10.9 OXIDATION OF THIOLS - Sapling Learning

1 OXIDATION OF THIOLS471of the NAD|molecule. That is, the deuterium in the product NADD (color) occupies the po-sition above the plane of the page. This result and the principle of microscopic reversibility(Sec. , p. 171) require that if acetaldehyde and the NADD stereoisomer shown on theright of Eq. were used as starting materials and the reaction run in reverse, only the deu-terium should be transferred to the acetaldehyde, and (R)-1-deuterioethanol should be , Eq. canbe run in reverse, and the experimental result is as predicted. No matterhow many times the reaction runs back and forth, the H and the D on both the ethanol and theNADD molecules are never scrambled ; they maintain their respective stereochemical posi-tions. Because the R-group in NADH contains asymmetric carbons (Fig.)

2 , p. 462), the twoCH2hydrogens in NADH are in fact diastereotopic;they are distinguished not only by the en-zyme, but also in the absence of the enzyme (at least in principle), although without the en-zyme they might not be distinguished as In each of the following cases, imagine that the two reactants shown are allowed to react inthe presence of alcohol dehydrogenase. Tell whether the ethanol formed is chiral. If theethanol is chiral, draw a line-and-wedge structure of the enantiomer that is formed.(a)(b) OF THIOLSSome of the chemistry of THIOLS is closely analogous to the chemistry of alcohols because sul-fur and oxygen are in the same group of the periodic table. For OXIDATION reactions, however,this similarity disappears. OXIDATION of an alcohol (Sec.

3 Occurs at the carbonatom bear-ing the LOH group. However, OXIDATION of a thiol takes place at the sulfur. Although sulfur analogs of aldehydes,ketones, and carboxylic acids are known, they are notobtained by the simple OXIDATION ofthiols:Some OXIDATION products of THIOLS are given in Fig. (p. 472). The most commonly oc-curring OXIDATION products of THIOLS are disulfides and sulfonic acids (boxed in the figure). Thesame OXIDATION -number calculation used for carbon (Sec. ) can be applied to oxidationat How many electrons are involved in the OXIDATION of 1-propanethiol to each of the follow-ing compounds? (See Fig. for the detailed structures of these compounds.)(a)1-propanesulfonic acid, CH3CH2CH2SO3H(b) 1-propanesulfenic acid, CH3CH2CH2 SOHPROBLEM( )ARCH2 SHRCHSLRCOLSH,SLRCSLOHS oxidationoxidation( )ARCH2 OHRCO2 HRCHO oxidationoxidationDCOH3C+LLSHDCONH2R"MN1 DCOH3C+LLSHDCONH2R" 12/5/08 1:34 PM Page 471472 CHAPTER 10 THE CHEMISTRY OF ALCOHOLS AND THIOLSM ultiple OXIDATION states are common for elements in periods of the periodic table beyondthe second.

4 The various OXIDATION products of THIOLS exemplify the multiple OXIDATION statesavailable to sulfur. The Lewis structures of some derivatives require either more than eight elec-trons or separation of formal charge. Consider, for example, the structure of a sulfonic acid:Sulfur can accommodate more than eight valence electrons because, in addition to its occu-pied 3sand 3porbitals, it has unoccupied 3dorbitals of relatively low energy (Fig. , p. 30).The overlap of an oxygen electron pair in a sulfonic acid with a sulfur 3dorbital is shown inFig. ; this is essentially an orbital picture of the SAO double bond. Notice that much ofthe sulfur 3dorbital is directed away from the oxygen 2porbital; thus, this additional bonding,although significant, is not very strong.

5 This is why the charge-separated resonance structurein Eq. has some acids are formed by the vigorous OXIDATION of THIOLS or disulfides with KMnO4ornitric acid (HNO3).Recall that sulfonate esters (Sec. ) are derivatives of sulfonic acids; other sulfonic acidchemistry is considered in Chapters 16 and THIOLS spontaneously oxidize to disulfides merely on standing in air (O2). THIOLS canalso be converted into disulfides by mild oxidants such as I2in base or Br2in CCl4:( )( )ethanethioldiethyl disulfide(nearly quantitative yield)2C2H5 SHBr2+C2H5 SSC2H52 HBr+L2 CH3(CH2)4SH2 NaOHI2++CH3(CH2)4S(70% yield)S(CH2)4CH32H2O2 NaI++L( )SHCH3CH2CH2CH21-butanethiol1-butanesulf onic acid (72 96% yield)conc. HNO3 LSO3 HCH3CH2CH2CH2L( )3333LL""SS22 ROH2|_SO22O_3333 LLROHSO22 Othe octet structure has charge separationthe uncharged structure has12 electrons around sulfurR SLL121R SHL21thiolOHR SLL1221 OHOsulfinicacidsulfonicacidsulfenicacidS 33R SLL21 OHOSS33O33R R SLLL21disulfideS21 Increasing sulfur OXIDATION levelFigure OXIDATION of THIOLS can give several possible products.

6 Of these, disulfides and sulfonic acids(boxed) are the most 12/5/08 1:34 PM Page OXIDATION OF THIOLS473A reaction like Eq. can be viewed as a series of SN2 reactions in which halogen and sul-fur are attacked by thiolate-anion nucleophiles.( )( )( )When THIOLS and disulfides are present together in the same solution, an equilibrium amongthem is rapidly established. For example, if ethanethiol and dipropyl disulfide are combined,they react to give a mixture of all possible THIOLS and disulfides: THIOLS and sulfides are very important in biology. Many enzymes contain thiol groups thathave catalytically essential functions, and disulfide bonds in proteins help to stabilize theirthree-dimensional structures (Sec. ). rates of the reactions in Eqs. b are increased when the thiol is ionized by a basesuch as sodium ethoxide.

7 Suggest a mechanism for Eq. that is consistent with this ob-servation, and explain why the presence of base makes the reaction ( )ethanethiolethyl propyl disulfideCH3CH2 SHCH3CH2 SSCH2CH2CH3+Lpropanethioldiethyl disulfideCH3CH2CH2 SHCH3CH2 SSCH2CH3+L( )ethanethioldipropyl disulfideCH3CH2 SHCH3CH2CH2 SSCH2CH2CH3+Lpropanethiolethyl propyl disulfideCH3CH2CH2 SHCH3CH2 SSCH2CH2CH3+LLRR+S22S22LR__S223I2233 LLLRS22LI223LR+S22 LLR__S223I223I2233LI223I223 LLRHOH+_S22223 LRH2O+_S222331oxygen 2p orbitalsulfur 3d orbitalROSHOO54 LLLLLLLLLLHOF igure in the higher OXIDATION states of sulfur involves sulfur 3dorbitals. Wave peaks and troughsare shown in blue and green, respectively. In a sulfonic acid (RSO3H; see Eq. ), an electron pair on oxygen over-laps with one of several sulfur 3dorbitals.

8 The overlap is indicated with colored lines. Notice that this overlap is notvery efficient because the orbitals have different sizes and because half of the sulfur 3dorbital is directed awayfrom the 12/5/08 1:34 PM Page 473