Special Topic
Sulfur
Going beyond the bad smell…
Gaëlle Mingat
10/10/12
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Sulfur, going beyond the bad smell…
Overview
I.
General properties
II.
Some name reactions involving sulfur
III. Sulfur ylides and the Corey-Chaykovsky reaction
IV. Chiral sulfur
V. Sulfur migration in organic synthesis
VI. Sulfur in the food industry
VII. A « bad smell » example, just one…
VIII. Sulfur in perfumes
10/10/12
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I. General properties
- abundant, multivalent non-metal
- cyclic octatomic molecule: S8
- Found in nature as the pure
element, sulfide (S2-) and sulfate
(SO42-) minerals
- Either an oxidant or a reducing agent
Bright yellow solid
Melting point: 115.21 °C, blood-red liquid
Burns with a blue flame better observed in the3 dark
I. General properties
- Once extracted from salt domes: Frasch process
→ 99.5% pure melted product
- Today produced as a by-product by removing organosulfur
compounds from natural gas and petroleum
Carrying sulfur blocks from a
volcano, Indonesia
Hydrodesulfurization
R-S-R + 2H2 → 2 R-H + H2S
Conversion of hydrogen sulfide in elemental sulfur via the
Claus process
3 O2 + 2 H2S → 2 SO2 + 2 H2O
SO2 + 2 H2S → 3 S + 2 H2O
Stockpiles of elemental sulfur
recovered from hydrocarbons,
Alberta, Canada
World production in 2011: 69 M tones
→ China (9.6), US (8.8), Canada (7.1), Russia (7.1)
Dibenzothiophene, a composant of crude
oil
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I. General properties
Electronic configurations:
6C 1s2 2s2 2p2
8O 1s2 2s2 2p4
16S 1s2 2s2 2p6 3s2 3p4
O: r = 70.2 pm
S: r = 104.9 pm
C-O: 355-380 kJ/mol
C-S: 255 kJ/mol
C=O: 678 kJ/mol
C=S: 377 kJ/mol
Longer and weaker  bond
Weaker π bond (bad overlap)
Schaumann E.; Top Curr. Chem. 2007, 274:1-34 (DOI 10.1007/128_2006_105)
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I. General properties
Electronegativities
→ electron affinities, ionization potentials, bond energies
Sanderson: «compactness » of an atom’s electron cloud
→ Polarizability of S
 C-S bond: polarization not pronounced
 Ionic character lessened as compared to oxygen counterparts
(hydrogen bonding less important)
 Aromaticity:
furan (Eres = 75kJ/mol) < thiophene < benzene (Eres = 113 kJ/mol)
Schaumann E.; Top Curr. Chem. 2007, 274:1-34 (DOI 10.1007/128_2006_105)
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I. General properties
Cysteine
Essential element for life
Methionine
Glutathione : antioxydant
(Cysteine/Glycine/Glutamate)
Disulfide bonds : mechanical strength, insolubility of keratin
(hair, outer skin, feathers) and pungent odor when burned
Thioester acetyl coenzyme A
Cystine
(dehydrogenated cysteine)
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I. General properties
Biotin (vitamin H)
Essential element for life
Penicillin core structure
Thiamine (vitamin B1)
Umpolung chemistry in nature
« S-adenosylmethionine »: Nature’s
iodomethane or diazomethane equivalent
Sulfanilamide (sulfa drug)
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I. General properties
Thiols: R-SH
Important chemical functionalities
Sulfides: R-S-R
Sulfoxides
Sulfones
Sulfonic acids
Sulfimides
Sulfoximides
Sulfonediimides
Sulfonamides
(sulfa drugs)
Sulfinic acids
Sulfinamides
Sulfenic acids
Sulfenamides
Thiocarbonyls: thioamides
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I. General properties
S-nitrosothiols
Important chemical functionalities
Thiocyanates
Isothiocyanates
Sulfines
[R3S]+
Sulfonium, oxosulfonium ion
Sulfonium, oxosulfonium ylide
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II. Some name reactions involving sulfur
- Lawesson’s reagent: from a ketone to a thioketone
→ Enones, esters, lactones, amides, lactams, quinones
- Sulfur as a reducing agent
→ NaHSO3, Na2SO3, Na2S2O3, Na2S·9H2O, SOCl2, SO2...
→ Me2S in ozonolysis to prevent further oxidation of products (still used??)
- Oxidation reactions
→ Pfitzner-Moffatt
▫ urea byproducts difficult to remove
→ Swern
▫ better yields, fewer side products than P-M
→ Corey-Kim
▫ T > -25°C allowed but Me2S (toxic + bad smell)
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Kürti L., Czako B.; Strategic Applications of Named Reactions in Organic Synthesis (2005)
II. Some name reactions involving sulfur
- Oxidation reactions
→ Davis’ oxaziridine oxidations
▫ 2-arylsulfonyl-3-aryloxaziridines
▫ sulfides and selenides to sulfoxides and selenoxides
▫ alkenes to epoxides
▫ amines to hydroxylamines and amine oxides
▫ organometallic compounds to alcohols and phenols
▫ most widespread application: oxidation of enolates to α-hydroxy
carbonyl compounds (acyloins)
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Kürti L., Czako B.; Strategic Applications of Named Reactions in Organic Synthesis (2005)
II. Some name reactions involving sulfur
- Olefinations
→ Bamford Stevens
▫ aprotic solvents: Z-alkenes major / protic solvents: mixture of E- and Z-alkenes
→ Shapiro
→ Corey-Winter
→ Julia-Lythgoe
▫ E-alkenes major
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Kürti L., Czako B.; Strategic Applications of Named Reactions in Organic Synthesis (2005)
II. Some name reactions involving sulfur
- Rearrangements
→ Mislow-Evans
→ Pummerer
→ Ramberg-Bäcklund
→ Stevens
▫ 1,2-rearrangement of a sulfonium salt giving a sulfide, using a strong base
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Kürti L., Czako B.; Strategic Applications of Named Reactions in Organic Synthesis (2005)
II. Some name reactions involving sulfur
→ Barton-McCombie radical deoxygenation reaction
▫ radical substitution via a thiocarbonyl
→ Burgess dehydration reaction
→ Chugaev elimination reaction
▫ alkenes from alcohols via a xanthate undergoing a syn-elimination
→ Corey-Nicolaou macrolactonization
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Kürti L., Czako B.; Strategic Applications of Named Reactions in Organic Synthesis (2005)
III. Sulfur ylides and the Corey-Chaykovsky reaction
Schaumann E.; Top Curr. Chem. 2007, 274:1-34 (DOI 10.1007/128_2006_105)
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III. Sulfur ylides and the Corey-Chaykovsky reaction
Corey-Chaykovsky reaction:
JACS 1965, 87 (6), 1353
Schaumann E.; Top Curr. Chem. 2007, 274:1-34 (DOI 10.1007/128_2006_105)
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III. Sulfur ylides and the Corey-Chaykovsky reaction
Enantio- and diastereocontrol in sulfur ylides-mediated epoxidations: Aggarwal’s work
Schaumann E.; Top Curr. Chem. 2007, 274:1-34 (DOI 10.1007/128_2006_105)
Aggarwal V.; Chem. Commun. 2003, 2644
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III. Sulfur ylides and the Corey-Chaykovsky reaction
Examples of sulfur ylides mediated asymmetric epoxidations
Schaumann E.; Top Curr. Chem. 2007, 274:1-34 (DOI 10.1007/128_2006_105)
Aggarwal V.; Chem. Commun. 2003, 2644
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III. Sulfur ylides and the Corey-Chaykovsky reaction
The example of stabilized ylides (additional anion-stabilizing group): trans-diastereoselectivity
Cross-over experiments:
 Either anti- or syn-sulfonium salt furnishes only the trans-epoxide containing the
more reactive aldehyde (p-NO2C6H4)
→ both syn- and anti-betaine are formed reversibly
 Trans-selectivity because barrier to torsional rotation in anti-betaine smaller
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Aggarwal V.; Chem. Commun. 2003, 2644
III. Sulfur ylides and the Corey-Chaykovsky reaction
Semi-stabilized ylides: trans-diastereoselectivity
Cross-over experiments:
 Anti-betaine reacted with a more reactive aldehyde: no incorporation of this aldehyde in the
final epoxide
 With syn-betaine: complete incorporation of the more reactive aldehyde
→ Anti-betaine irreversibly formed
→ Syn-betaine reversibly formed
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Aggarwal V.; Chem. Commun. 2003, 2644
III. Sulfur ylides and the Corey-Chaykovsky reaction
Control of enantioselectivity
1)
2)
3)
4)
Formation of a single diastereoisomeric sulfonium ylide
High level of control of ylide conformation
High level of control in face selectivity of the ylide
Non-reversibility of the anti-betaine formation
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Aggarwal V.; Chem. Commun. 2003, 2644
III. Sulfur ylides and the Corey-Chaykovsky reaction
Control of enantioselectivity: effect of protic solvents
Aggarwal
If low enantioselectivity:
Protic solvents or addition of Li cations makes the reaction less reversible
(if reversibility of betaine formation is the cause)
If low diastereoselectivity:
Aprotic solvents and avoidance of species capable of solvating alkoxides
(increase of rotation barrier so reaction more reversible – displacement equilibrium to left)
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Aggarwal V.; Chem. Commun. 2003, 2644
IV. Chiral sulfur
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Schaumann E.; Top Curr. Chem. 2007, 274:1-34 (DOI 10.1007/128_2006_105)
IV. Chiral sulfur
25
Schaumann E.; Top Curr. Chem. 2007, 274:1-34 (DOI 10.1007/128_2006_105)
IV. Chiral sulfur
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Schaumann E.; Top Curr. Chem. 2007, 274:1-34 (DOI 10.1007/128_2006_105)
IV. Chiral sulfur
http://www.chemtube3d.com/Oppolzer.html
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Schaumann E.; Top Curr. Chem. 2007, 274:1-34 (DOI 10.1007/128_2006_105)
IV. Chiral sulfur
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Schaumann E.; Top Curr. Chem. 2007, 274:1-34 (DOI 10.1007/128_2006_105)
V. Sulfur migration in organic synthesis
Stuart Warren’s work; preliminary observation
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Warren S.; Phosphorous, Sulfur and Silicon 1999, 153-154, 59
V. Sulfur migration in organic synthesis
D. House, S. Warren: stereospecificity in the migration of « SPh »
Secondary OH = LG
Primary OH = Nu
Secondary OH = LG
Primary OH no more a Nu
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Warren S.; Phosphorous, Sulfur and Silicon 1999, 153-154, 59
V. Sulfur migration in organic synthesis
Competition between 2 hydroxyl groups
Is it possible to control which OH leaves, which acts as a Nu and where it attacks??
Primary OH = LG
SPh = Nu
Primary OH = LG
Secondary OH = Nu
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Warren S.; Phosphorous, Sulfur and Silicon 1999, 153-154, 59
V. Sulfur migration in organic synthesis
Kinetic resolution of racemic and enolisable 2-PhS aldehydes
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Warren S.; Phosphorous, Sulfur and Silicon 1999, 153-154, 59
VI. Sulfur in the food industry
 About 10% of the volatile components detected in foods and beverages contain sulfur
 Volatile organic sulfur compounds: extremely low odour threshold
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→ highly important for flavours and aromas
Goeke A.; Sulfur reports 2002, 23, 3, 243
VI. Sulfur in the food industry
The Maillard reactions (1911)
▫ chemical reactions occuring while cooking food
▫ amino acids + sugars form a brownish mixture when heated to high temperature
▫ responsible for many colors and flavors in foods:
- the browning of various meats like steak
- toasted bread, burnished crust of brioche, cakes, yeast, biscuits
- French fries, fried onions
- malted barley (whiskey, beer)
- dried or condensed milk (dulce de leche)
- maple syrup
- roasted coffee
▫ importance for the food industry in order to control the aspect, the taste and the
conservation of food (incorrect preparation or storage produce off-flavours)
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VI. Sulfur in the food industry
Role of cysteine and cysteine-S conjugates as odour precursors
Maillard reaction: cysteine + sugars (meat flavour…)
Roast meat
Popcorn
Basmati rice
 Cheddar cheese: methanethiol, hydrogen sulfide, dimethyl disulfide, dimethyl trisulfide
→ products of the catabolism of methionine and cysteine by bacteria
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Starkenmann C.; Flavour Fragr. J. 2008, 23, 369
VI. Sulfur in the food industry
Role of cysteine and cysteine-S conjugates as odour precursors
 Wine and passion fruit
Wine treated with copper sulfate → « boxtree » and « tropical fruit » odours disappeared
Passion fruit aroma
Aroma of young botrytized sweet wines
Cysteinylated precursors to typical aroma of Sauvignon wines
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Starkenmann C.; Flavour Fragr. J. 2008, 23, 369
VI. Sulfur in the food industry
Sulfur compounds in wine
→ 5 families: thiols, sulfides, polysulfides, thioesters, heterocycles
→ 2 categories: boiling point below or above 90 °C (volatile compounds or less)
→ Produced by 2 main processes:
 enzymatic:
degradation of sulfur-containing amino-acids
fermentation
metabolism of sulfur-containing pesticides
 non-enzymatic: photochemical, thermal, chemical reactions during
winemaking and storage
→ Role of SO2: antibiotic and antioxydant (« contains sulfites »; up to 10mg/L)
→ Reactions most studied: those catalyzed by light and producing unpleasant flavours
called « light tastes » or « reduced tastes »
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Guasch J.; J. Chromath. A 2000, 881, 569
VI. Sulfur in the food industry
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Guasch J.; J. Chromath. A 2000, 881, 569
VI. Sulfur in the food industry
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VI. Sulfur in the food industry
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VI. Sulfur in the food industry
Sulfur compounds in wine
 In general, aromatic contributions of the above compounds considered detrimental
to wine quality
→ cabbage, garlic, onion, rubber…
 Some sulfur compounds contribute actively and are typical to some wine aromas
→ strawberry
→ box tree
→ passion fruit
→ cooked leeks
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Guasch J.; J. Chromath. A 2000, 881, 569
VII. A « bad smell » example, just one…
→ Human sweat
Sweat secreted by axillary glands odourless: odoriferous components generated by skin bacteria
A tertiary thiol…
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Starkenmann C.; Flavour Fragr. J. 2008, 23, 369
VIII. Sulfur in perfumes
- Sulfur-containing compounds: some of the strongest odorants
- Perception of odor often depends on:
→ chemical, diastereo- and enantio-purity
→ concentration (unpleasent odor when smelled at high concentration)
▫ ability to trigger different receptor sites in the olfactory bulb of the nose
The cassis/cat example: 4-mercapto-4-methylpentanone 29
> 0.001%: obnoxious tom-cat urine off-odor
(0.4% impurity in paint)
< 0.00001%: natural crisp cassis note
(Sauvignon wines)
Also « Baie rouge » scent (raspberry), box tree, broom, green tea, grapefruit
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Goeke A.; Sulfur reports 2002, 23, 3, 243
VIII. Sulfur in perfumes
 Structure-odor correlations
Free tertiary sulfur group distant of 2-4 Å
of a carbonyl
 Importance of steric bulk around sulfur
group (tertiary mercapto ketones)
 Importance of H bonding
61: no fruity odor
62: less cassis-like than 63
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Goeke A.; Sulfur reports 2002, 23, 3, 243
VIII. Sulfur in perfumes
 Importance of diastereo- and enantio- purity
 Hydrolysis of thioacetates in the mucosa of the olfactory bulb responsible for cassis odor in 38?
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Goeke A.; Sulfur reports 2002, 23, 3, 243
VIII. Sulfur in perfumes
Grapefruit
1982: 1-p-menthene-8-thiol shown to be an extremely potent constituent of grapefruit juice.
Also identified in orange, yuzu and must.
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VIII. Sulfur in perfumes
Passionfruit
Oxane® (perfumery)
62, 63: also in white and red
wines
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Goeke A.; Sulfur reports 2002, 23, 3, 243
VIII. Sulfur in perfumes
Green scents
Fancy « tomato leaves » scent in the perfume « Les Belles »
(Nina Ricci): complex combination of several odorants.
Essential oil of coriander, used in fine fragrances:
« Gucci No. 1 », « Le Jardin d’Amour », « Coriandre » (!)
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Goeke A.; Sulfur reports 2002, 23, 3, 243
VIII. Sulfur in perfumes
Scents of flowers
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Goeke A.; Sulfur reports 2002, 23, 3, 243
VIII. Sulfur in perfumes
The archetypal example: rose oil
Impart naturalness of rose scent perceived when smelling
rose petals to essential rose oil
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Goeke A.; Sulfur reports 2002, 23, 3, 243
VIII. Sulfur in perfumes
Musk odors
- macrocyclic lactones and ketones: core structures found in natural isolates (muscone,
ambrettolide, pentadecanolide)
- quality of musk odor and intensity depends on:
▫ a subtle equilibrium of the ring size and geometry with hydrophobic parts and
hydrogen-bond acceptors
▫ position of sulfur atom / carbonyls (6.9 Å between acceptor sides)
even-nb ring: 1,7-distance
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odd-nb ring: 1,6-distance
Goeke A.; Sulfur reports 2002, 23, 3, 243
VIII. Sulfur in perfumes
Sweet scents
- sweet, caramel-like odor
- generally cyclic dicarbonyl molecule
- planar enol-carbonyl acts as a H-donor/H-acceptor pair of 3 Å distance at the olfactory
receptor site
Maltol
No significant change
Bark of larch trees
Roasted barley
Pines, wines
Furaneol®
Only minor changes
→ Structure of bifunctional unit important (not its chemical character: O vs S)
Goeke A.; Sulfur reports 2002, 23, 3, 243
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Thank you for your attention!
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