MAIN SYNTHETICAL METHODS FOR

THE PREPARATION OF HETARENES

1. Ring Synthesis Strategy
1.1. Hydrolytic disconnection
1.2. Redox disconnection
1.3. The mains precursors
1.3.1. Precursors as nucleophiles
1.3.2. Precursors as electrophiles
1.3.3. Precursors as both electrophiles and nucleophiles

2. Substituent modification
3. Nomenclature: I.U.P.A.C., general rules

References:
1. Alan R. Katritzky, A. F. Pozharskii Handbook of Heterocyclic Chemistry 2nd Edition, Pergamon 2000
2. Alan R. Katritzky Short Course in Heterocyclic Chemistry for Ph. D. Students, University of Florida
1996/1997
3. David T. Davis Chimie des Hétérocycles Aromatiques De Boeck Université 1997, Oxford University Press
1992
4. René Milcent Chimie Organique Hétérocyclique EDP Sciences 2003, www.edpsciences.org
5. Jonathan Clayden, Nick Greeves, Stuart Warren, Peter Wothers Organic Chemistry, De Boeck Diffusion
s.a., 2003, Oxford University Press 2001, www.deboeck.com

Modifications (improvements, additions, corrections, up to dates etc.) are subjected to no notice.

Mircea Darabantu, MASTER DIA. I N T R O D-1

MAIN SYNTHETICAL METHODS FOR

THE PREPARATION OF HETARENES

D e f i n i t i o n : the term h e t a r e n e s designes all heterocyclic compounds possessing aromatic

character according to Hückel rule.

Synthesis

Ring Combination of
Substituent
Synthesis the Two
Modification

1. Ring Synthesis Strategy : the following three factors increase the importance
of the ring synthesis
a) Fused Ring vs. Mono cyclic
b) Five vs. Six memebered Ring
c) More Hetero atoms

N
pyridine
N
quinoline
N
acridine
)
Ii it is easier to synthesise a
second ring onto a first one
than to synhtesise a
monocyclic compound.
X X X

))
pyrrole X=NH indole carbazole
thiophene X=S benzothiophene dibenzothiophene
furane X=O benzofurane dibenzofurane
The more heteroatoms one
has in the ring, the more
N methods of synthesis they
N N N
are.
N N N N

)))
pyrimidine quinazoline pteridine

N N N N
Substitution reactions tend
N to be easier on the whole
N N N
H H H when one has fewer
imidazole benzimidazole purine heteroatoms in the ring.
Mircea Darabantu, MASTER DIA. I N T R O D-2

Baldwin’s Rules for 3 to 7 Membered Ring Closure

J. E. Baldwin J. Chem. Soc., Chem. Commun. 1976, 734

- Z: sp3 Exo - Tet Exo-Tet: From 3 to 7 membered rings

X Z X Z
Y Y & FAVOURED
- Z: sp2 Exo - Trig Exo-Trig: From 3 to 7 membered rings
Z
X
Y
X Z
Y-
& FAVOURED
Exo-Dig: From 3 to 4 membered rings
-
X Z
Z: sp Exo - Dig
X Z & DISFAVOURED
Y Y- Exo-Dig: From 5 to 7 membered rings
& FAVOURED
Y: sp3 Endo - Tet
- X Z Endo-Tet: From 5 to 6 membered rings
X Z
Y Y & FAVOURED
Endo-Trig: From 3 to 5 membered rings
Y: sp2 Endo - Trig -
- X Z X Z & DISFAVOURED
Y Y Endo-Trig: From 6 to 7 membered rings
&FAVOURED
Y: sp Endo - Dig
- - Endo-Dig: From 3 to 7 membered rings
X Z X Z
Y Y & FAVOURED

i) all the above rules have empirical support only.

ii) disfavoured does not mean impossible but more difficult to realise.
iii) the basic support of the above rules is stereochemical (bond lenghts and bond angles).
iv) a lot of cases (before and after 1976 are in substantial accord with these rules).

(Y) Endo-Trig
(Z=Y)
CH=O
HO
(Z)
Ring Closure
5 Membered ring
!
OH OH
(Z)
HO Exo-Trig 6 HO O (X) (X)HO N O NH
OH OH Z (X) (Y)
OH (X) Ar Y Ar
CH2OH CH2OH
D-glucose Pyranose chain ring
tautomerism

D. E. Bergmann, Chem. Rev. 1953, 53, 309-353

L. Lázár, F. Fülöp, Eur. J. Org. Chem. 2003, 3025-3042
Mircea Darabantu, MASTER DIA. I N T R O D-2a

Examples : exo-cyclisations according to stereoelectronic requirements in the

transition state
.
2
Br 2
1
. 1
3 3 2
1
.. + Br- .
4
- 6
4
6
3 .
5 5 4 5 five membered
six membered six membered

6-exo-tet cyclisation 6-exo-trig cyclisation 5-exo-dig cyclisation

(Intramolecular SN2) (Intramolecular RA) (Intramolecular RA)
FAVOURED FAVOURED FAVOURED
Stereoelectronically Stereoelectronically Stereoelectronically

3
4
1 2 2
3 Br
H2N N 1O 5
O
H H O OH
O
aziridine five membered
(three membered)
(tetrahydrofuran-2-one)

3-exo-tet cyclisation 5-exo-trig cyclisation

(Intramolecular SN2) (Intramolecular SN2)
FAVOURED FAVOURED
Stereoelectronically Stereoelectronically

G e n e r a l i s a t i o n:

( )k ( )k
lone Y ..
lone Y .. σ∗
X X
pair
pair empty (donor) π∗
(donor) (acceptor) empty
(acceptor)
n-exo-tet cyclisation n-exo-trig cyclisation
k=0-4 k=0–4
FAVOURED FAVOURED
Stereoelectronically Stereoelectronically

exo-dig cyclisations are favoured for five to

seven membered rings
Mircea Darabantu, MASTER DIA. I N T R O D-2b

Examples: endo-cyclisations according to stereoelectronic requirements in the

transition state
NOTE: only 6- and 7-endo-tet cyclisation are favoured
all 3 – 7-endo-dig cyclisations are favoured
almost all 3 – 7-endo-tet cyclisations are less favoured
Plausible but…

+ + +
O lone
O O OEt pair
3 H H H (donor)
N ..
π∗ empty
4
2 OEt OEt O
N .. (acceptor) OEt
1NH
.. 2
5
HN H lone
5-endo-trig cyclisation pair π∗ empty
DISFAVOURED (donor) (acceptor)
(Intramolecular 1,4-addition) Inappropriate Too far...
orientation
This is the real:
3
4
2 5-exo-trig cyclisation
1NH 5 FAVOURED
2 HN
.. O O
EtO

A 6-endo-trig cyclisation: favoured, occuring in 89 % yield

O - MeO2C MeO2C O
MeO2C O O
∗ 1
MeOOC π
Base ..
2 6

O 3 O
O 5 H
4
O
Appropriate
orientation
trans stereochemistry
with respect to
cyclanone ring

A 5-endo-dig cyclisation: favoured

π∗ empty (acceptor)
inapropriate orientation
i) 5-endo-dig cyclisation
O O FAVOURED O
+ O
Base ii) H
2 4
3 5
_
1O - O ..
OH Ar Ar O
lone π∗ empty (acceptor)
pair apropriate orientation
(donor)
Mircea Darabantu, MASTER DIA. I N T R O D-3

1.1. Hydrolytic disconnection

- hydrolytic disconnections of the double bonds are very useful since most of the ring closures to afford
heterocyclic systems are simple condensation

H+ / -H2O
i) Nucleophilic addition
R1 ii) Elimination R1
O + H2N-R3 N R3 + H2O c o n d e n s a t io n
R2 R2
Imine
Schiff base

Example 1:

originates
from...
R1 R1
N R3 O + H2N-R3 good o p t i o n !!
R2 R2 precursors
Target
Compound R1
NH + HO-R3 bad o p t i o n !!
R2 precursors
R1
OR3
e.g.
R2 NH2
Example 2:

hydrolytic disconnection

EWG EWG
O + H2C precursors
(EWG) (EWG)

EWG: Electro(no) Withdrawing Group

CO, COOR, CN, etc.

Example 3:

R R precursor: good option !!

N O NH2
heterocyclic compound
seen as a cyclic imine

- NH3
R R R ? bad option
N NH OH H2N O
heterocyclic compound
seen as a cyclic amine
Mircea Darabantu, MASTER DIA. I N T R O D-4
Example 4:
Imine or enamine ? It doesn’t matter…
H H
sp2
sp3
R N R OH NH2
H H
(masked)
H
enamine
R O NH2
H H
sp2
sp3 H
R N R N
H
(masked) imine
enamine
Example 5:
Retrosynthesis of pyrroles seen as hydrolytic disconnection:

basic basic
center +H+ +H+ center
4 3

H3C 5 2 CH3 H3C CH3 H3C CH3 H3C CH3

N1 O O
H O NH H O N
H H NH3
2,5-dimethylpyrrole
seen as acid
acid -H+ center
double enamine center -H+
enol enamine

Example 6: the importance of the formal charges

Rings containing Nitrogen

+1
+1 +1 H
H H -1 H
-2
+1 -3 +1 +1 +2 +1
+1 R
R N OH NH2 R O NH2 2 x (+1)
H -2 +1 -3 2 x (+1) -2 -3
+1

Rings containing Sulphur

+1 the best precursor
+1 +1 H
H H -1 H
-2
H
+1 -2 +1 +1 +2 +1
H
+1 R +1 +1
R
&
R S OH SH O SH
-2 +1 -2 -2 -2

R
%
Rings containing Oxygen
+1 +1 H
+1
best X
Y
H H -1 H
-2 electrophile best
+1 -2 +1 +1 +2 +1 nucleophile
+1 R +1 +1
R O OH OH R O OH
-2 +1 -2 -2 -2
Mircea Darabantu, MASTER DIA. I N T R O D-5

To be kept in mind:
1. If a hydrolytic disconnection appears suitable, the best pair nucleophile-electrophile sould be
considered
2. All cyclisations (or cyclocondensations) involve classic tautomerism: keto-enolic, imino-enamine, etc.
3. During cyclocondensation (or retrosynthetic hydrolytic disconnection) no global redox process,
involving the whole molecule occurs.

1.2. Redox disconnection

-this methodology provides information about the general strategy to be used to access the target
compound: is there any redox step ?
Example 1:
- a five membered hetarene:
it looks like
"organic"
O O
i) cut (remove) the bonds add two functional
between the organic groups at both ends
and inorganic parts of the "cation"
ii) add the formal charges +1 +1 to "neutralise" charges -1
N -1
H HO ] [OH
+1 +1
N -1-3 3x(+1)
H -3
NH3
it looks like precursors
it sounds like
"inorganic" ammonia
Obs: the structure of the target compound (bond connection and aromaticity) is automatically issued by
preserving the formal charges of each of the involved (hetero)atoms: no redox step in the synthesis
Example 2:
- a six membered hetarene
redox
disconnection
+2 +1
H3C N CH3 H3C +2 +1 CH3 H3C -2 CH3
N3- -2 O OH
+1
-3 NH
3 3x(+1)

h
???
1 3 5 7
H3C CH3
2[H] 2 6
4
O O
H3C CH3
O O
2,6-heptanedione

☺
Z-1,4-diketone
currently nonavailable commercial product
difficult to obtain
is the above disconnection useful for a chemist ? Why ?
a) Because it provides rapidly the type of precursors
b) Because it provides rapidly the most convenient precursors.
c) Because it infers that if, for reason of availability, a redox step is revealed (e.g. reduction) by the
redox disconnection, in the synthesis of the target molecule a redox step must be accomplished: e.g.
oxidation.
Mircea Darabantu, MASTER DIA. I N T R O D-6
The direct synthesis:
+ NH3
-H2O

H3C CH3 H3C CH3 H3C CH3

OO O O
NH NH2

-H:- anticipated oxidation step

H H 4
-H2O + [O] 5 3

H3C N CH3 H3C N CH3 -H2O H3C 6 N 2 CH3

OH H 1
H 2,6-dimethylpyridine
-H+

1.3. The main precursors

1.3.1. Precursors as Nucleophiles: this is the traditional route to bring heteroatoms (N, S, O) in the target
compound
Example 1: b r i n g i n g one heteroatom in the target compound:

NH3 H2S H2 O

4
+ 3 4
+ 3 4
+ 3
5 2 5 2 5 2
N1 S O
H 1 1

Example 2: b r i n g i n g two heteroatoms in the target compound:

H2N-NH2 HO-NH2
hydrazine hydroxylamine

4
+ 3
4
+ 3
5 N2 5 N2
N1 O1
H
pyrazole isoxazole

Example 3: b r i n g i n g three atoms in the target compound:

thiourea thioamides urea amidines guanidine
NH2 NH2 NH2 NH2 NH2

S NH2 S R O NH2 HN R HN NH2

+
4
+
+ +
6 4
+ 4
+
4
5
N3
5
N3 HN 1 5 5 N3 5 N3
6 2 6 2
S 2 NH2 S 2 R 4
1 1 O 2 N3 N1 R N1 NH2
2-substituted thiazoles 2-pyrimidone 2-substituted pyrimidines
Mircea Darabantu, MASTER DIA. I N T R O D-7

Example 4: b r i n g i n g three, four and five atoms in the target compound: benzoderivatives
NH2

NH2
NH2 NH2

+ 4 8
+ +
5 1 5 4
N
6 3 7 2 6 3

7 2 6 3 7 N2
N 5
N
8 1 4 8 1
Quinoline Quinoxaline Isoquinoline

1.3.2. Precursors as Electrophiles:

Example 1: b r i n g i n g one atom:
δ- 4
O NH2 O 3a N3

)
δ+ 5
R R
R LG 6
2
NH2 Cl 7aN1
7 H
LG: leaving group as LG:- 2-substituted
e.g. Cl as Cl-; R'O as R'OH etc. benzimidazoles

Example 2: b r i n g i n g two atoms:

δ- δ- R1 O R1
O O :NH2
)
4
δ+ δ+ N3
δ+ R δ+ 5
OR Cl :S R2
δ- δ - 1S R2 2
LG LG
2,4-disubstituted
thiazoles
Example 3: b r i n g i n g three atoms:
δ-
Oδ
- O O 4
O R 3 R

)
δ+ δ+ R
5
R R R 1X N2

1,3-dicarbonylic HX NH2 3,5-disubstituted

compounds X = NH pyrazoles
X = O isoxazoles

O
δ- O
Oδ
-
O

)
5 4 N3
δ+ δ+ OR NH2
RO OR
O 6 N 1 2 R'
O OR HN R' H
malonic esters
2-substituted-pyrimidin-
-4,6-dione
Mircea Darabantu, MASTER DIA. I N T R O D-8

O
δ- R
R
O 5 4
δ+ 3

)
6
R
2
NH2 7 N
δ+ 8 1
acrylic derivatives 4-substituted-
-quinoline
Example 4: b r i n g i n g four atoms:
4 3

)
δ+ δ+ δ+ δ+
R R R R R R
5 X 2
O O O O
1
δ- δ-
H2X (X = NH, S)
1,4-diketones

Note: electrophilic fragments usually do not bring heteroatoms in the target compound

1.3.3. Precursors as both Electrophiles and Nucleophiles:

Example 1: b r i n g i n g two atoms:

δ- as Nu:-
R2 R2 4
NH2 N3

)
O LG
δ+ R3 O R3 5 O 2 R
1
R LG R1
as E+ O 1
2,4,5-trisubstituted-
LG: leaving group as LG:-
-oxazoles
e.g. Cl as Cl-

O H O
as Nu:- O 5 4
δ- 3 OR
O OR

)
LG 6
LG
δ+ δ+ 2
OH HO OR 7
O LG O O
δ- as E+ HO LG 8 1
3-substituted-
LG: OR, Halo -coumarines

Example 2: b r i n g i n g three atoms, see Example 1

as E+
δ-
R3 O
δ+
R2 NH2 as Nu:-
an α-aminoketone
Mircea Darabantu, MASTER DIA. I N T R O D-8a

Example 3: acid chlorides as good electrophiles to generate good nucleophiles.

The target compound:

O
5
R1 4
O1 R1 =/ R2 =/ H
3N 2
R2

Retrosynthetic analysis:
O O O
5
R1 4 hydrolytic disconnection R1 R1
O1 N-3-C-2 and C-2-O-1 O OH OH
3N 2
N NH2 O
R2 R2 R2
poor ability as Leaving Group
weak nucleophile in this environmen
O O
O
R1 O R1 OH
OH R1
O
NH2 Cl R2 HN O
C HN OH
R2 R2
better LG than HO weak
C=O more electrophilic electrophile

Solution of the problem:

good LG
R2 O
O O O O _
R2 O
R1 OH R1 O
Cl R2 O R1
O
HN O Δ excess N O Nucleophile -H+
C C N
H
R2 R2
R2

Note: obsolete cyclisation of α-aminoacids as double protected N-, COO- form (oxazoline)
Mircea Darabantu, MASTER DIA. I N T R O D-9
2. Substituent modification
- the below three main types of substituent modification are of general interest

i) nucleophilic displacement:

π + Nu:- π + LG:-
X LG X Nu

ii) electrophilic displacement:

H E
π + E+ π + H+
X X

iii) electrophilic displacement via metallation:

π + R-Mn
- RH
π + E+
- Mn+
π Mn: LiI, MgII etc
X H X Mn X E

3. Nomenclature: IUPAC general rules

- important trivial names are given at the beginning of each chapter: e.g. pyridine instead of azabenzene
- the type of heteroatom present in the ring is indicated by the below prefixes, in decreasing order of
citation (nomenclature as a):

O oxa > S thia > Se selena > N aza > P phospha > As arsa > Si sila > B bora etc.

Note: the final a is however elided before a vowel e.g. azaole → azole

- two or more identical heteroatoms are indicated by dioxa, triaza, etc.

- If different, the prefixes should be combined according to the above order: e.g. thia-aza-ole → thiazole;
e.g. oxa-diaza-ole → oxadiazole; e.g. oxa-thia-ane → oxathiane.
- numbering of the positions starts at an oxygen, sulphur or nitrogen (in decreasing order of preference)
and continues in such way that the heteroatoms are assigned the lowest possible numbers.
- other things being equal, numbering starts at a substituted rather than at a multiply bonded nitrogen
atom.
3 5
4
N N1
5 2 4 2
N1 N3
CH3 CH3
1-methyl-1,3-diazole 3-methyl-1,3-diazole
1-methylimidazole 3-methylimidazole

MAXIMUM UNSATURATION is defined as THE MAXIMUM POSSIBLE NON CUMULATIVE

DOUBLE BONDS BY CONSIDERING:
O- two valencies
S – two valencies
N – three valencies
Mircea Darabantu, MASTER DIA. I N T R O D-10

The Hantzsch-Widman Nomenclature for Heterocyclic Compounds

Rings w i t h Nitrogen
Ring Maximum Unsaturation One Double Bond Saturated
Size
3 Eng. 3 2 3 2 - - Eng. 3 2 3 O1
-irine N N1 -iridine N1 N2
Rom. 1 H Rom. H H
-irină 1-azirine 2-azirine -iridină aziridine oxaziridine
4 Eng. 3 2 Eng. 3 2 3 2 Eng. 3 2 3 O2
-ete 4 N
-etine 4 N1 NH -etidine
1 4 4 NH 4 NH
1 1 1
Rom. azete Rom. 1-azetine 2-azetine Rom. azetidine 1,2-oxazetidine
-etă -etină 2 2 -etidină
3 NH 3 N
4 O1 4 O1
2H-1,2-oxazetine
4H-1,2-oxazetine
5 Eng. 3
Eng. 4 N3 4 N3 4 N3 Eng. 4 NH
-ole 5
-oline 5
-olidine
5 2 2 2 5 2
N1 O1 S1 O1
Rom. H Rom. 2
Rom.
-ol 1,3- 1,3- -olină Δ -thiazoline -olidină 1,3-oxazolidine
diazole oxazole
imidazole
6 Eng. 4 - 4 Nomenclature is made by using the
-ine 5 N3 5 N3 prefix perhydro (total hydrogenated)
6 2 6 2 which precedes the name of the
Rom. N N corresponding non saturated structure
1 1 4
-ină 3
1,3-diazine 4,5- 5 NH
pyrimidine dihydropyrimidine
6 1 2
7 Eng. 5
N4 - - N
-epine 6 3 H
perhydro-1,3-diazine
7 2
Rom. O1
-epină
1,4-oxazepine
8 Eng. 5 - -
4 6
-ocine
3 7
Rom.
2 N 8
-ocină
1
azocine
9 Eng. 6 5 - -
-onine 7 4
8 3
Rom. 1
onină 9 N 2
H
1H-azonine
Mircea Darabantu, MASTER DIA. I N T R O D-11

The Hantzsch-Widman Nomenclature for Heterocyclic Compounds

Rings w i t h o u t Nitrogen
Ring Maximum Unsaturation One Double Bond Saturated
Size
3 Eng. 3 2 3 2 - - Eng. 3 2 3 2
-irene O S -irane O S
1 1 1 1
Rom. oxirene thiirene Rom. oxirane
irenă -iran thiirane
4 Eng. Eng. - Eng. 3 4 3 4
3 4 3 S2
-ete -etene -etane 2 O1 2 S O1
Rom. 2 O1 4 O1 Rom. Rom.
-etă oxete 1,2-oxathiete -etenă -etan oxetane
1,2-oxathietane
5 Eng. 4 3 4 3 Eng. 4 3 4 3 Eng. 5 4 4 3
-ole 5 2 5 2 -olene 5 2 5 2 -olane 1O O3 5 2
O1 S1 O1 S1 2 S1
Rom. Rom. 2 3 Rom.
oxole thiole Δ -oxolene Δ -thiolene 1,3-dioxolane
-ol furane thiophene -olen -olan thiolane
6 Eng. 4 - Eng. 5
-in 5 3 -ane 6 4

6 2 1O O3
Rom. S1 Rom. 2
-ină H -an 1,3-dioxane
thiin
7 Eng. 5 4 5 4 - Eng. 5 4
-epin 6 3 6 O3 -epane 6 O
3

Rom. 7 2 7 2 Rom. 7 2
O O S1
epină 1 1 -epan
oxepin 1,3-dioxepin thiepane-3-one
8 Eng. - Eng. 5 4
-ocin 4 -ocane 6 3
5 5 4
6 3 6 3 7 2
Rom. Rom.
8
S1
ocină 7 2 7 2 -ocan
O 8
S1 thiocane
8 1
4H-oxocin 2H-thiocin
9 Eng. 6 5 - Eng. 6 5
-onin 7 4 -onane 7 4
8 3 8 3
Rom. Rom.
onină 9 O 2 -onan 9 O 2
1 1
oxonin oxonane
Mircea Darabantu, MASTER DIA. I N T R O D-12

- indicated hydrogen: H in compounds possessing maximum unsaturation, if the double bonds can be
arranged in more than one way, their positions are defined by indicating the nitrogen or carbon
atoms which are not multiply bonded and consequently carry an “extra” hydrogen atom: 1H, 2H,
etc.
- in partially saturated compounds, the position of the hydrogen atoms can be indicated by the
prefixes dihydro if convenient suffix is not available
- in partially saturated compounds, the position of the double bond can be indicated by the symbol Δa,b
which indicates that the double bond is between the atoms numbered “a” and “b”

Example 1:
4 3 4 3 4 3
5 2 5 2 5 2
N1 N1 N1
H
1H-pyrrole 3H-pyrrole 2H-pyrrole

Example 2:
4 4 4 4 4 4
5 3 5 3 5 3 5 3 5 3 5 3
6 2 6 2 6 2 6 2 6 2 6 2
S S1 S1 S1 S1 S1
1
H
thiane (I.U.P.A.C.) 1H-thiin 2H-thiin 4H-thiin 3,4-dihydro-2H-thiin 5,6-dihydro-2H-thiin
2,3-dihydro-4H-thiin
3,4,5,6-tetrahydro-2H-thiin

with suffix according to IUPAC: in no suffix available according to IUPAC

Note: the number of the indicated hydrogen is the lowest possible

Example 3:
4
5S 3
2H,6H-1,2,5-dithiazine → max. unsaturation possible is 1 double bond: suffix i n e
6 NH → order of citation: S, S > N
S 2
1 → supplementary hydrogen at N-2 and C-6: 2H,6H
4
5S 3 4H,6H-1,2,5-dithiazine → max. unsaturation possible is 1 double bond: suffix i n e
→ order of citation: S, S > N
6 N
S 2 → supplementary hydrogen at C-4 and C-6: 4H,6H
1

Example 4:

4
5
N 3 6H-1,2,5-thiadiazine → max. unsaturation possible is 2 double bonds: suffix i n e
6 N → order of citation: S > N, N
S 2 → supplementary hydrogen at C-6: 6H
1
4
5 3 4H-1,2,5-thiadiazine → max. unsaturation possible is 2 double bonds: suffix i n e
N
→ order of citation: S > N, N
6 N → supplementary hydrogen at C-4: 4H
S 2
1