In a blatant plug for the Reagent G

In a blatant plug for the Reagent Guide and the Reagents App for iPhone, each Friday I profile a different reagent that is commonly encountered in Org 1/ Org 2.

If there’s one thing you learn how to do well in Org 1, it’s make alcohols. Let’s count the ways: hydroboration, acid-catalyzed hydration, oxymercuration for starters, and then substitution of alkyl halides with water or HO(–). If you want to extend it even further, there’s dihydroxylation (to make diols) using OsO4 or cold KMnO4, and even opening of epoxides under acidic or basic conditions to give alcohols.

There’s just one issue here and it comes up once you try to use alcohols in synthesis. Let’s say you want to use that alcohol in a subsequent substitution step, getting rid of the HO(–) and replacing it with something else. See any problems with that? Remember that good leaving groups are weak bases – and the hydroxide ion, being a strong base, tends to be a pretty bad leaving group.

So what can we do?

What you want to do is convert the alcohol into a better leaving group. One way is to convert the alcohol into a sulfonate ester – we talked about that with TsCl and MsCl. Today I’m going to talk about a second approach: converting alcohols into alkyl chlorides with thionyl chloride (SOCl2). This is a useful reaction, because the resulting alkyl halides are versatile compounds that can be converted into many compounds that are not directly accessible from the alcohol itself.





If you take an alcohol and add thionyl chloride, it will be converted into an alkyl chloride. The byproducts here are hydrochloric acid (HCl) and sulfur dioxide (SO2).
[NOTE added later: there are significant differences in how this reaction is taught at different schools. Consult your instructor to be 100% sure that this applies to your course]. See post here





There’s one important thing to note here: see the stereochemistry? It’s been inverted.*(white lie alert – see below) That’s an important difference between SOCl2 and TsCl, which leaves the stereochemistry alone. We’ll get to the root cause of that in a moment, but in the meantime, can you think of a mechanism which results in inversion of configuration at carbon?

As an extra bonus, thionyl chloride will also convert carboxylic acids into acid chlorides (“acyl chlorides”). Like alcohols, carboxylic acids have their limitations as reactants: the hydroxyl group interferes with many of the reactions we learn for nucleophilic acyl substitution (among others). Conversion of the OH into Cl solves this problem.



So how does it work?

As you might have guessed, conversion of alcohols to alkyl halides proceeds through a substitution reaction – specifically, an SN2 mechanism. The first step is attack of the oxygen upon the sulfur of SOCl2, which results in displacement of chloride ion. This has the side benefit of converting the alcohol into a good leaving group: in the next step, chloride ion attacks the carbon in SN2 fashion, resulting in cleavage of the C–O bond with inversion of configuration. The HOSCl breaks down into HCl and sulfur dioxide gas, which bubbles away.



The mechanism for formation of acid chlorides from carboxylic acids is similar.



Real life tips

Like many sulfur-containing compounds, thionyl chloride is noseworthy for its pungent smell. Thionyl chloride has a nauseating sickly-sweet odor to it that imprints itself forever upon your memory . One accident that occurred during my time as a TA involved a student dropping a flask with 5 mL of thionyl chloride into a rotovap bath outside the fume hood. The cloud of SO2 and HCl that formed cleared the teaching lab for half an hour, so you can imagine what thionyl chloride would do if exposed to the moisture in your lungs. Treat with caution, just as you would if you were working with phosgene.

*Here’s the white lie. Although it’s generally taught in Org 1/ Org 2 that SOCl2 leads to 100% inversion of configuration, in reality it’s not always that simple. Inversion of configuration with SOCl2 is very solvent dependent. Depending on the choice of solvent, one can get either straight inversion, or a mixture of retention and inversion. For the purposes of Org 1 and Org 2, most students can ignore this message. For more details see March’s Advanced Organic Chemistry

P.S. You can read about the chemistry of SOCl2 and more than 80 other reagents in undergraduate organic chemistry in the “Organic Chemistry Reagent Guide”, available here as a downloadable PDF. The Reagents App is also available for iPhone, click on the icon below!

Results (English) 1:

In a blatant plug for the Reagent Guide and the Reagents App for iPhone, each Friday I profile a different reagent that is commonly encountered in Org 1/2 Org. If there's one thing you learn how to do well in Org 1, it's make alcohols. Let's count the ways: hydroboration, oxymercuration, acid-catalyzed hydration for starters, and then substitution of alkyl halides with water or COUGHING (-). If you want to extend it even further, there's dihydroxylation (to make diols) using OsO4 or KMnO4 cold, and even opening of epoxides under acidic or basic conditions to give alcohols.There's just one issue here and it comes up once you try to use alcohols in synthesis. Let's say you want to use that alcohol in a subsequent substitution step, getting rid of the COUGH (-) and replacing it with something else. See any problems with that? Remember that good leaving groups are weak bases-and the hydroxide ion, being a strong base, which tends to be a pretty bad leaving group.So what can we do?What you want to do is convert the alcohol into a better leaving group. One way is to convert the alcohol into a sulfonate ester-we talked about that with TsCl and MsCl. Today I'm going to talk about a second approach: converting alcohols into alkyl chlorides, thionyl chloride (SOCl2) with. This is a useful reaction, because the resulting alkyl halides are versatile compounds that can be converted into many compounds that are not directly accessible from the alcohol itself. If you take an alcohol thionyl chloride and add, it will be converted into an alkyl chloride. The byproducts here are hydrochloric acid (HCl) and sulfur dioxide (SO2).[NOTE added later: there are significant differences in how this reaction is self-taught at different schools. Consult your instructor to be 100% sure that this applies to your course]. See post here There's one important thing to note here: see the stereochemistry? It's been inverted.* (white lie alert – see below) that's an important difference between SOCl2 and TsCl, which leaves the stereochemistry alone. We'll get to the root cause of that in a moment, but in the meantime, can you think of a mechanism which results in inversion of configuration at carbon?As an extra bonus, thionyl chloride will also convert carboxylic acids into acid chlorides ("acyl chlorides"). Like alcohols, carboxylic acids have their limitations as reactants, the hydroxyl group interferes with many of the reactions we learn for nucleophilic acyl substitution (among others). Conversion of the OH into Cl solves this problem.So how does it work?As you might have guessed, the conversion of alcohols to alkyl halides proceeds through a substitution reaction-specifically, an SN2 mechanism. The first step is attack of the oxygen upon the sulfur of SOCl2, which results in displacement of the chloride ion. This has the side benefit of converting the alcohol into a good leaving group: in the next step, the chloride ion attacks the carbon in SN2 fashion, resulting in cleavage of the C-O bond with inversion of configuration. The HOSCl breaks down into HCl and sulfur dioxide gas, which bubbles away.The mechanism for formation of acid chlorides from carboxylic acids is similar.Real life tipsLike many sulfur-containing compounds, thionyl chloride is noseworthy along with for its pungent smell. Thionyl chloride has a nauseating sickly-sweet odor to it that imprints itself forever upon your memory. One accident that occurred during my time as a TA involved a student dropping a flask with 5 mL of thionyl chloride into a rotovap bath outside the fume hood. The cloud of SO2 and HCl that well-formed cleared the teaching lab for half an hour, so you can imagine what thionyl chloride would do if exposed to the moisture in your lungs. Treat with caution, just as you would if you were working with phosgene.* Here's the white lie. Although it's generally self-taught in Org 1/2 Org that SOCl2 leads to 100% inversion of configuration, in reality it's not always that simple. Inversion of configuration with SOCl2 is very solvent dependent. Depending on the choice of solvent, one can get either straight inversion, or a mixture of retention and inversion. For the purposes of 1 Org and Org 2, most students can ignore this message. For more details see March's Advanced Organic Chemistry P.s. You can read about the chemistry of SOCl2 and more than 80 other reagents in undergraduate organic chemistry in the "Organic Chemistry Reagent Guide", available here as a downloadable PDF. The Reagents App is also available for the iPhone, click on the icon below!

Results (English) 2:

In a blatant plug for the Reagent Guide and the Reagents App for iPhone, each Friday I profile a different reagent nằm commonly gặp in Org 1 / Org 2. If there's one thing you learn how 'to ​​do well in Org 1, it's make alcohols . Let's count the Ways: hydroboration, acid-catalyzed hydration, oxymercuration for starters, and then substitution of alkyl halides with water or HO (-). If you want to extend it thậm Further, there's dihydroxylation (to make diols) using OsO4 or cold KMnO4, and thậm opening of epoxides under acidic or basic conditionsEND_SPAN to give alcohols. There's just one issue here and it Comes up once you try to use alcohols in synthesis. Let's say you want to use alcohol in a subsequent substitution mà step, getting rid of the HO (-) and replacing it with something else. See any problems with that? Remember mà good Leaving groups are weak bases - and the hydroxide ion, being a strong base, tends to be a pretty bad Leaving group. So what can WE DO? What is muốn by converting the alcohol Into Leaving a better group. One way is to convert the alcohol ester sulfonate Into a - we Talked About mà with TsCl and MsCl. Today I'm going to talk about a second approach: converting alcohols with thionyl chloride Into alkyl chlorides (SOCl2). This is a reaction ích, alkyl halides vì quả versatile compounds are converted Into có thể many compounds That Are Not Directly accessible from the alcohol chính nó. If you take an alcohol and thionyl chloride added, it will be converted Into an alkyl chloride. The hydrochloric acid byproducts are here (HCl) and sulfur dioxide (SO2). [NOTE added later: there are the significant Hiệu in how this reaction is Taught at khác schools. Consult của to be 100% sure instructor mà this applies to của course]. See post here There's one thing to note here Important: see the stereochemistry? It's been inverted. * (White cork alert - see below) That's an Important difference the between SOCl2 and TsCl mà leaves the stereochemistry alone. We'll get to the root-cause of mà in a moment, but in the meantime, can you think of a mechanism results in inversion of configuration mà at carbon? As an extra bonus, thionyl chloride will convert carboxylic acids Into cũng acid chlorides ( "acyl chlorides"). Like alcohols, carboxylic acids as reactants have chúng Limitations: the hydroxyl group interferes with many of the Reactions Nucleophilic acyl substitution for chúng learn (among others). Conversion of the OH Cl Into this solves problem. So how does it work? As you might, have guessed, conversion of alcohols to alkyl halides proceeds through a substitution reaction - specifically, an SN2 mechanism. The first step is attack of the oxygen upon the sulfur of SOCl2, mà results in displacement of chloride ion. This has the side Benefit of converting the alcohol group để vào good: in the next step, chloride ion attacks the carbon in SN2 fashion, in cleavage of the C quả-O bond with inversion of configuration. The HOSCl breaks down hydrogen chloride and sulfur dioxide gas Into mà bubbles away. The mechanism for formation of acid chlorides from carboxylic acids is similar. Real life tips sulfur-containing compounds Like many, thionyl chloride is noseworthy for its pungent smell. Thionyl chloride sickly-sweet has a nauseating odor to it mà chính nó imprints upon của memory forever. One accident occurred khi có my time as a TA INVOLVED a student dropping a flask with 5 mL of thionyl chloride Into a fume hood the rotovap bath outside. The cloud of SO2 and HCl formed mà cleared the teaching lab for half an hour, than you can imagine what thionyl chloride would do if exposed to the moisture in your Lungs. Treat with caution, just as you would if you were working with phosgene. * Here's the white lie. Although it's Generally Taught in Org 1 / Org 2 mà SOCl2 leads to inversion of configuration 100%, in reality it's not always simple mà. Inversion of configuration with SOCl2 is very solvent dependent. On the choice of solvent phụ thuộc, one can get straight hoặc inversion, or a mixture of retention and inversion. For the Purposes of Org Org 1 and 2, most Students can ignore this message. For more details see March's Advanced Organic Chemistry PS You can read about the chemistry of SOCl2 and more carbon 80 in undergraduate organic chemistry reagents other in the "Organic Chemistry Reagent Guide", available here as a downloadable PDF. The Reagents App is available for iPhone cũng, click on the icon below!