Subject: SUMMARY: Secondary amines

From: Jose Javier Cuadrado <[email-masked]>
Date: Wed, 07 Aug 2002 12:29:44 +0200

Thanks to all who answer my question.

My question was:

   * Hi to all

            I am working with a molecule that contains a secondary amine

group. Its sustituents are:

        +a benzyl group
        +a phenyl ring

            I would like to know if that NH is a possible hydrogen bond
acceptor. I have not found two much information. Could anybody tell me
any reference about that class of secondary amines and their role as
hydrogen bond acceptors?

            Thanks in advance

The answers Ihave got:

       1. Dick Caldwell wrote:

     A weak one. You need to find a list of pKa's of amines - the
     usual
     advanced organic texts will be a good start. I guess that
     yours will have
     a pKa of about 7, cf. good amine bases (i.e. good H bond
     acceptors) at
     about 11-12.
     good luck, Dick Caldwell

       1. Jeremy Greenwood  wrote

     Hi Jose,

     >
     >
     >             I am working with a molecule that contains a
     secondary amine
     > group. Its sustituents are:
     >
     >
     >         +a benzyl group
     >         +a phenyl ring
     >
     i.e. :N(H)(CH2Ph)(Ph) <<-->> (H)N+(H)(CH2Ph)(Ph)

     >             I would like to know if that NH is a possible
     hydrogen bond
     > acceptor. I have not found two much information. Could
     anybody tell me
     > any reference about that class of secondary amines and their
     role as
     > hydrogen bond acceptors?

     (assuming you're interested in hydrogen bond acceptors in the
     context of biological activity)

     If it's protonated, it's potentially a double hydrogen bond
     donor
     If it's neutral, it's potentially a single hydrogen bond donor

     and single hydrogen bond acceptor.

     The pKa is around 10, so it's most likely a potential double
     hydrogen bond donor at physiogical pH. Whether or not it is
     protonated
     in a given receptor will depend on the local environment.
     The local environment will also determine how many hydrogen
     bonds
     it participates in, since it's somewhat sterically crowded.
     If it's not protonated, then the receptor environment (and/or
     the rest of the molecule) will determine the chirality of the
     nitrogen, so you can't say anything a priori about which
     direction
     it can donates and accepts in.

     Hope this helps a little,

     Jeremy
     ----------------------------------------------------------------------

     Jeremy Greenwood
     [email-masked]
     Department of Medicinal Chemistry                      bh +45
     35306117
     Royal Danish School of Pharmacy                        fx +45
     35306040
     Universitetsparken 2, DK-2100 Copenhagen, Denmark      ah +45
     32598030
     ----------------------------------------------------------------------

       1. Richard L. wood wrote:

     Hi Jose

     I'm not an expert on this topic.

     That said, as I recall from my undergraduate sophomore
     inorganic chemistry,
     the basicity of amines decreases as you go from
     primary to secondary to tertiary, as the electron withdrawing
     power of the
     R groups pulls the lone pair electrons closer to the nitrogen,

     making it more difficult to donate those electrons to an
     acid.  I would
     think it would make it more difficult to act as an H-bond
     acceptor
     as well.  So I would think that H-bond acceptor strength would
     go ammonia >
     primary amine > secondary amine.

     I hope this helps.

     Richard

       1. Dave Shobe wrote:

     I don't think the benzyl group would make that much
     difference.  (Unlike the
     phenyl group which is known to interact strongly with the
     nitrogen lone
     pair).

     Accordingly, if you can't find a study on N-benzylaniline, a
     study of
     N-methylaniline or N-ethylaniline would probably be close
     enough.

     Hopefully you are in a place with good literature searching
     tools. :-)

     --David Shobe
     Süd-Chemie Inc.
     phone (502) 634-7409
     fax     (502) 634-7724
     email  [email-masked]