GET THE APP

Eco-friendly Synthesis of α -Aminonitriles Catalysed by Epzg

Der Pharma Chemica
Journal for Medicinal Chemistry, Pharmaceutical Chemistry, Pharmaceutical Sciences and Computational Chemistry

ISSN: 0975-413X

ilbet

süperbetin giriş

All submissions of the EM system will be redirected to Online Manuscript Submission System. Authors are requested to submit articles directly to Online Manuscript Submission Systemof respective journal.

agariookey oyna istanbul okey

Research Article - Der Pharma Chemica ( 2022) Volume 14, Issue 6

Eco-friendly Synthesis of α -Aminonitriles Catalysed by Epzg

Rahul Patil1*, Ankush Mali1, Shivaji Burungale1, Uday Lad1, Sanjay Jadhav1 and Uttam More2
 
1Department of Chemistry, Yashwantrao Chavan College of Science, Karad-415 124, India
2Department of Chemistry, S. G. M. College, Karad-415 124, India
 
*Corresponding Author:
Rahul Patil, Department of Chemistry, Yashwantrao Chavan College of Science, Karad-415 124, India, Email: [email protected]

Received: 06-Jun-2022, Manuscript No. dpc-22-65962; Editor assigned: 08-Jun-2022, Pre QC No. dpc-22-65962; Reviewed: 22-Jun-2022, QC No. dpc-22-65962; Revised: 23-Jun-2022, Manuscript No. dpc-22-65962; Published: 30-Jun-2022, DOI: 10.4172/0975-413X.14.6.31-37

Abstract

A simple, proficient and ecofriendly procedure has been developed for the three component coupling of aromatic aldehyde, substituted amines and trimethylsilyl cyanide produce α-amino nitriles. The α-amino nitriles are synthesized in high yields (90-91%) in a few minutes (18-45 min) under solvent-free conditions using EPZG catalyst at room temperature.

Keywords

α-amino nitriles; EPZG; Ecofriendly; Room temperature

INTRODUCTION

Nitriles are the building blocks of most biologically active substances and natural products. However, amides and carboxylic acids [1-2] have synthesized from nitriles, due to this α-aminonitriles have occupied great position in synthetic organic chemistry, this growing demand of nitriles, satisfied by Strecker reaction [3]. Strecker in 1850 reported the synthesis of α-aminonitriles by multicomponent condensation of aldehyde, amine and hydrogen cyanide [3] hydrocyanation of emines is thus basic C-C bond formation reaction [4] involves conversion of nitriles to carbonyl group [5-6]. Modified Strecker reaction i.e. synthesis of optically active α-amino acid by the hydration of cyanide [7], α-aminonitriles is acts a precursor fragment for the synthesis of α-amino acid [8], imidazole and several biologically active compounds [9] containing nitrogen atom. Bifunctionality of α-aminonitriles acts as a building blocks of pharmaceutical industries [11], such as serine protease inhibitors [12], (-, +)phtalascidine 650 [13] and also in the synthesis of boron containing retinoids [14]. Synthesis of heterocyclic moiety such as 1,2,3-diazaphospholidines, imidazole, oxazoles, and isothiozoles [15] derived from 2-amino-2-alkyl(aryl) propanenitriles as a starting material. Synthesis of 5-amino-4H-imidazoles was achieved by reacting α-aminonitriles with imidoester which is a key material of many biological compounds. Different ptotocols have been eported for the synthesis of α–aminonitriles such as Formic acid [16], ammonium chloride [17], PPh3/DEAD[18], Bicyclic Guanidine [19], polyethylene glycol (PEG-OSO3H) [20], MgI2 [21], sulphated polyborate [22], PEG -400 [23], Zn(CN) [24], cinchona-based thiourea alkaloid [25], 5mol % to 20mol % L –prolineamide derived N,N’-dioxide [26], Ga(OTF)3[27], Nafion –H and NafionSAC-13 [28], SBA-15 supported sulphonic acid [29], indium (III) iodide [30], mesoporous MCM-41 catalyst [31], ionic liquid [bmim]BF4 or MgBr2.OEt2 [32], Bismuth Nitrate [33], Fe3O4@SiO2@Me&Et-PhSO3H [34], Task- Specific ionic liquid [35], chiral ammonium trifluoroacetate, potassium hexacyanoferrate (II) [36], Silica based Scandium (III) [37], Pd(II) [38], magnetically separable nanoparticles [39,40]. We have reported here environmentally green EPZG as catalyst for the synthesis of α–aminonitriles. EPZG is a FeCl3 supported on clay.

Present work

It was clear from the literature review that α–aminonitriles has greater utility in medicinal chemistry as well as in agricultural fields. we have report herein Lewis acid EPZGR [41-51] catalyzed solvent free synthesis of α–aminonitriles at room temperature (Scheme 1) (Table 1-4).

Table 1: Screen of catalyst for the synthesis of α –aminonitrile

Sr. No catalyst Amount Time in minute Yield
mg %
>1 EPZGR 10 40 60
2 EPZGR 15 34 88
3 EPZGR 20 30 91
4 EPZGR 25 30 91
5 EPZGR 30 30 91
Reaction condition: Benzaldehyde (1mmol); aniline (1mmol); trimethylsilyl cyanide (1mmol); EPZGR catalyst 20mg; at room temperature.

Table 2: Screening of solvents for the synthesis of α –aminonitrile

Entry Solvent Time (Min.) Yield%
>1 Water 60 69
2 Alcohol 52 58
3 Solvent free 30 91
4 Chloroform 64 69
5 Dichloromethane 70 54
6 Dimethylsulphoxide 90 53
Reaction condition: -Benzaldehyde (1mmol); aniline (1mmol); trimethylsilyl cyanide(1mmol); EPZGR catalyst 20mg; at room temperature.

Table 3: Reusability of catalyst for the synthesis of α –aminonitrile

Sr. No. Catalyst Amount mg Time in minute Yield%
>1 EPZGR 20 30 91
2 EPZGR 20 30 91
3 EPZGR 20 31 90
4 EPZGR 20 32 89
5 EPZGR 20 32 88
Reaction condition: Benzaldehyde (1mmol); aniline (1mmol); trimethylsilyl cyanide (1mmol); EPZGR catalyst 20mg; at room temperature.

Table 4: Multicomponent synthesis of α-aminonitriles

  Entry   Aldehyde Amine Product   Time min.   Yield %
> a

image

image image 30 94
  b  image  image image   30   91
c image image image 18 93
d image image image 29 91
e image image image 21 93
f image image image 45 87
g image image image 22 89
h image image image 27 90
i image image image 20 92
j image image image 42 83
k image image image 25 87
l image image image 27 90
m image image image 32 91
n image image image 31 89
o  image image image 30 88
Reaction condition: Benzaldehyde (1mmol); aniline (1mmol); trimethylsilyl cyanide (1mmol); EPZGR catalyst 20mg; at room temperature.
derpharmachemica-Multicomponent

Scheme 1: Multicomponent synthesis of α –aminonitriles

EXPERIMENTAL SECTION

General

Various substituted aldehyde (Sigma-Aldrich), aniline (Himedia), Trimethylsilyl cyanide (Himedia) were used as received without purification. Melting point measures by melting point apparatus made by Equiptronics model No – EQ- 730A. IR spectra were recorded on FT-IR -7600 Lambda Scientific Spectrometer. NMR Spectra were recorded on a Bruker AC400 MHz spectrometer in CDCl3 using tetramethyl silane as an internal standard material.

General Experimental Procedure

In a 25ml round bottom flask mixture of aldehyde (1mmol), aniline (1mmol) and Trimethylsilyl cyanide (1mmol) was stirred with EPZGR catalyst 20 mg at room temperature for desired time mentioned in Table 2; Entry b completion of reaction was monitored by TLC. Upon completion of reaction crystallization of the product was carried out in ethanol. All the products were purified by same technique and found to be correct. Further structures of the product were confirmed by 1H NMR, 13C NMR, HRMS and IR.

CONCLUSION

We have developed simple process of synthesis of α-aminonitriles by reacting aldehyde, amine and Trimethylsilyl cyanide. New process which was easily applicable, easy separation of product and catalyst, short reaction time at room temperature. Recyclability of the catalyst was found to be efficient for successive five times without loss of its activity.

Spectral data of synthesized α-aminonitriles.

Table 3, Entry a : 2-(4-methoxyphenyl)-2-(phenylamino)acetonitrile, Color: White; M. P.: 94-96ºC; IR (KBr): 3386, 3029, 2249, 1892, 1594, 1498, 1428, 1262, 1192, 1105, 834, 746, 675cm-1;1H NMR (400MHz, CDCl3):δ (ppm):3.86(s, 3H, -OCH3), 4.00-4.02(d, 1H, -NH,J = 8Hz), 5.38- 5.40(d, 1H, -CH, J = 8Hz), 6.78-7.54(m, Ar-H);13C NMR (100 MHz, CDCl3 ): δ (ppm):49.68, 55.45,114.10, 114.65, 118.44, 120.20,125.95, 128.65, 129.58,114.75, 160.45; HRMS:238.16;Calculated mass: 238.28.

Table 3, Entry b : 2-(phenyl)-2-(phenylamino)acetonitrile, Color: White; M. P.: 80-82ºC; IR (KBr):3317, 3036, 2242, 1918, 1994, 1489, 1393, 1271, 1096, 999, 746cm-1;1H NMR(400MHz, CDCl3):δ (ppm): 4.04-4.06 (d, 1H, -NH, J = 8Hz),5.44-5.46 (d, 1H, -CH, J = 8Hz),6.78-7.63 (m, Ar- H); 13C NMR (100 MHz, CDCl3):δ (ppm): 50.19,114.12,118.21, 120.29, 127.29, 129.37, 129.58, 129.60, 133.89, 144.65;

Table 3, Entry d : 2-(4-isopropylphenyl)-2-(phenylamino)acetonitrile, Color:White, M. P.:78-80 ºC.IR (KBr): 3395, 2949, 2897, 2242, 1918, 1603, 1515, 1441, 1296, 1105, 912, 825, 746, 684cm-1;1H NMR(400MHz, CDCl3):δ (ppm): 1.27-1.29 (d, 6H, -CH3, J = 8Hz), 2.93-3.00 (m, 1H, - CH, J = 8Hz),4.00-4.02 (d, 1H, -NH, J = 8Hz), 5.39-5.41 (d, 1H, -CH, J = 8Hz),6.78-7.54 (m, Ar-H); 13C NMR (100 MHz, CDCl3 ): δ (ppm): 23.91, 33.92, 49.94, 114.01, 118.37, 120.16, 127.34,127.43,129.58,131.25,144.75,150.57;

Table 3, Entry f : 2-(2-chlorophenyl)-2-(phenylamino)acetonitrile, Color: White; M. P.: 62-64ºC;IR (KBr):3335, 3020, 2249, 1927, 1594, 1498, 1296, 1236, 1061, 947, 755, 675cm-1; 1H NMR(400MHz, CDCl3): δ (ppm): 4.03-4.0 (d, 1H, -NH, J = 8Hz), 5.73-5.75 (d, 1H, -CH, J = 8Hz), 6.79-7.77 (m, Ar-H);13C NMR (100 MHz, CDCl3):δ (ppm):48.03, 114.24,117.76,120.48,127.82,129.07, 29.60,130.49,131.07,131.7, 133.55,142.52;

Table 3, Entry h : 2-(3-nitrophenyl)-2-(phenylamino)acetonitrile, Color: Yellow; M. P.: 86-88ºC; IR (KBr):3323, 3107, 3062, 2243, 1920, 1613, 1541, 1543, 1226, 1082, 893, 758, 975cm-1; 1H NMR (400MHz, CDCl3):δ (ppm): 4.20-4.22 (d, 1H, -NH, J = 8Hz), 5.58-5.60 (d, 1H, -CH, J = 8Hz), 6.78-8.51 (m, Ar-H);13C NMR (100 MHz, CDCl3 ): δ(ppm): 49.62, 114.58, 117.19,121.09,122.38, 124.53, 129.72,130.50,133.05, 136.09, 143.89, 148.75;

Table 3,Entry j : 2-(3-hydroxyphenyl)-2-(phenylamino)acetonitrile, Color : White; M.P.:86-88ºC IR (KBr): 3402, 3072, 2249, 2010, 1615, 1504, 1348, 1275, 1063, 854, 794, 676cm-1; 1H NMR (400MHz, CDCl3): δ (ppm): 3.98-4.00 (d, 1H, -NH, J = 8Hz), 5.43-5.45 (d, 1H, -CH, J = 8Hz), 6.66-7.74 (m, Ar-H), 9.38 (bs, HO-Ar); 13C NMR (100 MHz, CDCl3): δ(ppm): 49.20,113.96,114.31, 116.30, 117.95, 118.88, 129.08, 129.22, 130.10, 131.08, 132.04, 132.06, 132.09, 133.11, 133.17, 145.77, 158.03; 130.23, 133.34, 133.50, 133.86, 133.94, 133.99, 135.52, 136.99, 150.55, 152.38, 162.95, 165.38, 168.45;

Table 3, Entry l : 2-(phenyl)-2-(4-chlorophenylamino)acetonitrile, Color: White; M. P.:80-82 ºC;IR (KBr): 3317, 3045, 2242, 1603, 1489, 1262, 1069, 834, 693 cm-1; 1H NMR( 400MHz, CDCl3): δ (ppm): 4.09-4.11(d, 1H, -NH, J = Hz), 5.38-5.40(d, 1H, -CH, J = 8Hz), 6.69-7.60 (m, Ar-H); 13C NMR (100 MHz, CDCl3 ): δ(ppm):50.28, 115.38, 117.89, 122.22, 125.14, 127.23, 128.85,128.89,129.25,129.43, 129.48, 129.71,133.48,143.20,160.80;

Table 3, Entry n : 2-(4-isopropylphenyl)-2-(4-methoxyphenylamino)acetonitrile, Color: White;M. P.:78-80 ºC;IR (KBr): 3395, 2958, 2224, 1603, 1498, 1236, 1025, 834, 755, 650cm-1;1H NMR( 400MHz, CDCl3):δ (ppm): 1.27-1.29 (d, 6H, 2CH3 ofisopropyl gr.J = 8Hz), 2.93-3.00(m, 1H, -CH of isopropyl gr. J = 8Hz), 3.78 (s, OCH3),5.31-5.33(d, 1H, -CH, J8Hz),6.76-7.54(m, Ar-H); 13C NMR (100 MHz, CDCl3): δ (ppm): 24.02, 34.15,51.28,55.66,114.99,116.14,118.64,127.30,127.34, δ = 131.51,138.43, 154.02;

Table 3, Entry o : 2-(4-methoxyphenyl)-2-(4-methoxyphenylamino)acetonitrile, Color: White; M. P.:134-134 ºC; IR (KBr): 3530, 2942, 2248, 1630, 1460, 1251, 989, 874, 649cm-1; 1H NMR( 400MHz, CDCl3):δ (ppm): 3.49 (s, -OCH3),4.04 (s, -OCH3),5.30-5.32 (d, 1H, -CH, J = 8Hz),6.29-8.14 (m, Ar-H);13C NMR (100 MHz, CDCl3): δ (ppm): 54.17,55.12, 115.22, 117.33, 119.43, 126.19, 127.56,130.49,139.12,156.62;

Table 3, Entry p : 2-(phenyl)-2-(4-nitrophenylamino)acetonitrile, Color: White; M. P.:94-96 ºC ;IR (KBr): 3381,2949, 2246, 1612, 1479, 1269, 1015,843, 664cm-1; 1H NMR( 400MHz, CDCl3) :δ (ppm): 4.96-4.98 (d, 1H, -CH, J = 8Hz),5.56-5.58(d, 1H, -CH, J = 8Hz),6.60-8.43 (m, Ar-H);13C NMR (100 MHz, CDCl3): δ (ppm): 49.14, 114.52, 118.11, 123.02, 124.11, 128.05,128.95,130.14,131.44,132.64, 145.59, 161.12;

Table 3, Entry q : 2-(2-chlorophenyl)-2-(4-nitrophenylamino)acetonitrile, Color: White; M. P.:104-106 ºC ; IR (KBr): 3340, 3012, 2246, 1970, 1592, 1498, 1293, 1242, 1063, 945, 789, 674 cm-1; 1H NMR( 400MHz, CDCl3): δ (ppm): 4.40-4.42 (d, 1H, -CH, J = 8Hz),5.80-5.82 (d, 1H, -CH, J = 8Hz),6.60-8.30 (m, Ar-H); 13C NMR (100 MHz, CDCl3): δ (ppm): 48.72, 115.88, 117.72, 124.19, 129.55, 129.91, 129.98,130.12,130.33,131.27, 132.46, 158.17;

REFERENCES

  1. Rappoport Z, John Wiley & Sons Ltd, New York, NY, USA, 1970, 52: p. 1737-1746.
  2. Zhang G, Zheng D, NieJ Wang T, et al., Org Biomol Chem. 2010, 8: p. 1399-1405.
  3. Strecker A. Liebigs Ann Chem. 1850, 75: p. 27-45.
  4. Google Scholar, Crossref

  5. Yet L. Angew Chem Int Ed. 2001, 40: p. 875-877.
  6. Google Scholar, Crossref

  7. Enders D, Kirchhoff J, Gerdes P, et al.,  Eur J Org Chem. 1998, 1: p. 63-72.
  8. Google Scholar, Crossref

  9. Danielson M, Falke J. Annu Rev Biophys Biomol Struct. 1996, 25: p. 163-195, 1996.
  10. Indexed at, Google Scholar, Crossref

  11. Shafran Y, Bakulev V, Mokrushin V. Russ Chem Rev. 1989, 58: p. 148-162..
  12. Matier W, Owens D, Comer W, et al., J Med Chem. 1973, 16: p. 901-908.
  13. Google Scholar, Crossref

  14. Martinez, Corey E. Org Lett. 1999, 1: p. 75-78.
  15. Indexed at, Google Scholar, Crossref

  16. Enders D, Shilvock J. Chem Soc Rev. 2000, 29: p. 359-373.
  17. Google Scholar   

  18. ArasappanA, VenkatramanS, Padilla A, et al., Tetrahedron Lett. 2007, 48: p. 6343.
  19. Indexed at, Google Scholar, Crossref

  20. Razafindrabe C, Aubry S, Bourdon B, et al., Tetrahedron. 2010, 66: p. 9061-9066.
  21. Google Scholar, Crossref

  22. Das B, Anguiano J, Mahalingam S. Tetrahedron Lett. 2009, 50: p. 5670-5672.
  23. Indexed at, Google Scholar, Crossref

  24. Drabina P, Sedlak M. Arkivoc. 2012, p.152.
  25. Avendano C, Ramos T, Gomez-Molinero E. J Heterocycl Chem. 1985, 22: p. 537.
  26. Google Scholar, Crossref

  27. Roshani M., Ghafuri H. RSC Adv. 2013, p. 1-3.
  28. Nammalwar B, Fortenberry C, Bunce R. Tetrahedron Lett. 2014, 55: p. 379-381.
  29. Google Scholar, Crossref

  30. Chaturvedi D, Chaturvedi A, Mishra N, et al., Tetrahedron Lett. 2012, 55: p. 5398-5401.
  31. Google Scholar, Crossref

  32. Li J, Jing W, Han K, et al., J Org Chem. 2003, 68: p. 8786-8789.
  33. Google Scholar, Crossref

  34. Shekouhy M. Catal Sci Technol. 2012, 2: p. 1010-1020.
  35. Google Scholar, Crossref

  36. Li P, Zhang Y, Chen Z, et al., Tetrahedron Lett. 2017, 58: p.1854-1858.
  37. Google Scholar    Crossref

  38. Indalkar K, Khatri C, Chaturbhuj G. Tetrahedron Lett. 2017, 58: p. 2144-2148.
  39. Google Scholar, Crossref

  40. Hu X, Ma Y, Li Z. J Organomet Chem. 2012, 705: p. 70-74.
  41. Indexed at, Google Scholar, Crossref

  42. Shah S, Singh B. Tetrahedron Lett. 2012, 53: p. 151-156.
  43. Google Scholar, Crossref

  44. Dong Y, Tian. Chem Commun. 2012, 48: p. 4899-4901.
  45. Huang J, Liu X, Wen Y, et al., J Org Chem. 2007, 72: p. 204-208.
  46. Google Scholar   

  47. Prakash G, Mathew T, Panja C, et al., Proc Natl Acad Sci. 2007, 104: p. 3703-3706.
  48. Indexed at, Google Scholar, Crossref

  49. Prakash G, Elizabeth T, Bychinskaya T, et al., Green chem. 2008, 10: p. 1105-1110.
  50. Google Scholar   

  51. Karimi B, Zareyee D. J Mater Chem. 2009, 19: p. 8665-8670.
  52. Google Scholar   

  53. Shen Z, Jun S, Loh T. Tetrahedron. 2008, 64: p. 8159-8163.
  54. Google Scholar, Crossref

  55. Maleki. Green Chem Lett Rev. 2018, 11: p. 36-46.
  56. Google Scholar, Crossref

  57. Safa K, Zeinolabedini A, Abbasi H, et al., J Iran Chem Soc. 2013, 10: p. 447-452.
  58. Indexed at, Google Scholar, Crossref

  59. Mansoor S, AswinK, Logaiya K. et al., J Saudi Chem Soc. 2016, 20: p. 138-150.
  60. Mobaraki A, Movassagh B, Karimi B. ACS Comb Sci. 2014, 16: p. 352-358.
  61. Indexed at, Google Scholar, Crossref

  62. Huang J, Corey E. Org Lett. 2004, 6: p. 5027-5029.
  63. Google Scholar, Crossref

  64. Zheng Li, Yuanhong Ma, Jun Xu, et al., Tetrahedron Lett. 2010, 51: p. 2022-2026.
  65. Karimi B, Safari A. J Organmet Chem. 2008, 693: p. 2967-2970.
  66. Jarusiewicz J, Choe Y, Yoo K. et al., J Org Chem. 2009, 7: p. 74.
  67. Google Scholar, Crossref

  68. Baghery S, Zolfigol M, Schirhagel R, et al., Nag N Appl Organometal Chem. 2017.
  69. Rakhtshah J. Sadegh Salehzadeh Res. chem. Intermed. 2017.
  70. Envirocats-Supported Reagents: Product information, Contract Chemicals, UK, 1994.
  71. Ponde D, Borate H, SudlaiA, et al., Tetrahedron Lett.1996, 37: p. 4605.
  72. Google Scholar    Crossref

  73. Bandgar BP, Kasture SP, Tidake  K, et al.,  Green Chem. 2000, 2, 152.
  74. Upadhya T, Daniel T, Sudlai A, et al., Synth Commun. 1996, 26: p. 4539.
  75. Google Scholar, Crossref

  76. Sonali Ghandande and Supriya Mahajan. Indian J Chem. 2005, p. 188-192.
  77. Bandgar BP, Uppalla LS and Sadavarte VS. Green Chemistry. 2001, 3: p. 39-41.
  78. Bandgar BP, Zirange MB, Wadgaonkar PP. Synlett. 1996, 2: p. 149.
  79. Indexed at, Google Scholar, Crossref

  80. Bandgar BP, Wadgaonkar PP. Synthetic Communication. 1997, 27: p. 2069.
  81. Google Scholar   

  82. Bandgar BP, Hazare CT, Wadgaonkar PP. J Chem Res(S). 1995, 1: p. 90.
  83. Bandgar BP, Jagtap SR, Ghodeshwar SB, et al., Synthetic Communication. 1995, 25: p. 2993.
  84. Google Scholar, Crossref

  85. Rahul Patil, Uday Lad, Suresh Shendage, et al., Rasayan J Chem. 2020, 13: p. 1735-1743.
  86. Google Scholar, Crossref

Select your language of interest to view the total content in your interested language

30+ Million Readerbase
SCImago Journal & Country Rank
Recommended Conferences
Google Scholar citation report
Citations : 11575

Der Pharma Chemica received 11575 citations as per Google Scholar report

Der Pharma Chemica peer review process verified at publons

rokettube brazzers

Turkish dental care is known to be affordable compared to other countries. If you want an affordible dentist Turkey, check out periodonta. It is heavily recommended for dental patients visiting Turkey