Table 1.

Comparison of classic and green methods for the preparation of CD derivatives.

Entry	Compound	Reagent/solvent	Reagent/ halogen molar ratio	Method	Batch size [mmol]	Yielda [%]	Final temp. [°C]	React. time [h]
1	3a	thiourea/DMF	2	soln.	7.5	75	80	3 [27]
2		thiourea	1.5	BM	0.1	12	89	2
3		thiourea	3.5	BM	0.1	25	89	2
4		thiourea	3.5	BM	1	61	88	2
5		thioureab	3.5	BM	0.1	tracesc	92	2
6	3b	thiourea/DMF	2	soln.	5	90	80	16
7		thiourea	1.5	BM	0.1	14c,d	85	2
8		thioureae	1.5	BM	0.1	9c,d	82	2
9		thiourea	3.5	BM	0.05	33d	85	2
10		thioureae	3.5	BM	0.05	39d	82	2
11		thioureae	3.5	BM	0.5	57d	86	2
12	4a	NaN3/DMF	1.25	soln.	5	90	100–105	~4.5
13		NaN3/DMF	1.25	soln.	0.5	76	100–105	5
14		NaN3/DMFb	1.25	soln.	0.5	tracesc	100–105	5 [24]
15		NaN3b	5	BM	0.1	tracesc	86	2
16		NaN3	5	BM	0.1	69	88	2
17		NaN3	5	BM	0.5	72	90	2
18	4b	NaN3/DMF	1.25	soln.	5	84	100–105	≈4.5
19		NaN3	10	BM	0.05	67	82	2
20		NaN3	10	BM	0.5	71	84	2
21	5a	MPA/Cs2CO3/DMF	1.5	soln.	5	60	50	25 [28]
22		MPA/KOt-Buf	1.43	BM	0.1	86	72	2
23		MPA/KOt-Bu	1.5	BM	1	71	75	2
24	5b	MPA/NaH/DMF	1.25	soln.	1.4	60	70	12 [16]
25		MPA/TEA/DMFf	3	soln.	2.5	60c	60	24
26		MPA/KOt-Bu	1.25	BM	0.05	81	73	2
27		MPA/KOt-Bue	1.5	BM	0.05	86	71	2
28		MPA/KOt-Bue	1.5	BM	0.5	72d	76	2
29	6	DDS/K t-Bu/DMF	no data	soln.	1	>90	80	96 [29]
30		DDS/KOt-Bu/DMFg	3	soln.	0.5	83	80	120
31		DDS/KOt-Bug	1.6	BM	0.1	95	62	2

^aIsolated yields but due to small batch-sizes and not optimized purifications the yields of BM reactions are informative only. ^bFrom per-6-chloro-β-CD. ^cContains also incompletely substituted structures, further isolation/purification were not performed. ^dThe mother liquor contained considerable amounts of product by TLC. ^eFrom per-6-bromo-γ-CD. ^fMPA: 3-mercaptopropionic acid; TEA: N,N,N-triethylamine; KOt-Bu: potassium tert-butoxide; KOt-Bu/MPA molar ratio ≈2.1:1.;^gDDS: 1-dodecanethiol; DDS/KOt-Bu molar ratio 1:1.