OrganoSulfur Compounds

Sulfur (S)

 S and O :: atomically similar

 Sulfur also intimately involved in biological processes
 Sulfur forms two bonds in a manner similar to O
 But sulfur may form more because of the presence of d-orbitals, e.g.,
–S(O)– and –S(O2)–

MEDC 527 Fall 2008 1

 OrganoSulfur Compounds

Sulfur compounds that have an O analog … without O analog

H S H Hydrogen sulfide H O H water R'
RS S
ul
fox
i
des
(O
S=
+4
)
O
R S H Thioalcohol (mercaptans) R O H
R'
R S R' Thioethers (sulfides) R O R' RSOS
ul
fon
es
(O
S=
+6
)
O

R S S R'Disulfides R O O R'
OH
RS Su
l
fi
nicA
ci
ds(
OS=
+4
)
OH O O
R Thioacids R
O
H
S OH
RSOS
ul
fon
i
c A
c
id
s(
OS=
+6
)
O
SH O
R Dithioacids R O
H
S OH
R
OSOSu
l
fat
es(
OS=
+6
)
O
R R
R S Sulfonium ion R O + Oxonium ion
R R

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 OrganoSulfur Compounds

Nomenclature

Thiols: CH3SH methane thiol or methylmercaptan or mercaptomethane

PhSH benzene thiol or phenylmercaptan or mercapto benzene

Sulfoxides and Sulfones CH3S(O)CH2CH3 methyl ethyl sulfoxide

CH3S(O2)CH2CH3 methyl ethyl sulfone

S
Indene 1-thiaindene

S
Cyclohexane Thiocyclohexane

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 OrganoSulfur Compounds

• Common and Important Sulfur Compounds

+
H3NCH(COO-)CH2CH2CONHCH(CH2SH)CONHCH2COO-
— Glutathione or
+
H3NCH(COO-)CH2CH2CO-CYS-GLY
 Involved in a variety of detoxification, transport and metabolic
processes
 Substrate for peroxidase reactions
 Maintains balance of sulfhydryl groups (-SH of Cys) in proteins
NH 2

N N
O O H C
3 CH 3
O O
— Coenzyme A HS
N N N N
O P P O
H H OH O O O
H H
H
OH OH
Coenzyme A (CoASH)

 Plays a major role in the biosynthesis and metabolism of a

number of important molecules, including fatty acids

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 OrganoSulfur Compounds

• Common and Important Sulfur Compounds

NH2

N N
— S-Adenosylmethionine NH2 CH3
N N
 Plays a major role in the methyl S
HOOC +
transfer reactions, e.g. onto O
H H
phenolic groups or DNA … H
SAM OH OH

— Heparin, Heparan Sulfate, Chondroitin Sulfate …

 Glycosaminoglycans have numerous physiological roles

_ _ _ _
CH2OSO3 COO CH2OH CH2OSO3 CH2OSO3
O O O O_ O O_ O
OH OH OH COO OH COO OH
OH OH
O O O O O O O
_ _ _ _
NHCOCH3 OH NHSO3 OSO3 NHSO3 OH NHSO3

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 Heterocycles Containing Sulfur

 Basic Ring Systems

S S N
S
T e tr a h y d r o th io p h e n e T h io p h e n e 1 ,3 - th ia z o le
( th io la n e ) ( T h io le )

 Examples in Drugs O
S COOH
OMe N
HN H2N
N
N N O S
CH 3 NH2
N N S S
CH 3 O O
S
methapyrilene H2N
ceftizoxime thiazolsulfone
(Antihistamine) (Antibiotic) (Antimalarial)

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 OrganoPhosphorus Compounds

Phosphorus (P)

 N and P :: atomically similar

 Phosphorus is an important part of most important biological
materials, DNA, RNA, ATP, …
 Phosphorus forms three bonds like N
 But P may form more because of d-orbitals

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 OrganoPhosphorus Compounds
Comparison of reactions of P and N

• Similarities
….in acidification …. in quaternary salt formation ….in oxidation

H3C - O
.. + C l- .. +I ..
R P R
HCl R P R CH3I R P R H 2O 2
R P R R P R R P R
R R R
R R R
- O
..
+ NC l R - ..
R N R
HCl .. H3C + I H 2O 2
R
R N R CH3I
R N R R N R R N R
R R
R R R R

• Differences
• Maximum # bonds with N = 4; it is 5 or 6 with P depending on the number of d-
orbitals involved
• P does not form many unsaturated compounds because of poor p-p overlap, e.g, no –
P=P- known (diazo are known); nor are phosphorus analogs of nitriles or amides
• Few unsaturated P compounds known, nearly all have P=O (double bond with
oxygen)
• P does not give stable aromatic compounds, e.g., no phosphorus analog of pyrrole or
pyridine is known

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 OrganoPhosphorus Compounds

Phosphate buffer

O O pKA=7.20 O O
pKA=2.15
- - pKA=12.38 -
HO P OH HO P O HO P O O P O-
OH OH O- O-

N N
Adenine
N N
5’
OCH2
O
N
N 4’ H H 1’
O O O H O
H2 N N 3’ OH2’
-O P O P O P O C HN
Uracil
O
O- O- O- H H
O
H2 O N
H -O P O C
5’ O
ATP OH OH O H H 1’
H
RNA 3’ OH
O

MEDC 527 Fall 2008 9