KBS30-1 - N-alkylation with KBS29

[KlementineJBS]

Link to HIRAC and master page.

KBS30 - Generic alkylation of 1,x-diaminoalkane with naphthalene-triazole pendant (updated).docx

Reaction scheme

[KlementineJBS]

13.02.23

1. Dissolved 1,6-diaminohexane (41.3 mg, 0.356 mmol, 0.5 equiv) in MeCN (5 mL)
2. Added potassium carbonate (45.6 mg, 0.330 mmol, 0.5 equiv.)
3. Stirred at rt for 10 minutes
4. Cooled to 0 C
5. Added KBS29 (197 mg, 0.684 mmol) dissolved in MeCN (2.5 mL) dropwise over 1 hr
6. Took off after about 2 hrs stirring, TLC suggested SM was gone but multiple products formed

Left = ammonium hydroxide:methanol:DCM, 1:9:10; right = ammonium hydroxide:methanol:chloroform, 1:19:80

7. Filtered off gummy ochre solid
8. Washed with brine
9. Blew off solvent with N2 overnight (didn't want to risk promoting further reaction with heat from rotovap bath)

Obtained a pale crystalline substance.

[KlementineJBS]

15.02.23

LRMS

Evidence of bis, tris and tetra coupled products ([M+H]+) at 531.28, 738.41, 945.45.

KBS30-1 crude.pdf
KBS30-1 crude.d.zip

[KlementineJBS]

23.02.23

1:9:90 of NH4OH:MeOH:DCM

Variations of MeOH, CHCl3 and sometimes NH4OH

[KlementineJBS]

01.03.23

Fractions	Vial tare	Mass	Mass spec peaks	Data	Products
1-2	15.8061	12.4	738.38, 967.47, 1152.65	KBS30-1 F1-2.pdf	Tris, tetra
3-9	15.8318	30.9	680.83, (738.37), 945.53, 1152.62, 1753.68, 1845.77	KBS30-1 F3-9.pdf	Tris, tetra
10-11	15.8235	2.1	-	nil	unknown
12-16	15.7496	19	473.23, 531.29, 577.27, 680.81, 738.43, 945.54	KBS30-1 F12-16.pdf	Bis, tris, tetra
17-20	15.7525	18.8	531.34, 576.78, 680.83, 738.40, (945.52), 1741.94, 1841.81	KBS30-1 F17-20.pdf	Bis, tris, (tetra?)
21-24	16.0535	6.5	369.66, 403.16, 433.15, 531.31, 576.77, 738.39	KBS30-1 F21-24.pdf	Bis, tris

LRMS data

KBS30-1 F 1-24.d.zip

[KlementineJBS]

Uploading KBS30-1 F3-9 bleach.1.zip…

[KlementineJBS]

15.03.23

LRMS

Notes: +757 from previous user, tried to flush out with MeOH but not budging

531 or 576 = bis, 738 = tris, 945 = tetra

KBS30-1 RP F2-5.d.zip
KBS30-1 RP F6-11.d.zip

KBS30-1 RP F2.pdf - 576 (possibly bis), 738, 945
KBS30-1 RP F4-5.pdf - 531 (weak), 738, 945, 631, 759
KBS30-1 RP F6.pdf - 576 (weak), 738 (strong), 945
KBS30-1 RP F7-11.pdf - 680, 945 (weak)

• tetra compound may not have all come off column OR may not be present in a large quantity

[KlementineJBS]

[KlementineJBS]

22.03.23

RP column showed some promise but still failed to separate sufficiently. Will retry with a shallower gradient or potentially swap to HPLC.

All fractions were basified with sodium carbonate (10 mL), extracted with DCM (3 x 20 mL) and washed with brine or dried over mag sulphate before being NMR'd. NMR showed no clear sign of what was present - all had a large boc peak and other peaks were faint and/or indistinct.

KBS30 RP fractions.pdf

KBS30-1 RP F2_1.zip
KBS30-1 F4-5_1.zip
KBS30-1 RP F6_1.zip
KBS30-1 RP F7-11_1.zip