Color poster with text, diagrams, tables, and graphs.This study presented the mechanistic implications of the kinetics of competing reactions of N-aryl-4-chloro-1,8-naphthalimides with primary amines.University of Wisconsin--Eau Claire Office of Research and Sponsored Programs; Petroleum Research Fund

La Plante, Kayla A.

McKenney, Ryan K.

English

Minds@University of Wisconsin

NNMe2O O NHNO ONClO OBuNH2BuNH2SO2NH2 SO2NH2Kinetics of competing reactions of N-aryl-4-chloro-1,8-naphthalimides with primary aminesRyan K. McKenney and Kayla A. La Plante (Faculty Mentor: David E. Lewis) Department of Chemistry, University of Wisconsin-Eau Claire, Eau Claire, WI 54702, U.S.A.Conven&onal	  Wisdom	  •  The	  conven&onal	  wisdom	  is	  that	  the	  heterocyclic	  ring	  of	  N-­‐arylnaphthalimides	  is	  resistant	  to	  nucleophilic	  a;ack	  (Stewart,	  Lucifer	  Yellow	  anhydride,	  1981).	  •  Nucleophilic	  a;ack	  on	  the	  heterocyclic	  ring	  was	  successful	  only	  when	  both	  the	  naphthalimide	  ring	  and	  the	  N-­‐aryl	  group	  carried	  two	  strongly	  electron-­‐withdrawing	  sulfonyl	  groups.	  	  •  Subsequent	  finding	  that	  a	  halogen	  at	  the	  4-­‐	  posi&on	  of	  the	  N-­‐alkyl-­‐1,8-­‐naphthalimide	  is	  readily	  displaced	  by	  amine	  nucleophiles.	  Rate	  Constants	  R	   Rate	  Constant	  (min-­‐1)	  m-­‐Cl	   2.65±0.11	  ×	  10–3	  	  p-­‐Br	   1.08±0.12	  ×	  10–3	  	  m-­‐OMe	   3.7±0.6	  ×	  10–4	  	  H	   1.6±0.4	  ×	  10–4	  	  •  A	  Hamme;	  plot	  of	  the	  rate	  constants	  for	  reactants	  with	  subs&tuents	  having	  0.37	  >	  σ	  >	  0	  is	  given	  in	  Figure	  2.	  	  	  •  It	  is	  linear	  (R2=0.994),	  with	  a	  slope	  ρ=+3.35.	  •  This	  is	  consistent	  with	  an	  increase	  in	  the	  electron	  density	  at	  the	  heterocyclic	  nitrogen	  as	  the	  reac&on	  proceeds.	  Hamme;	  Plot	  for	  Reac&on	  (σ≥0)	  Brønsted	  Law	  Plot	  Conclusions	  •  The	  aroma&c	  ring	  on	  the	  heterocyclic	  nitrogen	  is	  essen&al	  for	  this	  reac&on	  (not	  steric	  in	  origin)	  •  Electron-­‐dona&ng	  (amine)	  subs&tuents	  at	  the	  4-­‐	  posi&on	  completely	  suppress	  the	  reac&on.	  •  The	  large	  posi&ve	  slope	  of	  the	  Hamme;	  plot	  is	  consistent	  with	  the	  genera&on	  of	  a	  substan&al	  par&al	  nega&ve	  charge	  on	  the	  nitrogen.	  	  •  When	  the	  same	  reac&on	  takes	  place	  with	  an	  alcohol	  as	  a	  co-­‐solvent	  the	  kine&c	  data	  clearly	  demonstrate	  general	  acid	  catalysis	  of	  the	  reac&on.	  Prepara&on	  	  of	  Dye	  and	  Unexpected	  Reac&vity	  with	  Primary	  Amines	  •  We	  prepared	  the	  N-­‐aryl-­‐4-­‐chloroimide	  3	  by	  hea&ng	  sulfanilamide	  and	  4-­‐chloro-­‐1,8-­‐naphthalic	  anhydride	  (2)	  in	  benzonitrile.	  •  When	  imide	  3	  was	  heated	  in	  hexylamine,	  the	  product	  isolated	  was	  N-­‐hexyl-­‐4-­‐hexylamino-­‐1,8-­‐naphthalimide	  (5).	  	  	  •  Even	  at	  room	  temperature,	  the	  reac&on	  gave	  4-­‐chloro-­‐N-­‐hexyl-­‐1,8-­‐naphthalimide	  (6).	  •  	  This	  shows	  that	  the	  subs&tu&on	  of	  the	  aroma&c	  amine	  is	  faster	  than	  the	  displacement	  of	  the	  halogen.	  Minimum	  Structural	  Requirement	  •  The	  combina&on	  of	  a	  4-­‐chloro	  subs&tuent	  on	  the	  naphthalimide	  ring	  and	  an	  electron-­‐withdrawing	  subs&tuent	  on	  the	  N-­‐aryl	  ring	  is	  sufficient	  for	  heterocycle	  cleavage	  to	  be	  effected	  by	  primary	  amine	  nucleophiles	  Brønsted	  Plot	  •  Brønsted	  catalysis	  law:	  	  log10	  k	  =αlog10	  Ka	  +	  C	  – α=0:	  no	  acid	  catalysis	  – α=1:	  specific	  acid	  catalysis	  – 0<α<1:	  general	  acid	  catalysis	  •  The	  plot	  of	  log10	  k	  vs.	  against	  (-­‐pKa)	  for	  the	  alcohol	  is	  linear	  (slope=0.43,	  R2=0.99),	  a	  clear	  indicaGon	  of	  general	  acid	  catalysis	  during	  the	  acGvated	  step.	  Acknowledgments	  We	  are	  happy	  to	  acknowledge	  the	  financial	  support	  of:	  •  The	  Petroleum	  Research	  Fund,	  administered	  by	  the	  American	  Chemical	  Society	  •  University	  of	  Wisconsin-­‐Eau	  Claire	  Office	  of	  Research	  and	  Sponsored	  Programs	  Brønsted	  Plot	  Summary	  •  The	  -­‐pKa	  of	  the	  alcohols	  was	  ploJed	  versus	  the	  log	  k	  to	  explore	  the	  possibility	  of	  acid	  catalysis	  by	  the	  alcohols.	  •  The	  plot	  is	  linear	  (slope=0.43,	  R2=0.99),	  a	  clear	  indicaTon	  of	  general	  acid	  catalysis	  during	  the	  acTvated	  step.	  – A	  slope	  of	  1.0	  would	  indicate	  specific	  acid	  catalysis	  and	  0.0	  would	  indicate	  no	  acid	  catalysis.	  Effects	  of	  Solvent	  •  AJempts	  to	  explore	  effect	  of	  the	  concentraTon	  of	  the	  amine	  using	  alcohol	  cosolvents	  resulted	  in	  accelera*on	  of	  the	  displacement	  reacTon.	  •  We	  studied	  four	  alcohols	  to	  examine	  the	  solvent	  effects:	  –  methanol	  (pKa	  15.54)	  –  1-­‐propanol	  (pKa	  16.0)	  –  2-­‐propanol	  (pKa	  16.5)	  –  tert-­‐butyl	  alcohol	  (pKa	  17.0)	  •  The	  trend	  in	  reacTon	  rates	  appears	  to	  correlate	  with	  the	  alcohols’	  ability	  to	  act	  as	  a	  hydrogen	  bond	  donor.	  Is	  the	  Effect	  of	  the	  N-­‐Phenyl	  Ring	  Simply	  Steric?	  •  The	  N-­‐cyclohexyl	  analogue	  was	  prepared	  •  It	  was	  treated	  with	  butylamine.	  •  The	  displacement	  of	  the	  halogen	  was	  the	  only	  reacAon	  that	  occurred.	  •  Thus,	  the	  N-­‐aryl	  group	  is	  essenAal	  for	  subsAtuAon	  of	  the	  heterocyclic	  nitrogen.	  	  Replacement	  by	  a	  similar	  bulky	  alkyl	  group	  is	  not	  sufficient.	  	  	  What	  About	  the	  SubsAtuent	  at	  the	  4-­‐PosiAon?	  •  The	  reacAon	  of	  the	  4-­‐dimethylamino	  derivaAve	  at	  right	  with	  butylamine	  was	  extremely	  slow,	  and	  it	  gave	  only	  the	  product	  of	  displacement	  of	  the	  dimethylamino	  group.	  •  No	  displacement	  of	  the	  phenyl	  ring	  was	  observed	  •  An	  electron-­‐releasing	  group	  at	  the	  4-­‐	  posiAon	  bearing	  a	  lone	  pair	  and	  capable	  of	  conjugaAng	  with	  the	  imide	  carbonyl	  groups	  suppresses	  subsAtuAon	  of	  the	  heterocyclic	  nitrogen.	  	  

Kinetics of Competing Reactions of N-aryl-4-chloro-1,8-naphthalimides with Primary Amines

http://digital.library.wisc.edu/1793/62960

Kinetics of Competing Reactions of N-aryl-4-chloro-1,8-naphthalimides with Primary Amines

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