Comments on: Nucleophilicity of Amines https://www.masterorganicchemistry.com/2018/05/07/nucleophilicity-of-amines/ Wed, 21 Sep 2022 02:31:14 +0000 hourly 1 https://wordpress.org/?v=6.6.2 By: James Ashenhurst https://www.masterorganicchemistry.com/2018/05/07/nucleophilicity-of-amines/#comment-634569 Wed, 03 Aug 2022 21:52:17 +0000 https://www.masterorganicchemistry.com/?p=11345#comment-634569 In reply to Hippolyte DORY.

Yes, it will definitely work, for example look up the synthesis of hexamethyldisilazane. https://en.wikipedia.org/wiki/Bis(trimethylsilyl)amine

]]> By: Hippolyte DORY https://www.masterorganicchemistry.com/2018/05/07/nucleophilicity-of-amines/#comment-620835 Wed, 16 Feb 2022 12:08:06 +0000 https://www.masterorganicchemistry.com/?p=11345#comment-620835 Hello,

I am trying to get Si-Cl and -NH-Si- to react together in order to form Si-N-Si + HCl. I would like to know if the NH is nucleophilic enough to have the reaction between the electrophilic Si-Cl and the amine. this reaction works with Si-OH and Si-Cl so I would like to transpose it to amine counterpart.

]]> By: James Ashenhurst https://www.masterorganicchemistry.com/2018/05/07/nucleophilicity-of-amines/#comment-607240 Tue, 19 Oct 2021 16:07:36 +0000 https://www.masterorganicchemistry.com/?p=11345#comment-607240 In reply to Guillaume Reynard.

Hi Guillaume – nitriles or cyanide ion? Nitriles themselves are really bad nucleophiles and will only work in Ritter-type reactions where they are reacting with an extremely good electrophile.
Think about hybridization. Acetylene C-H is more acidic than alkanes because sp-hybridization stabilizes negative charge. Likewise the nitrogen of nitriles, being sp-hybridized makes that nitrogen lone pair very stable (and a very poor base / nucleophile) relative to the sp3 hybridized nitrogen in amines.

]]> By: Guillaume Reynard https://www.masterorganicchemistry.com/2018/05/07/nucleophilicity-of-amines/#comment-607106 Mon, 18 Oct 2021 20:54:41 +0000 https://www.masterorganicchemistry.com/?p=11345#comment-607106 Hi James, thank you for a really interesting topic !

I’m currently working with nitriles, and I’ve been unable to find a good quantification method of their nuclophilicity, weither looking into Mayr’s of Hammet’s quantifying methods. Do you know if there’s any ?

Thank you in advance !

Guillaume

]]> By: James Ashenhurst https://www.masterorganicchemistry.com/2018/05/07/nucleophilicity-of-amines/#comment-558696 Wed, 24 Jul 2019 02:28:41 +0000 https://www.masterorganicchemistry.com/?p=11345#comment-558696 In reply to Ryad.

How do you know it’s going to do a substitution and not elimination?

]]> By: Ryad https://www.masterorganicchemistry.com/2018/05/07/nucleophilicity-of-amines/#comment-558595 Mon, 22 Jul 2019 05:39:26 +0000 https://www.masterorganicchemistry.com/?p=11345#comment-558595 I am stuck with carrying out a nucleophilic substitution reaction of triethylamine with chloride atoms in Polyvinyl chloride. Could you gove some ideas please?

]]> By: James Ashenhurst https://www.masterorganicchemistry.com/2018/05/07/nucleophilicity-of-amines/#comment-558279 Mon, 15 Jul 2019 17:29:29 +0000 https://www.masterorganicchemistry.com/?p=11345#comment-558279 In reply to Richard Suderman.

The pKa values you cite are for the conjugate acids of the amines, not the amines themselves. pH 7.2 is a neutral solution. The neutral amines will not be protonated to any appreciable extent until pH4 or below, and even then they will be in equilibrium.

]]> By: Richard Suderman https://www.masterorganicchemistry.com/2018/05/07/nucleophilicity-of-amines/#comment-558081 Thu, 11 Jul 2019 15:08:45 +0000 https://www.masterorganicchemistry.com/?p=11345#comment-558081 Hi James,
I routinely conjugate proteins via their primary amines to substrates and tags containing NHS esters at pH 7.2. It just occurred to me that at pH 7.2 the primary amine should be protonated to R-NH3(+), since the pKa of primary amines in proteins is approximately 9 and 10.5, for alpha and epsilon amines, respectively. How can the positively charged, protonated amine act as a nucleophile?? Thanks in advance, and I love reading your page!
Rich

]]> By: James Ashenhurst https://www.masterorganicchemistry.com/2018/05/07/nucleophilicity-of-amines/#comment-553001 Tue, 16 Apr 2019 20:15:21 +0000 https://www.masterorganicchemistry.com/?p=11345#comment-553001 In reply to Sam.

Right. The nucleophilicity will certainly be solvent dependent. If you look at the tables from Mayr they all specify solvent and only should be compared directly when the numbers were obtained in the same solvent. You will also note that tertiary amines don’t have good nucleophilicity numbers in water, because they’re just not very soluble in polar solvents.

I don’t have a good clear answer for you regarding trends. Hydrogen bonding is one factor, but so is the increased electron density that comes with additional alkyl groups. It’s not a one-dimensional quantity, it’s multivariable. Making a measurement is the best way to sort it all out.

]]> By: Sam https://www.masterorganicchemistry.com/2018/05/07/nucleophilicity-of-amines/#comment-552945 Tue, 16 Apr 2019 13:46:45 +0000 https://www.masterorganicchemistry.com/?p=11345#comment-552945 Very good explanation but could you clarify the influence of H2O in section about quantifying nucleophilicity? Water is polar protic solvent so why should the nucleophilicity of the amines (NH3 vs secondary vs tertiary) increase in water? Shouldn’t it be the other way around due to H-bonding?

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