Special Topic Sulfur Going beyond the bad smell… Gaëlle Mingat 10/10/12 1.

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Special Topic

Sulfur

Going beyond the bad smell…

Gaëlle Mingat10/10/12

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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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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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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


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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

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I. General properties Essential element for life

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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


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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- 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)


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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


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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


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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



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Corey-Chaykovsky reaction: JACS 1965, 87 (6), 1353



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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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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


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



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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



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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)


Aggarwal


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IV. Chiral sulfur


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IV. Chiral sulfur


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IV. Chiral sulfur


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IV. Chiral sulfur

http://www.chemtube3d.com/Oppolzer.html


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IV. Chiral sulfur


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Stuart Warren’s work; preliminary observation


Warren S.; Phosphorous, Sulfur and Silicon 1999, 153-154, 59

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D. House, S. Warren: stereospecificity in the migration of « SPh »


Secondary OH = LGPrimary OH = Nu

Secondary OH = LGPrimary OH no more a Nu


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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



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Kinetic resolution of racemic and enolisable 2-PhS aldehydes



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· 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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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


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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

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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


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VII. A « bad smell » example, just one…

→ Human sweat

A tertiary thiol…

Sweat secreted by axillary glands odourless: odoriferous components generated by skin bacteria


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- 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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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


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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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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.

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VIII. Sulfur in perfumesPassionfruit

Oxane® (perfumery)

62, 63: also in white and red wines


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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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Scents of flowers


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The archetypal example: rose oil

Impart naturalness of rose scent perceived when smelling rose petals to essential rose oil


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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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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

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Thank you for your attention!

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.