Special Topic Sulfur Going beyond the bad smell… Gaëlle Mingat 10/10/12 1.
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Transcript of Special Topic Sulfur Going beyond the bad smell… Gaëlle Mingat 10/10/12 1.
2
Sulfur, going beyond the bad smell…Overview
10/10/12
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
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I. General properties- abundant, multivalent non-metal- cyclic octatomic molecule: S8
Bright yellow solid
- Either an oxidant or a reducing agent
- Found in nature as the pure element, sulfide (S2-) and sulfate (SO4
2-) minerals
Melting point: 115.21 °C, blood-red liquidBurns with a blue flame better observed in the dark
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I. General properties
Carrying sulfur blocks from a volcano, Indonesia
- 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
HydrodesulfurizationR-S-R + 2H2 → 2 R-H + H2S
Conversion of hydrogen sulfide in elemental sulfur via the Claus process3 O2 + 2 H2S → 2 SO2 + 2 H2OSO2 + 2 H2S → 3 S + 2 H2O
World production in 2011: 69 M tones→ China (9.6), US (8.8), Canada (7.1), Russia (7.1)
Stockpiles of elemental sulfur recovered from hydrocarbons,
Alberta, Canada
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 pmS: r = 104.9 pm
C-O: 355-380 kJ/molC-S: 255 kJ/mol
C=O: 678 kJ/molC=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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→ electron affinities, ionization potentials, bond energies
C-S bond: polarization not pronounced Ionic character lessened as compared to oxygen counterparts
(hydrogen bonding less important)
Sanderson: «compactness » of an atom’s electron cloud→ Polarizability of S
Aromaticity: furan (Eres = 75kJ/mol) < thiophene < benzene (Eres = 113 kJ/mol)
SO
I. General propertiesElectronegativities
Schaumann E.; Top Curr. Chem. 2007, 274:1-34 (DOI 10.1007/128_2006_105)
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I. General properties Essential element for life
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OH
O
NH2
SHS OH
O
NH2
Cysteine
Cystine(dehydrogenated cysteine)
MethionineGlutathione : antioxydant
(Cysteine/Glycine/Glutamate)
Disulfide bonds : mechanical strength, insolubility of keratin (hair, outer skin, feathers) and pungent odor when burned
Thioester acetyl coenzyme A
8
I. General properties Essential element for life
8
Thiamine (vitamin B1)Umpolung chemistry in nature
Penicillin core structure
« S-adenosylmethionine »: Nature’s iodomethane or diazomethane equivalent
Biotin (vitamin H)
Sulfanilamide (sulfa drug)
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Thiols: R-SH Sulfides: R-S-R
Sulfoxides Sulfones Sulfonic acids
Sulfimides Sulfoximides Sulfonediimides
Thiocarbonyls: thioamides
O
SR1 R2
O
SR1 R2O
O
SR
OOH
N
SR1 R2
R3 N
SR1 R2O
R3N
SR1 R2N
R3
R4
S
R1 N
R2
R3
O
SR OH
Sulfinic acids
R1 S NR3
R2S
O
NR1
R3
R2R1 S
O
O
NR3
R2
Sulfonamides (sulfa drugs)
Sulfinamides Sulfenamides
I. General properties
Sulfenic acids
R S OH
Important chemical functionalities
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S-nitrosothiols Isothiocyanates
Sulfonium, oxosulfonium ion Sulfonium, oxosulfonium ylide
R S N O R N C S
S
R1 R2
O
Sulfines
Thiocyanates
R S C N
[R3S]+
O
SR1 R2R3
S CR1
R2
R3
R4
S CR3
R4R2
R1
O
I. General properties Important chemical functionalities
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II. Some name reactions involving sulfur
- 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)
- Sulfur as a reducing agent→ NaHSO3, Na2SO3, Na2S2O3, Na2S·9H2O, SOCl2, SO2...→ Me2S in ozonolysis to prevent further oxidation of products (still used??)
- Lawesson’s reagent: from a ketone to a thioketone→ Enones, esters, lactones, amides, lactams, quinones
Kürti L., Czako B.; Strategic Applications of Named Reactions in Organic Synthesis (2005)
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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)
Kürti L., Czako B.; Strategic Applications of Named Reactions in Organic Synthesis (2005)
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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
Kürti L., Czako B.; Strategic Applications of Named Reactions in Organic Synthesis (2005)
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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
Kürti L., Czako B.; Strategic Applications of Named Reactions in Organic Synthesis (2005)
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→ 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
II. Some name reactions involving sulfur
Kürti L., Czako B.; Strategic Applications of Named Reactions in Organic Synthesis (2005)
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III. Sulfur ylides and the Corey-Chaykovsky reaction
Schaumann E.; Top Curr. Chem. 2007, 274:1-34 (DOI 10.1007/128_2006_105)
17
Corey-Chaykovsky reaction: JACS 1965, 87 (6), 1353
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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Enantio- and diastereocontrol in sulfur ylides-mediated epoxidations: Aggarwal’s work
III. Sulfur ylides and the Corey-Chaykovsky reaction
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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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
III. Sulfur ylides and the Corey-Chaykovsky reaction
Aggarwal V.; Chem. Commun. 2003, 2644
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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
III. Sulfur ylides and the Corey-Chaykovsky reaction
Aggarwal V.; Chem. Commun. 2003, 2644
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Control of enantioselectivity
1) Formation of a single diastereoisomeric sulfonium ylide2) High level of control of ylide conformation3) High level of control in face selectivity of the ylide4) Non-reversibility of the anti-betaine formation
III. Sulfur ylides and the Corey-Chaykovsky reaction
Aggarwal V.; Chem. Commun. 2003, 2644
23
Control of enantioselectivity: effect of protic solvents
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)
III. Sulfur ylides and the Corey-Chaykovsky reaction
Aggarwal
Aggarwal V.; Chem. Commun. 2003, 2644
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IV. Chiral sulfur
http://www.chemtube3d.com/Oppolzer.html
Schaumann E.; Top Curr. Chem. 2007, 274:1-34 (DOI 10.1007/128_2006_105)
29
Stuart Warren’s work; preliminary observation
V. Sulfur migration in organic synthesis
Warren S.; Phosphorous, Sulfur and Silicon 1999, 153-154, 59
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D. House, S. Warren: stereospecificity in the migration of « SPh »
V. Sulfur migration in organic synthesis
Secondary OH = LGPrimary OH = Nu
Secondary OH = LGPrimary OH no more a Nu
Warren S.; Phosphorous, Sulfur and Silicon 1999, 153-154, 59
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Competition between 2 hydroxyl groups
Is it possible to control which OH leaves, which acts as a Nu and where it attacks??
Primary OH = LGSPh = Nu
Primary OH = LGSecondary OH = Nu
V. Sulfur migration in organic synthesis
Warren S.; Phosphorous, Sulfur and Silicon 1999, 153-154, 59
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Kinetic resolution of racemic and enolisable 2-PhS aldehydes
V. Sulfur migration in organic synthesis
Warren S.; Phosphorous, Sulfur and Silicon 1999, 153-154, 59
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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→ highly important for flavours and aromas Goeke A.; Sulfur reports 2002, 23, 3, 243
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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 industryRole 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
Starkenmann C.; Flavour Fragr. J. 2008, 23, 369
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VI. Sulfur in the food industryRole of cysteine and cysteine-S conjugates as odour precursors
Wine and passion fruit
Wine treated with copper sulfate → « boxtree » and « tropical fruit » odours disappeared
Aroma of young botrytized sweet wines
Passion fruit aroma
Cysteinylated precursors to typical aroma of Sauvignon wines
Starkenmann C.; Flavour Fragr. J. 2008, 23, 369
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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
fermentationmetabolism 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 »
Guasch J.; J. Chromath. A 2000, 881, 569
41
VI. Sulfur in the food industry
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
S
O
SH
O
OSH OHS
HO
SH
Sulfur compounds in wine
Guasch J.; J. Chromath. A 2000, 881, 569
42
VII. A « bad smell » example, just one…
→ Human sweat
A tertiary thiol…
Sweat secreted by axillary glands odourless: odoriferous components generated by skin bacteria
Starkenmann C.; Flavour Fragr. J. 2008, 23, 369
43
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
Goeke A.; Sulfur reports 2002, 23, 3, 243
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VIII. Sulfur in perfumes
Importance of steric bulk around sulfur group (tertiary mercapto ketones)
· Structure-odor correlationsFree tertiary sulfur group distant of 2-4 Å of a carbonyl
Importance of H bonding61: no fruity odor62: less cassis-like than 63
Goeke A.; Sulfur reports 2002, 23, 3, 243
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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?
Goeke A.; Sulfur reports 2002, 23, 3, 243
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VIII. Sulfur in perfumesGrapefruit
1982: 1-p-menthene-8-thiol shown to be an extremely potent constituent of grapefruit juice.
Also identified in orange, yuzu and must.
47
VIII. Sulfur in perfumesPassionfruit
Oxane® (perfumery)
62, 63: also in white and red wines
Goeke A.; Sulfur reports 2002, 23, 3, 243
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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 » (!)
Goeke A.; Sulfur reports 2002, 23, 3, 243
50
VIII. Sulfur in perfumes
The archetypal example: rose oil
Impart naturalness of rose scent perceived when smelling rose petals to essential rose oil
Goeke A.; Sulfur reports 2002, 23, 3, 243
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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-distanceodd-nb ring: 1,6-distance Goeke A.; Sulfur reports 2002, 23, 3, 243
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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
MaltolBark of larch treesRoasted barleyPines, wines
No significant change Furaneol® Only minor changes
→ Structure of bifunctional unit important (not its chemical character: O vs S)Goeke A.; Sulfur reports 2002, 23, 3, 243