Nucleophilic Substitution of
Hydrogen in Nitroarenes: A New Chapter of Aromatic Chemistry

Mieczysław Mąkosza

doi:10.1055/s-0030-1260668

Subscribe to RSS

Please copy the URL and add it into your RSS Feed Reader.

https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000084.xml

Share / Bookmark

Facebook X Linkedin Weibo

Download PDF

Synthesis 2011(15): 2341-2356
DOI: 10.1055/s-0030-1260668

REVIEW

Nucleophilic Substitution of Hydrogen in Nitroarenes: A New Chapter of Aromatic Chemistry

Mieczysław Mąkosza*
Institute of Organic Chemistry PAS, Kasprzaka 44/52, 01-224 Warsaw, Poland
Fax: +48(22)6326681; e-Mail: icho-s@icho.edu.pl;

Further Information

Publication History

Received 11 February 2011
Publication Date:
15 June 2011 (online)

Abstract
Full Text
References

Permissions and Reprints All articles of this category

Abstract

Basic concepts, mechanistic principles and the broad application of nucleophilic substitution of hydrogen in nitroarenes and other electron-deficient arenes in organic synthesis are presented in a concise way. It was shown that the initial process between nucleophiles and (halo)nitroarenes is a fast and reversible addition - in positions occupied by hydrogen - to form anionic σ^H adducts that can then be converted into products of nucleophilic substitution of hydrogen in a few ways. Only when these pathways for rapid conversion of the σ^H adducts into products of nucleophilic substitution of hydrogen are not available, do the σ^H adducts dissociate. The subsequent slower formation of σ^X adducts, followed by departure of X anions, results in the conventional nucleophilic aromatic substitution of halogens, namely the S_NAr reaction. Thus the S_NAr reaction is a secondary ipso substitution, whereas nucleophilic substitution of hydrogen is a primary fast process. It is therefore necessary to introduce corrections in appropriate chapters of textbooks and monographs.

1 Introduction

2 Oxidative Nucleophilic Substitution of Hydrogen (ONSH)

3 Vicarious Nucleophilic Substitution of Hydrogen (VNS)

4 Other Ways of Converting the σ^H Adducts

5 Application of Nucleophilic Substitution of Hydrogen in Organic Synthesis

5.1 Introduction of Carbon Substituents

5.2 Introduction of Heteroatom Substituents

5.3 Construction of Carbo- and Heterocyclic Rings

6 Concluding Discussion

Key words

oxidative nucleophilic substitution - vicarious nucleophilic substitution - mechanism - electron-deficient arenes

References

1 Chupakhin ON. Charushin VN. van der Plas HC. Nucleophilic Aromatic Substitution of Hydrogen Academic Press; San Diego: 1994.

Google Scholar
2 Terrier F. Nucleophilic Aromatic Displacement Verlag Chemie; Weinheim: 1991.

Google Scholar
3a Mąkosza M. Winiarski J. Acc. Chem. Res. 1987, 20: 282

Google Scholar
3b Mąkosza M. Russ. Chem. Bull. 1996, 45: 491

Google Scholar
3c Mąkosza M. Kwast A. J. Phys. Org. Chem. 1998, 11: 341

Google Scholar
3d Mąkosza M. Wojciechowski K. Chem. Rev. 2004, 104: 2631

Google Scholar
4 Mąkosza M. Chem. Soc. Rev. 2010, 39: 2855

Crossref Google Scholar
5a Charushin VN. Chupakhin ON. Mendeleev Commun. 2007, 17: 243

Google Scholar
5b Chupakhin ON. Charushin VN. van der Plas HC. Tetrahedron 1988, 44: 1

Google Scholar
6a Clayden J. Greeves N. Warren S. Wothers P. Organic Chemistry Oxford University Press Inc.; New York: 2001.

Google Scholar
6b Anslyn EV. Daugherty WA. Modern Physical Organic Chemistry University Science Books; Sausalito: 2006.

Google Scholar
6c Moloney MG. Structure and Reactivity in Organic Chemistry Blackwell; Cambridge MA: 2008.

Google Scholar
7a Carey FA. Sundberg RJ. Advanced Organic Chemistry, Part A and B 5th ed.: Springer; Heidelberg: 2007.

Google Scholar
7b March J. Smith MB. March’s Advanced Organic Chemistry: Reactions, Mechanisms and Structure 6th ed.: J. Wiley; New York: 2007.

Google Scholar
8 Schlosser M. Ruzziconi R. Synthesis 2010, 2111

Article in Thieme Connect Google Scholar
9 Miller J. Aromatic Nucleophilic Substitution Elsevier; Amsterdam: 1968.

Google Scholar
10a von Richter V. Chem. Ber. 1871, 4: 21

Google Scholar
10b Rosenblum MJ. J. Am. Chem. Soc. 1960, 82: 3796

Google Scholar
11 Davis RB. Pizzini LC. J. Org. Chem. 1960, 25: 1884

Crossref Google Scholar
12 Mąkosza M. Paszewski M. Pol. J. Chem. 2005, 79: 163

Google Scholar
13a Hamana M. Iwasaki G. Saeki S. Heterocycles 1982, 17: 177

Google Scholar
13b Mąkosza M. Sypniewski M. Tetrahedron 1994, 50: 4913

Google Scholar
14a Mąkosza M. Staliński K. Chem. Eur. J. 1997, 3: 2025

Google Scholar
14b Mąkosza M. Staliński K. Tetrahedron Lett. 1998, 39: 3575

Google Scholar
15 Kienzle K. Helv. Chim. Acta 1978, 61: 449

Crossref Google Scholar
16 Kraus GA. Selvakumar N. J. Org. Chem. 1998, 63: 9846

Crossref Google Scholar
17 Mąkosza M. Surowiec M. Szczepańska A. Sulikowski D. Maltsev O. Synlett 2007, 470

Google Scholar
18a Adam W. Mąkosza M. Staliński K. Zhao CG. J. Org. Chem. 1998, 63: 4390

Google Scholar
18b Adam W. Mąkosza M. Zhao C.-G. Surowiec M. J. Org. Chem. 2000, 65: 1099

Google Scholar
19a Gallardo I. Guirado G. Marquet J. Chem. Eur. J. 2001, 7: 1759

Google Scholar
19b Goumont R. Jan E. Mąkosza M. Terrier F. Org. Biomol. Chem. 2003, 1: 2192

Google Scholar
20 Malykhin EV. Kolesnichenko GA. Shteingarts VD. Zh. Org. Khim. 1985, 21: 1150

Google Scholar
21a van der Plas HC. Wożniak M. Croat. Chem. Acta 1986, 59: 33

Google Scholar
21b Wożniak M. Barański A. Szpakiewicz B. Liebigs Ann. Chem. 1991, 875

Google Scholar
21c Szpakiewicz B. Grzegorzek M. Zh. Org. Khim. 2004, 40: 869

Google Scholar
22a Bartoli G. Acc. Chem. Res. 1984, 17: 109

Google Scholar
22b Mąkosza M. Surowiec M. J. Organomet. Chem. 2001, 624: 167

Google Scholar
23a Mąkosza M. Sulikowski D. J. Org. Chem. 2009, 74: 3827

Google Scholar
23b Mąkosza M. Kamieńska-Trela K. Paszewski M. Bechcicka M. Tetrahedron 2005, 61: 11952

Google Scholar
23c Sanchez CM. Iglesias J. Lopez JG. Alvarez IJP. Ortiz FL. Tetrahedron 2006, 62: 3642

Google Scholar
24a Goliński J. Mąkosza M. Tetrahedron Lett. 1978, 19: 3495

Google Scholar
24b Mąkosza M. Glinka T. J. Org. Chem. 1983, 48: 3860

Google Scholar
25 Mąkosza M. Stalewski J. Liebigs Ann. Chem. 1991, 605

Google Scholar
26a Mąkosza M. Ludwiczak S. J. Org. Chem. 1984, 49: 4562

Google Scholar
26b Mąkosza M. Mathur SN. Biaecki M. Pol. J. Chem. 1998, 72: 1198

Google Scholar
27a Mąkosza M. Chylińska B. Mudryk B. Liebigs Ann. Chem. 1984, 8

Google Scholar
27b Kwast E. Mąkosza M. Tetrahedron Lett. 1990, 31: 121

Google Scholar
27c Jończyk A. Kowalkowska A. Synthesis 2002, 674

Google Scholar
28a Mąkosza M. Goliński J. Rykowski A. Tetrahedron Lett. 1983, 24: 3277

Google Scholar
28b Katrusiak A. Tetrahedron Lett. 2006, 47: 4259

Google Scholar
29 Mąkosza M. Kuciak R. Wojciechowski K. Liebigs Ann. Chem. 1994, 615

Google Scholar
30 Neidlein R. Lautenschlager G. Chem. Ber. 1989, 122: 493

Crossref PubMed Google Scholar
31 Mąkosza M. Rydz A. Wróbel Z. Pol. J. Chem. 1995, 69: 918

Google Scholar
32a Mąkosza M. Sienkiewicz K. J. Org. Chem. 1998, 63: 4199

Google Scholar
32b Pews RG. Lysenko Z. Vosejpka PC. J. Org. Chem. 1997, 62: 8255

Google Scholar
33a Angeli A. Angelico F. Gazz. Chim. Ital. 1901, 31: 27

Google Scholar
33b Price CC. Voong S.-T. Org. Synth. 1955, 28: 86

Google Scholar
34a Katritzky AR. Laurenzo KS. J. Org. Chem. 1986, 51: 5039

Google Scholar
34b Pagoria PF. Mitchell ARR. Schmidt D. J. Org. Chem. 1996, 61: 2934

Google Scholar
35a Mąkosza M. Biaecki M. J. Org. Chem. 1998, 63: 4878

Google Scholar
35b Seko S. Miyake K. J. Chem. Soc., Chem. Commun. 1998, 1519

Google Scholar
36a Bartoli G. Bosco M. Melandri A. Boicelli AC. J. Org. Chem. 1979, 44: 2087

Google Scholar
36b Wróbel Z. Kwast A. Synlett 2007, 1525

Google Scholar
37 Suwiński J. Œwierczek K. Tetrahedron 2001, 57: 1639

Crossref Google Scholar
38 Bażej S. Kwast A. Mąkosza M. Tetrahedron Lett. 2004, 45: 5413

Google Scholar
39 Mąkosza M. Varvounis G. Surowiec M. Giannopoulos T. Eur. J. Org. Chem. 2003, 3791

Google Scholar
40 van der Plas HC. Acc. Chem. Res. 1978, 11: 462

Crossref Google Scholar
41 Wróbel Z. Mąkosza M. Org. Prep. Proced. Int. 1990, 575

Google Scholar
42a Achmatowicz M. Thiel OR. Gorins G. Goldstein C. Affouard C. Jensen R. Larsen RD. J. Org. Chem. 2008, 73: 6793

Google Scholar
42b Bull DJ. Fry J. Mackenny MC. Malloy KA. Synlett 1996, 647

Google Scholar
43 Chhaly L. Pritzkow W. J. Prakt. Chem. 1994, 336: 558

Crossref PubMed Google Scholar
44a Mąkosza M. Surowiec M. Voskresensky S. Synthesis 2000, 1237

Google Scholar
44b Katritzky AR. Toader DJ. J. Org. Chem. 1997, 62: 4137

Google Scholar
45a Mąkosza M. Biaecki M. Synlett 1991, 181

Google Scholar
45b Tercel M. Lee AE. Hogg A. Anderson RF. Lee HH. Siim BG. Denny WA. Wilson WR. J. Med. Chem. 2001, 44: 3511

Google Scholar
46 Mąkosza M. Winiarski J. J. Org. Chem. 1984, 49: 5272

Crossref Google Scholar
47a Mąkosza M. Owczarczyk Z. J. Org. Chem. 1989, 54: 5094

Google Scholar
47b Crozet MD. Suspene C. Kaafarani M. Crozet MP. Vanelle P. Heterocycles 2004, 63: 1629

Google Scholar
48 Mąkosza M. Winiarski J. Chem. Lett. 1984, 1623

Google Scholar
49 Surowiec M. Mąkosza M. Tetrahedron 2004, 60: 5019

Crossref Google Scholar
50a Loska R. Majcher M. Mąkosza M. J. Org. Chem. 2007, 72: 5574

Google Scholar
50b Loska R. Mąkosza M. J. Org. Chem. 2007, 72: 1354

Google Scholar
51a Mąkosza M. Winiarski J. J. Org. Chem. 1980, 45: 1535

Google Scholar
51b Mąkosza M. Winiarski J. J. Org. Chem. 1984, 49: 1494

Google Scholar
51c Mąkosza M. Danikiewicz W. Wojciechowski K. Liebigs Ann. Chem. 1988, 203

Google Scholar
52 Stahly GP. Stahly BC. Lilje KC. J. Org. Chem. 1984, 49: 578

Crossref Google Scholar
53a Mąkosza M. Goliński J. Baran J. J. Org. Chem. 1984, 49: 1488

Google Scholar
53b Mąkosza M. Glinka T. Kinowski J. Tetrahedron 1984, 40: 1863

Google Scholar
54a Mąkosza M. Goliński J. Angew. Chem., Int. Ed. Engl. 1982, 21: 488

Google Scholar
54b Lawrence NJ. Liddle J. Jackson D. Tetrahedron Lett. 1995, 36: 8477

Google Scholar
55 Mąkosza M. Kinowski A. Ostrowski S. Synthesis 1993, 1215

Article in Thieme Connect Google Scholar
56a Lawrence NJ. Liddle J. Jackson DA. Synlett 1996, 55

Google Scholar
56b Florio S. Lorusso P. Granito C. Luisi R. Troisi L. J. Org. Chem. 2004, 69: 4961

Google Scholar
57b Sulikowski D. Mąkosza M. Eur. J. Org. Chem. 2010, 4218

Google Scholar
58 Mąkosza M. Sulikowski D. Maltsev O. Synlett 2008, 1711

Article in Thieme Connect Google Scholar
59 Mąkosza M. Sulikowski D. Synlett 2010, 1661

Article in Thieme Connect Google Scholar
60 Mąkosza M. Podraza R. Eur. J. Org. Chem. 2000, 193

Google Scholar
61 Bakke JM. J. Heterocycl. Chem. 2005, 42: 463

Crossref Google Scholar
62 Patriciu O.-I. Pillard C. Finaru A.-L. Sandulescu I. Guillaumet G. Synthesis 2007, 3868

Article in Thieme Connect Google Scholar
63 Stern KM. Hileman FD. Bashkin JK. J. Am. Chem. Soc. 1992, 114: 9237

Crossref Google Scholar
64 Mitchell AR. Coburn MD. Schmidt RD. Pagoria PF. Lee GS. Termochim. Acta 2002, 384: 205

Crossref Google Scholar
65 Mąkosza M. Paszewski M. Sulikowski D. Synlett 2008, 2938

Article in Thieme Connect Google Scholar
66a Tyraa A. Mąkosza M. Synthesis 1994, 264

Google Scholar
66b Mąkosza M. Krylova I. Eur. J. Org. Chem. 1998, 2229

Google Scholar
68 Moskalev N. Barbasiewicz M. Mąkosza M. Tetrahedron 2004, 60: 347

Crossref Google Scholar
69 Moskalev N. Mąkosza M. Heterocycles 2000, 52: 533

Crossref Google Scholar
70a Mąkosza M. Hoser H. Heterocycles 1994, 37: 1701

Google Scholar
70b Mąkosza M. Paszewski M. Synthesis 2002, 2203

Google Scholar
71 Wojciechowski K. Mąkosza M. Tetrahedron Lett. 1984, 25: 4793

Crossref Google Scholar
72a Wojciechowski K. Mąkosza M. Synthesis 1992, 571

Google Scholar
72b Wojciechowski K. Synth. Commun. 1997, 27: 135

Google Scholar
73a Wróbel Z. Mąkosza M. Synlett 1993, 597

Google Scholar
73b Mąkosza M. Wróbel Z. Tetrahedron 1997, 53: 5501

Google Scholar
74a Lerman L. Weinstock-Rosin M. Nudelman A. Synthesis 2004, 3043

Google Scholar
74b Jeanty M. Surenet F. Guillaumet G. J. Org. Chem. 2008, 73: 7310

Google Scholar
75 Andreassen EJ. Bakke JM. Sletvold I. Svensen H. Org. Biomol. Chem. 2004, 2: 2671

Crossref Google Scholar
76a Wojciechowski K. Mąkosza M. Bull. Soc. Chim. Belg. 1986, 95: 671

Google Scholar
76b Wojciechowski K. Mąkosza M. Synthesis 1986, 651

Google Scholar
77 Mąkosza M. Tyraa A. Acta Chem. Scand. 1992, 46: 689

Crossref Google Scholar
78 Wróbel Z. Kwast A. Mąkosza M. Synthesis 1993, 31

Article in Thieme Connect Google Scholar
79 Mąkosza M. Niyazimbetov M. Synlett 1992, 417

Article in Thieme Connect Google Scholar
80 Danikiewicz W. Mąkosza M. J. Org. Chem. 1991, 56: 1283

Crossref Google Scholar
81 Wróbel Z. Eur. J. Org. Chem. 2000, 521

Google Scholar
82a Bobin M. Kwast A. Wróbel Z. Tetrahedron 2007, 63: 11048

Google Scholar
82b Bujok R. Kwast A. Cmoch P. Wróbel Z. Tetrahedron 2010, 66: 698

Google Scholar
82c Wróbel Z. Wojciechowski K. Kwast A. Gajda N. Synlett 2010, 2435

Google Scholar
83a Mayr H. Patz M. Angew. Chem., Int. Ed. Engl. 1994, 33: 938

Google Scholar
83b Mayr H. Ofial AR. Pure Appl. Chem. 2005, 77: 1808

Google Scholar
84a Mąkosza M. Bażej S. Chem. Eur. J. 2008, 14: 11113

Google Scholar
84b Seelinger F. Bażej S. Bernhardt S. Mąkosza M. Mayr H. Chem. Eur. J. 2008, 14: 6108

Google Scholar

67

Mąkosza, M.; Wojciechowski, K. In Targets in Heterocyclic Systems, Vol. 14; Attanasi, O.A.; Spinelli, D. Eds.; Società Chimica Italiana: Roma, 2010.