Acta Chim. Slov. 2000, 47, 469-480.
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SIMPLE AND VERSATILE SYNTHESIS OF 2-ALKOXYALKYLAMINES
Jiri Zednik, Ladislav Leseticky, Stanislav Smrček
Department of Organic and Nuclear Chemistry, Charles University of Prague, Faculty of Science, Albertov 6, 128 40 Prague 2, Czech Republic
Received 14-08-2000
Abstract
Facile synthesis of 2-methoxyalkylnitriles and 2-ethoxyalkylnitriles and their reduction to amines for potential usage as isocyanide synthesis starting compounds is presented. Alkoxyalkylnitriles (methoxy and ethoxy) were prepared by reaction of corresponding dialkyl ketals and trimethylsilyl cyanide. This reaction was optimized for the highest yield and its usability was confirmed on series of dialkyl ketals. Following standard hydride reduction of appropriate methoxy or ethoxy nitriles gave corresponding methoxy or ethoxyamines. Identity and purity of all newly prepared compounds was confirmed by means of NMR spectroscopy.
Introduction
Complexes of 99mTc with aliphatic alkoxyalkylisocyanides are used as a very
powerful radiodiagnostics of heart disease.1-3 Various isocyanide ligands are applied for these purposes (mainly 2-methoxy-2-methylpropyl isocyanide4). The presence of an alkoxy group in the ligand molecule is strongly assumed to be essential for the optimal radiopharmaceutical properties of the resulting complex.3 Isocyanides are compounds with very unpleasant properties due to their limited stability and unpleasant odour.5 In contrast, salts of alkoxy amines (e.g. hydrochlorides or oxalates) are much more stable compounds. Since the conversion of amine to isocyanide is a simple reaction,5 it can be involved in the reaction sequence for the 99mTc isocyanide complex preparation just before diagnostic application.
Various synthetic approaches leading to corresponding amine precursors could be suggested. One of them is based on direct conversion of dialkyl ketals to alkoxyalkylnitrile for example via treatment of ketal with tert-butyl isocyanide using TiCl4 as a catalyst6 followed by standard hydride reduction7 of nitrile to amine.
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Modern approach to this method uses reaction of dialkyl ketals (mostly dimethylketals) of ketones with trimethylsilyl cyanide (TMSCN) using Lewis acid as a catalyst, e.g.: ZnI2, SnCl4, FeCl3, TiCl48,9 and FB3.Et2O.10-12
Results and discussion
In this contribution we report the modification of the latter synthetic method and its large-scale application for the preparation of ligand's precursors (2-alkoxyalkylamines).
R1	R1	OR3                 R1 /            TMSCN            \	OR3 /           LiAlH	R1	R1 \      ^O3
/          ° R2 Scheme 1.	R2	OR3                 R2	N	R2A CH2 / H2N	R2A CH2 / CN
At first, the 1-methoxycyclohexanecarbonitrile was synthesized via modification of published procedure10-12 from 1,1-dimethoxycyclohexane13 and TMSCN. Reaction was performed without solvent and the boron trifluoride aetherate was used as a catalyst.10-12 Modifying the reaction conditions, 1-ethoxycy-clohexanecarbonitrile was prepared per analogiam. The reaction conditions were optimized for the highest yield by varying of temperature and time (Table 1 and 2) and the wide reliability and applicability of this reaction was confirmed on the following substrates: 1,1-dimethoxycyclohexane, 1,1-diethoxycyclohexane, 1,1-dimethoxycyclopentane, 1,1-dimethoxycycloheptane, 1,1-diethoxycycloheptane, 1,1-dimethoxycyclooctane, 1,1-diethoxycyclooctane, 4,4-dimethoxyheptane, 3,3-dimethoxyheptane, 3,3-dimethoxypentane, 2,2-dimethoxy-3-methylbutane, 2,2-dimethoxy-4-methylpentane, 1, 1-dimethoxy-4-methylcyclo-hexane, 1,1-dimethoxy-3-methylcyclohexane. Resulting nitriles were always reduced by standard procedure using LiAlH4 in aether.7 By this manner, couples of mostly new nitriles and amines were prepared and characterized by NMR. Experimental
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Material and methods
Gas chromatograph Varian 3400 (30 m DB-5 J a W Scientific column) with mass
spectrometer the Incos 50 Finnigan MAT (temperature of ion source was 150°C and energy of ionizating electrons was 75 eV) was used for GC-MS measurement. 1H NMR spectra were recorded on Varian UNITYINOVA 400 (400 MHz, FT mode). Chemical shifts are presented in d (ppm). In CDCl3, the scale (d, ppm) was referenced to tetramethylsilane, in D6-DMSO to DMSO signal (d=2.50) and in D2O to HDO (d=4.70) signal or to internal standard, 2-methyl-2-propanole (d=1.25). 13C NMR spectra were recorded on the same instrument, Varian UNITYINOVA 400 (100 MHz). The scale was referenced to the solvent signal (CDCl3, d=77.00), (D6-DMSO, d=39.50) and in D2O to 2-methyl-2-propanol (d=31.60).
Gas chromatography was performed on Varian Vista 6500 with 30 m capillary column DB-5 J a W Scientific and FID detector. Inlets were done splitless with w-decane as an external standard. For column preparative chromatography Kieselgel 60 Merck and for thin layer preparative chromatography Kieselgel 60 G were used.
All ketones (Lachema) used as starting compounds for synthesis were distilled before use. Solvents (Lachema) were distilled, dried and purified by standard laboratory methods. All dialkyl ketals from ketones were synthesized via standard treatment of trimethyl orthoformate or triethyl orthoformate using /?-toluensulfonic acid as an acidic catalyst.14 Samples for melting points were dried in oil pump vacuum for 72 h at 40oC (this long time is necessary, because there were problems with crystalline water). Melting points are not corrected. Elemental analyses were performed on Perkin Elmer 240 C elemental analyser.
General procedure
To  1  g of 1,1-dimethoxycyclohexane (6.94 mmol) in a round bottomed flask
equipped with a septum and a magnetic stirring bar 1.85 ml of TMSCN (13.88 mmol) was added in one portion. Mixture was cooled to 0°C and boron trifluoride aetherate (5 mol % with respect to dialkyl ketal) was added with microsyringe and the mixture was stirred for 1 hour at 0°C under nitrogen atmosphere. Then, 10 ml of water was added to the mixture (HCN (g) evolved from the reaction mixture.) After 12 h of stirring at room
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temperature, the rest of dissolved HCN was washed out with nitrogen. Aqueous phase was then extracted with 3 x 5 ml of dichloromethane. Combined organic layers were dried over MgSO4. After removing solvent in vacuum, the residual colourless oil was distilled at reduced pressure. Yield of isolated 1-methoxy-1-cyclohexanecarbonitrile was 0.79 g (82%). All other methoxy-alkylnitriles were prepared by the same manner. For preparation of all ethoxyalkylnitriles the reaction procedure was modified: reaction time was prolonged to 24 h and reaction temperature was enhanced to 25oC.
Alkoxynitriles were then reduced to amines using LiAlH4 in aether.7 All amines were isolated as oxalates and were crystallized from MeOH. After amine releasing with aqueous solution of NaOH (10 %) followed by extraction with diethyl aether, chromatography on silica gel (CHCl3: MeOH: NH4OH (aq. 25 %) / 6: 4: 0.1) was used in the case when further purification was necessary.
Results
Optimisation of yield for reaction of dimethyl and diethyl ketal and TMSCN was performed by using GC. Starting ketone, dialkyl ketal, and ketone cyanhydrine was present in reaction mixture. We found that amount of impurities is mostly temperature and time dependent. The yields of main products in different temperatures are presented in the following tables.
Table 1. Optimisation of reaction conditions for 1-methoxycyclohexanecarbonitrile (GC-yields in %)___________________________________________________________
Temp. (oC)/time	15 min	1 h	3 h	6 h	12 h	24 h	48 h
0 25	82 34	92 37	92 42	91 40	90 38	88 32	81 26
J. Zednik, L. Leseticky, S. Smrček: Simple and Versatile Synthesis of 2-Alkoxyalkylamines
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Table 2. Optimisation of reaction conditions for 1-ethoxycyclohexanecarbonitrile (GC-yields in %)___________________________________________________________
Temp.   15 min   lh    3 h    6 h    12 h    24 h    48 h (°C)/time
0 2 4 10 15 22 31 34 25 6 10 18 36 48 57 66 50     12     22     26     40     38     32     18
Table 3. Nitriles and their spectral data______________________
Compound             Yield                              Spectral data
Colourless oil - boiling point: 74 - 78°C (2 kPa), 83     Anal.: Calculated for C9Hi5NO: C, 70.55; H, 9.87; N, 9.14; O, 10.44. Found: C, 70.95; H, 10.01; N, 9.03. XH NMR (CDC13): 1.25 (t, 3H, J=6.9, CH3); 1.50 - 1.80 (m, 6H); 2.08 (m, 4H), (5 x CH2); 3.66 (q, 2H, J=6.9, OCH2). 13C NMR (CDCls): 15.20 (CH3); 22.34 (C3>5); 24.63 (C4); 37.63 (C2;6); 60.43 (OCH2); 69.35
(Ci); 121.92 (CN).    _______________________
Colourless oil - boiling point: 58-62°C (2 kPa), 82     Anal.: Calculated for C7HnNO: C, 67.17; H, 8.86; N, 11.19; O, 12.78. Found: C, 68.01; H, 8.52; N, 12.04. XH NMR (CDC13): 1.68 (m, 4H, 2 x CH2); 1.97 (m, 4H, 2 x CH2); 3.29 s, 3H, (OCH3). 13C NMR (CDCI3): 22.67 (C3>4); 37.14 (C2,5); 53.20 (OCH3); 79.93 (CQ; CN (119.83). Colourless oil - boiling point: 95-97°C (2 kPa), 85     Anal.: Calculated for C9Hi5NO: C, 70.55; H, 9.87; N, 9.14; O, 10.44. Found: 70.02; H, 9.64; N, 9.89. XH NMR (CDC13): 1.50 (m, 8H; 1.82 m, 2H; 1.96 m, 2H, 6 x CH2); 3.27 s, 3H, (OCH3). 13C NMR (CDCI3): 21.07 (C3>6); 27.81 (C4>5); 37.38 (C2;7); 52.62 (OCH3), 78.11 (Ci), CN (120.51).
1-Ethoxycyclohexanecarbonitrile
1 -Methoxycyclopentane-carbonitrile15
1 -Methoxycycloheptane-carbonitrile
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Table 3 Continued.
1-Ethoxycycloheptane-carbonitrile
1 -Methoxycyclooktane-carbonitrile
1 -Ethoxycyclooctane-carbonitrile
2-Methoxy-2-propylpentanenitrile
Colourless oil - boiling point: 122-124°C (2 kPa),
80     Anal: Calculated for CioHnNO: C, 71.81; H. 10.25; N, 8.37; O, 9.57. Found: C, 72.11; H, 10.19; N, 8.42. XH NMR (CDC13): 1.23 (t, 3H, J = 7.0, CH3); 1.64 (m, 8H, 4 x CH2); 1.96 (m, 2H, CH2); 2.10 (m, 2H, CH2); 3.62 (q, 2H, J=7.0, OCH2). 13C NMR (CDCls): 15.31 (CH3); 21.31 (C3)6); 28.01 (C4)5); 38.10 (C2;7); 60.94 (OCH2),
77.64 (Ci); 121.25 (CN).____________________
Colourless oil - boiling point: 120-124°C (2 kPa),
88    Anal.: Calculated for CioHnNO: C, 71.81; H, 10.25; N, 8.37; O, 9.57. Found: C, 72.03; H, 10.03; N, 8.41. XH NMR (CDC13): 1.59 (m, 10H); 2.04 (m, 4H), (7 x CH2); 3.41 (s, 3H, OCH3). 13C NMR (CDCI3): 20.64 (C3>7); 24.12 (C5); 27.48 (C4)6); 32.33 (C2;8); 52.67 (OCH3); 78.22 (d);
120.45 (CN).______________________________
Colourless oil - boiling point: 162-166°C (2 kPa),
88     Anal.: Calculated for C11H19NO: C, 72.88; H, 10.56; N, 7.73; O, 8.83. Found: C, 73.01; H, 10.32; N, 7.62. XH NMR (CDC13): 1.23 (t, 3H, J = 7.0, CH3); 1.57 (m, 8H); 1.70 (m, 2H); 2.03 (m, 4H), (7 x CH2); 3.61 (q, 2H, J=7.0, OCH2); 13C NMR (CDCI3): 15.31 (CH3); 20.76 (C3>7); 24.19 (C5); 27.59 (C4)6); 32.92 (C2;8); 60.83
(CH2); 77.61 (CQ; 121.05 (CN).______________
Colourless oil - boiling point: 84-86°C (2 kPa),
82     Anal.: Calculated for C9Hi7NO: C, 69.63; H, 11.04; N, 9.02; O, 10.31. Found: C, 70.01; H, 11.05; N, 9.12. XH NMR (CDC13): 0.97 (t, 6H, J=6.8, 2 x CH3); 1.47 (m, 4H); 1.74 (m, 4H), (4 x CH2); 3.41 (s, 3H, OCH3). 13C NMR (CDC13): 13.94 (C5)3’); 16.82 (C4)20; 38.17 (C3,r); 52.90 (OCH3); 78.12 (C2); 119.61 (CN)._____________
2-Ethyl-2-methoxyhexanenitrile
84
Colourless oil - boiling point: 89-91°C (2 kPa), Anal: Calculated for C9Hi7NO: C, 69.63; H, 11.04; N, 9.02; O, 10.31. Found: C, 69.52, H, 11.12; N, 9.52. XH NMR (CDC13): 0.94 (t, 3 H, J=7.2, CH3); 1.01 (t, 3H, J=7.3, CH3); 1.39 (m, 4H, 2 x CH2); 1.75 (m, 2H, CH2); 1.82 (q, 2H, J=7.5, CH2); 3.41 (s, 3H, OCH3).  13C NMR (CDCI3): 7.70 (C2O; 13.85 (C6); 22.59 (C5); 25.44 (C4); 28.95 (Cr); 35.22 (C3); 52.91 (OCH3); 78.68 (C2); 119.56 (CN).____________________
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Table 3 Continued.
Colourless oil - boiling point 79-81 °C (2 kPa), 2-Methoxy-2,3-                     89     Anal.: Calculated for C7H13NO: C, 66.10; H,
dimethylbutanenitrile                      10.30; N, 11.01; O, 12.58. Found: C, 66.71; H,
11.00; N, 11.02. XH NMR (CDCI3): 1.02 (d, 3H, J=6.8, CH3-CH); 1.07 (d, 3H J=6.8, CH3-CH); 1.45 (s, 3H, CH3); 2.02 (septet, 1H, J=6.8, CH); 3.43 (s, 3H, OCH3). 13C NMR (CDC13): 16.51, 17.23 (CH(CH3)2); 19.67 (C2-CH3); 35.98 (C3);
_______________________________52.98 (OCH3); 78.74 (C2); 119.50 (CN).________
Colourless oil - boiling point 62-65°C (2 kPa), 2-Methoxy-2,4-                     81     Anal.: Calculated for C8H15NO: C, 68.04; H,
dimethylpentanenitrile                     10.71; N. 9.92; O, 11.33. Found: C, 68.56; H,
10.82; N, 10.02. XH NMR (CDC13): 1.01 (d, 3H, J=6.4, CH3-CH); 1.02 (d, 3H, J=6.4, CH3-CH); 1.53 (s, 3H, CH3); 1.66 (dd, 1H, Ji=14.4, J2=6.3) and 1.72 (dd, 1H, Ji=14.4, J2=6.3), (CH2); 1.94 (septet, 1H, J=6.6, CH). 13C NMR (CDCI3): 23.60, 23.67 (CH(CH3)2); 24.15 (C2-CH3); 24.57 (C4); 47.99 (C3); 52.85
_______________________________(OCH3); 74.29 (C2); 120.12 (CN).______________
Colourless oil - boiling point: 78-82°C (2 kPa), l-Methoxy-4-methyl-        88     Anal: Calculated for C9Hi5NO: C, 70.55; H, 9.87; cyclohexancarbonitrile                 n, 9.14; O, 10.44. Found: C, 70.72; H, 10.06; N,
9.29.1H NMR (CDC13): 0.95 (d, 3H, J=6.4, CH3); 1.28 (m, 2H); 1.47 (m, 2H); 1.79 (m, 2H), (3 x CH2); 2.21 (m, 3H, CH2 + CH); 3.44 (s, 3H, OCH3).13C NMR (CDCI3): 21.22 (CH3); 31.12 (C3)5); 33.01 (C4); 34.82 (C2;6), 52.29 (OCH3); 76.23 (Ci), 119.28 (CN).
Colourless oil - boiling point: 95-100°C (2 kPa), l-Methoxy-3-methyl-        95     Anal: Calculated for C9Hi5NO: C, 70.55; H, 9.87;
cyclohexancarbonitrile                 n, 9.14; O, 10.44. Found: C, 71.00; H, 9.91; N,
9.14. XH NMR (CDCI3) : 0.98 (d, 3H, J=6.2, CH3); 1.50 - 1.90 (m, 6 H); 2.20 (m, 3H); 3.44 (s, 3H, OCH3). 13C NMR (CDCI3): 21.53 (C5); 22.47 (CH3); 29.70 (C4); 33.32 (C6); 33.38 (C3); 34.72 (C2); 52.12 (OCH3); 76.43 (Ci); 119.41
_____________________________(CN>_______________________________________
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Table 4. Amine hydrogen oxalates and their spectral data.
Compound
Yield
Spectral data
(1 -Methoxycyclohexyl)-methanamine
86
(1 -Ethoxycyclohexyl)-methanamine
79
White crystalline solid - melting point: 157-162°C (recryst. methanol), Anal.: Calculated for CioHi9N05: C, 51.49; H, 8.21; N, 6.00; O, 34.29. Found: C, 52.11; H, 8.44; N, 5.89. 'H NMR (D6-DMSO): 1.20 - 1.80 (m, 10H, 5 x CH2); 2.68 (s, 2H, CH2N); 3.17 (s, 3H, OCH3). 13C NMR (D6-DMSO): 21.65 (C3’,5’); 25.92 (C40; 31.72 (C2<;6<); 45.69 (CH2N); 48.11 (OCH3); 75.01 (Cr); 164.79
(oxalate)._________________________________
White crystalline solid - melting point: 138-142°C (recryst. methanol), Anal.: Calculated for CnH2iN05: C, 53.43; H, 8.56; N, 5.66; O, 32.35. Found C, 53.82; H, 8.62; N, 5.78. XH NMR (D6-DMSO): 1.12 (t, 3H, J=6.9, CH3); 1.20 - 1.72 (m, 10 H, 5 x CH2); 2.85 (s, 2H, CH2N); 3.29 (q, 2H, J=6.9, OCH2). 13C NMR (D6-DMSO): 15.54 (CH3); 21.20 (C3’)50; 25.20 (C40; 34.54 (C^O; 42.69 (CH2N); 55.20 (OCH2); 72.63 (Cr); 164.67 (oxalate)._________________________________
(1 -Methoxycyclopentyl)-methanamine
79
White crystalline solid - melting point: 160-164°C (recryst. methanol), Anal.: Calculated for C9Hi7N05: C, 49.31; H, 7.82; N, 6.39; O, 36.49. Found: C, 49.92; H, 7.72; N, 6.48. XH NMR (D6-DMSO): 1.56 (m, 6H, 3 x CH2); 1.77 (m, 2H, CH2); 2.97 (s, 2H, CH2N); 3.08 (s, 3H, OCH3). 13C NMR (D6-DMSO): 23.27 (C3’,4’); 33.04 (C2<;5<); 42.56 (CH2N); 49.36 (OCH3); 84.02 (Cr); 168.24 (oxalate).______________________
(1 -Methoxycycloheptyl)-methanamine
79
White crystalline solid - melting point: 142-144°C (recryst. methanol), Anal.: Calculated for CnH2iN05: C, 53.43; H, 8.56; N, 5.66; O 32.35. Found: C, 53.92; H, 8.66; N, 5.72. XH NMR (D6-DMSO): 1.43 (m, 10H); 1.74 (m, 2H), (6 x CH2); 2.86 (s, 2H, CH2N); 3.09 (s, 3H, OCH3). 13C NMR (D6-DMSO): 21.38 (C3<;6<); 29.13 (C4.,sO; 33.92 (C2’,t); 43.18 (CH2N); 48.62 (OCH3); 76.83 (Cr); 163.92 (oxalate).__________
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Table 4 Continued.
(1 -Ethoxycycloheptyl)-methanamine
89
(1 -Methoxycyclooctyl)-methanamine
89
(1 -Ethoxycyclooctyl)-methanamine
87
2-Methoxy-2-propyl-1 -pentanamine
62
White crystalline solid - melting point 128-132°C (recryst. methanol), Anal.: Calculated for Ci2H23N05: C, 55.16; H, 8.87; N, 5.36; O, 30.61. Found: C, 55.52; H, 8.67; N, 5.28. XH NMR (D6-DMSO): 1.10 (t, 3H, J=6.8, CH3); 1.46 (m, 10H, 5 x CH2); 1.75 (m, 2H, CH2); 2.85 (s, 2H, CH2N); 3.31 (q, 2H, J=6.8, OCH2). 13C NMR (D6-DMSO): 15.62 (CH3); 21.40 (C3<;6<); 29.06 (C4’,50; 34.53 (C2’,t); 43.82 (CH2N); 55.75
(OCH2); 76.65 (Cr); 165.55 (oxalate).__________
White crystalline solid - melting point 142-145°C (recryst. methanol), Anal.: Calculated for Ci2H23N05: C, 55.16, H, 8.87; N, 5.36; O, 30.61. Found: C, 55.42; H, 8.62; N, 5.38. XH NMR (D6-DMSO): 1.48 (m, 12H, 6 x CH2); 1.73 (m, 2H, CH2); 2.85 (s, 2H, CH2N); 3.06 (s, 3H, OCH3). 13C NMR (D6-DMSO): 20.74 (Cr,T); 24.21 (CsO; 27.58 (C4’,6’); 29.11 (C2’,80; 41.31 (CH2N);
48.58 (OCH3); 76.26 (Cr), 164.26 (oxalate). White crystalline solid - melting point 138-142°C (recryst. methanol), Anal.: Calculated for Ci3H25N05: C, 56.71; H, 9.15; N, 5.09; O, 29.05. Found: C, 57.01; H, 9.02; N, 5.00. XH NMR (D6-DMSO): 1.09 (t, 3H, J=7.0, CH3); 1.48 (m, 12 H); 1.74 (m, 2H), (7 x CH2); 2.84 (s, 2H, CH2N); 3.28 (q, 2H, J=7.0, OCH2). 13C NMR (D6-DMSO): 15.52 (CH3); 20.72 (Cy,T); 24.16 (C50;
27.59 (C4’,60; 29.52 (C2.,80; 42.05 (CH2N); 55.71 (OCH2); 76.10 (Cr), 164.46 (oxalate).
White crystalline solid - melting point 115-120°C (recryst. methanol), Anal.: Calculated for C-nH23N05: C, 52.99; H, 9.30; N, 5.62; O, 32.09. Found: C, 53.02; H, 9.25; N, 5.72. XH NMR (D6-DMSO): 0.87 (t, 6H, J=7.3, 2 x CH3); 1.19 (m, 4H); 1.40 (m, 4H), (4 x CH2); 2.82 (s, 2H, CH2N); 3.07 (s, 3H, OCH3). 13C NMR (D6-DMSO): 14.24 (C5;30; 15.83 (C4)20; 33.99 (C3,r); 40.85 (CH2N); 48.27 (OCH3); 76.03 (C2); 164.58 (oxalate)._________________________________
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Table 4 Continued.
2-Ethyl-2-methoxy-1-hexanamine
64
2-Ethyl-2-methoxy-1-butanamine
68
White crystalline solid - melting point 115-119°C (recryst. methanol), Anal.: Calculated for C-nH23N05: C, 52.99; H, 9.30; N, 5.62; O, 32.09. Found: C, 53.12; H, 9.45; N, 5.63. 'H NMR (D6-DMSO): 0.77 (t, 3H, J=7.5, CH3); 0.88 (t, 3H, J=7.3, CH3); 1.10 - 1.50 (m, 8H, 4 x CH2); 2.83 (s, 2H, CH2N); 3.07 (s, 3H, OCH3). 13C NMR (D6-DMSO): 7.29 (C2<); 13.86 (C6); 22.48 (C5); 24.22 (C4); 24.49 (Cr); 30.82 (C3); 40.40 (CH2N); 48.28 (OCH3); 76.27 (C2); 164.35
(oxalate).____________________________________
White crystalline solid - melting point 107-110°C (recryst. methanol), Anal.: C9Hi9N05: C, 48.86; H, 8.66; N, 6.33, O, 36.16. Found: C, 48.84; H, 8.42; N, 6.42. XH NMR (D6-DMSO): 0.77 (t, 6H, J=7.4, 2 x CH3); 1.47 (m, 4H, 2 x CH2); 2.83 (s, 2H, CH2N); 3.08 (s, 3H, OCH3). 13C NMR (D6-DMSO): 7.18 (C2<;4); 23.64 (Cr,3); 40.00 (CH2N); 48.28 (OCH3); 76.50 (C2), 163.91 (oxalate).
2-Methoxy-2,3-dimethyl-1-butanamine
65
2-Methoxy-2,4-dimethyl-1-pentanamine
68
White crystalline solid - melting point 135-139°C (recryst. methanol), Anal.: Calculated for C9Hi9N05: C, 48.86; H, 8.66; N, 6.33; O, 36.16. Found: C, 49.11; H, 8.52; N, 6.21. XH NMR (D6-DMSO): 0.82 (d, 3H, J=6.8); 0.84 (d, 3H, J=6.8); 1.06 (s, 3H), (3 x CH3); 1.95 (septet, 1H, J = 6.8, CH); 2.87 (s, 2H, CH2N); 3.10 (s, 3H, OCH3). 13C NMR (D6-DMSO): 16.25, 16.48, 16.82 (3 x CH3); 31.15 (C3); 41.58 (Ci); 48.53 (C2); 76.37
(OCH3), 164.15 (oxalate).______________________
White crystalline solid - melting point 115-119°C (recryst. methanol), Anal.: Calculated for CioH2iN05: C, 51.05; H, 9.00; N, 5.95; O, 34.00. Found: C, 51.03; H, 9.10; N, 6.05. 'H NMR (D6-DMSO): 0.91 (d, 3H, J=6.8); 0.92 (d, 3H, J=6.8); 1.15 (s, 3H), (3 x CH3); 1.40 (m, 2H, CH2); 1.70 (septet, 1H, J=6.8, CH); 2.85 (s, 1H, CH2N); 3.09 (s, 3H, OCH3).
13C NMR (D6-DMSO): 20.32 (C2-CH3); 24.05, 24.14 (CH(CH3)2); 23.06 (C4); 42.83 (C3); 44.64 (Ci); 48.80 (OCH3); 74.49 (C2); 167.25 (oxalate).
J. Zednik, L. Leseticky, S. Smrček: Simple and Versatile Synthesis of 2-Alkoxyalkylamines
Acta Chim. Slov. 2000, 47, 469-480.
479
Table 4 Continued.
White crystalline solid - melting point 142-145°C (l-Methoxy-4-methyl-          72     (recryst. methanol), Anal.: Calculated for
cyclohexyl)methanamine               CnH2iN05: C, 53.43; H, 8.56; N, 5.66; O, 32.35.
Found: C, 53.98; H, 8.32; N, 5.44. 1H NMR (D6-
DMSO): 0.82 (d, 3H, J=6.3, CH3); 1.50 (m, 9H);
2.31 (s, 2 H, CH2N); 3.12 (s, 3 H, OCH3). 13C
NMR (D6-DMSO): 22.13 (CH3); 29.45 (C3<;5<);
32.84 (C2’,6’); 37.28 (C40; 47.25 (CH2N); 51.27 ____________________________(OCH3); 74.23 (Cr), 166.28 (oxalate)._________
White crystalline solid - melting point 104-109°C (1 -Methoxy-3-methyl-        69     (recryst. methanol), Anal.: Calculated for cyclohexyl)methanamine              CnH2iN05: C, 53.43; H, 8.56; N, 5.66; O, 32.35.
Found: C, 52.99; H, 8.50; N, 5.70. 1H NMR (D6-
DMSO) : 0.86 (d, 3H, J=6.3, CH3); 1.50 (m, 9H);
2.98 (s, 2H, CH2N); 3.12 (s, 3H, OCH3). 13C
NMR (D6-DMSO): 21.95 (C50; 22.30 (CH3);
28.69 (C40; 30.80 (C3<); 33.71 (C60; 39.62 (Cr);
40.13 (CH2N); 47.20 (OCH3), 74.20 (Cr) 165.29 ____________________________(oxalate).________________________________
References
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J. Zednik, L. Leseticky, S. Smrček: Simple and Versatile Synthesis of 2-Alkoxyalkylamines
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Acta Chim. Slov. 2000, 47, 469-480.
Povzetek
Opisana je enostavna sinteza 2-metoksialkilnitrilov in 2-etoksialkilnitrilov, njihova redukcija do aminov ter potencialna uporaba le-teh v sintezi izocianidov. Sinteza je potekla iz ustreznih dialkilketalov in trimetilsilil cianida. Reakcijski pogoji so bili optimizirani za dosego največjega izkoristka. S standardno redukcijo s hidridi so bili pripravljeni metoksi oziroma etoksiamini. Strukture novih spojin so bile potrjene z NMR spektroskopijo.
J. Zednik, L. Leseticky, S. Smrček: Simple and Versatile Synthesis of 2-Alkoxyalkylamines