R H+ N R H+ -H2O

Sinteza Knorr
R O NH2 + RO O H+ -ROH O N H C O R H+ N H O R

Sinteza Konrad-Limpach
O RO NH2 + O R tC
RO

O -ROH

Reacii SE
+ XN+ R RX N HA N+ H + A-

R-COOOH N O N

R-COX

XN+ CO-R

NO2 HNO3 N H2SO4 NO2

Br Br N Br2 CCl4 N Br2 N Br + N

+ N N

SO3H olum N SO3H 90C N olum/H2SO4 170C N

olum N 300C N

SO3H

Reacii SN
NH2 KNH2 N NH3 N + NH2 N

RLi N N R

KOH N N OH N H O

Metode de obinere a izochinolinei Sinteza Bischler-Napieralski

RCOCl NH2 -HCl NH CO R POCl3 -Cl-H+ NH+ C OPOCl2 R
Pd/t -H2 R

-H

NH R OPOCl2

-HOPOCl2 R

Sinteza Pictet-Spengler.
R CH=O NH2 -H2O H+ HC R N R NH R N

Proprieti chimice. Reacii SE

NO2 HNO3 N H2SO4 NO2 N + N

sulfonare

SO3H olum N N

halogenare
Br Br2 N H /AlCl3
+

Reacii de SN
H Nu : N: Nu:N Nu:: N: H Nu : N: H Nu

Compui heterociclici hexaatomici cu dois au mai muli heteroatomi Diazine, triazine i derivai
N N N H pyridazine pipridazine pyrimidine N
N N phtalazine

NH N H piprimidine
N N quinazoline

N N pyrazine
N N quinoxaline

H N N H piprazine
N N phnazine

NH

N N cinnoline

N N N N N N 1,2,3-triazine 1,2,4-triazine 1,3,5-triazine 1,2,4,5-tetrazine

N N

R O N2H4 O -H2O R
R O O R N2H4 -2H2O

R N NH2 O R
R N N R [O] R N N R

R -H2O R N N

O O O N2H4 -H2O

O NH NH O

OH N N OH POCl3 PCl5

Cl N N Cl H2 Pd-C N N

NH + R C NH2

Y CH R1 X

N R N

R1

R = H, alkyle, aryle, OH, SH, NH2, NHR etc. X = Y ou X Y ; X, Y = CH=O, COR, COOR, CN etc.
O NH ROOC N + R C CH2 -ROH NH2 O C N -H2O R R N R R N R OH

R NH O C + CH2 R C NH2 NC
R R NH2 O O + H2N R R

R N R N H
R -2H2O R

R N NH
N N R R

N
R R

NH2
N N R R

[O]

R R

O + O

H2N H2N

R R -2H2O

R R

N N

R R H N

[O]

R R

N N

R R

NH2 + NH2
CH3 N N + CH3-COOR

H N O NH2 OH -H2O

N H CH2 CO CH3

N B -ROH

O NH O NH O
CH=CH2 NH2

HO N OH N HO
HNO2 CH=CH2 N=N+
+

-H+

R O O R N2H4 -2H2O

R N N R

O CO O CO N2H4 -H2O O NH NH PCl5

Cl N H2 N Pd-C Cl
O

N N

COOH NHCO R

NH3 -H2O

CONH2 NHCO R

POCl3 -H2O N

NH R

R O NHCO R NH3

R NH NHCO R -H2O

R N N R

NH2 + NH2 NH2

O O

R R -2H2O

N N

R R

O + O -2H2O

N N

NH2

Oxazine, tiazine i derivai

N N NH N N O O O O O 2H-1,2-oxazine 4H-1,2-oxazine 6H-1,2-oxazine 2H-1,3-oxazine 4H-1,3-oxazine

H N

H N O morpholine
N

N O 1,3-oxazinium
N

O O O 6H-1,3-oxazine 2H-1,4-oxazine 4H-1,4-oxazine

S S S S S 2H-1,2-thiazine 4H-1,2-thiazine 6H-1,2-thiazine 2H-1,3-thiazine 4H-1,3-thiazine

NH

H N

NH

S S S S S 6H-1,3-thiazine 2H-1,4-thiazine 4H-1,4-thiazine 1,3-thiazinium tetrahydro-1,3-thiazine

H N O phnoxazine

H N S phnothiazine

NH3Cl- H2N + OH
H N + S

H N -NH4Cl -H2O
H N S

HO
I2

Compui heterociclici hexaatomici cu oxigen

O pyrylium

O 2H-pyranne
O

O 4H-pyranne

O oxane THP

O O 2-pyrone -pyrone

O 4-pyrone -pyrone
+

O 3,4-dihydro-2H-pyranne

O 5,6-dihidro-2H-pyranne

O ..
+

.. O ..

.. O ..

.. O ..

Comui heterociclici hexaatomici cu oxigen benzocondensai

O O O chromane O -chromne 2H-chromne
O O isopyrilium

O -chromne 4H-chromne

O O coumarine

isocoumarine

O chromone

O chromanone

O pyrylium

O C6H5

C6H5 O flavane

O C6H5 flavanone

O flavone

C6H5

O isoflavone

O OH O flavylium C6H5 O C6H5 flavonol

O OH C6H5 O flavanol OH O C6H5 catchine

OH

O xanthne

O xanthone

O xanthydrol

O xanthylium

Dioxine, ditiine, oxatiine i derivai

O S S O S

O O S O S 1,4-dioxine 1,4-oxathiine 1,4-dithiine 1,4-dioxane 1,4-dithiane

O O dibenzo[1,4]-dioxine

S S thianthrene

S O phenoxathiine

Compui heterociclici heptaatomici (epine)

N N H azpine
N

N N H 1,4-diazpine
N

O oxpine

S thipine
N

N N H 1,2-diazpine

N H 1,3-diazpine

N N H H benzo[b]1,5-diazpine benzo[e]1,4-diazpine

N H dibenzo[e,f]1H-azpine

N H dibenzo[b,e]1,4-diazpine

N O benzo[b]1,4-oxazpine S

N O dibenzo[b,e]1,4-oxazpine

dibenzo[b,e]1,4-thiazpine

Sisteme heterociclice condensate

S N pnam N cfam S N CH3 tropan N quinuclidine

N N

N N H 9H-purine

N N N

NH

N N

N N N indolizine

7H-purine

ptridine

N quinolizinium

N quinolizine

N quinolizidine

N pyrrolizine

N pyrrolizidine

N N NH N porphine HN NH

N HN N NH

N N N corrine

N H -carboline

Purina
1 6

N N
3

5 4

N7 N9 H
8

N N

5 4

NH N

NH2 N N 1 N H N HN H2N

O N N 2 N H

CH3 HN CH2 CH=C CH2OH N N 3 N H N

O HN N 6 N NH HN O

O NH N H 7 N HN O

O NH N H 8 N H O

O H3C O N N N CH3 9 N CH3 HN O

O N N N CH3 10 CH3 H3C O N

O NH N N CH3 11

NH2 N N N H O HN H2N N N H N N HN

NH N N N H OH N H2N N N H N

Pteridina i derivaii si
4 3N 2 d 3 2

N N
8

6 7

N N

N N
O COOH CONH CH (CH2)2 COOH

N
1

O HN H2N N 1 N N HN H2N

N N N

CH2 NH

NH2 HN H2N
O HN O N N N H a O N HN O

N N N

CH2 N CH3 3

COOH CONH CH (CH2)2 COOH

O N N N b H

HN O

CH3

CH3 OH OH OH CH2 CH CH CH CH2 OH 4 N