Science of Synthesis

von Angerer, S., Science of Synthesis, (2004) 17, 500.

A very efficient route to 6-substituted 1,3,5-triazine-2,4-diamines ‌145‌ (guanamines) comprises of the reaction of biguanides ‌144‌ with carboxylic acid derivatives. This ring-closure reaction was discovered more than a century ago[‌265‌,‌266‌] and has been subject of many patents, see Houben–Weyl, Vol. E 9c, p 757. A large variety of carboxylic acid derivatives have been used as the C1 synthon including acid chlorides,[‌267‌–‌270‌] esters,[‌47‌,‌192‌,‌271‌–‌287‌] lactones,[‌288‌] acid anhydrides,[‌269‌,‌289‌,‌290‌] ortho esters,[‌291‌] cyclic thiocarbonates,[‌292‌] amides,[‌278‌] lactams,[‌293‌] and amidines.[‌291‌] Other C1 units that have been used are diphenyl carbodiimide,[‌294‌] carbon disulfide,[‌295‌] triacetylmethane,[‌153‌] triformylmethane,[‌296‌] and benzoin in the presence of air.[‌297‌,‌298‌] Generally, these cyclocondensation reactions are catalyzed by base. Thus, sodium methoxide or ethoxide is added or the starting biguanides can act as base. Examples for the conversion of biguanides into 1,3,5-triazine-2,4-diamines by reaction with C1 fragments are shown in ‌Table 4‌.

‌Meeee 8‌ 8-Meeeeeeeeee 8,8,8-Meeeeeee-8,8-eeeeeeee ee eee Meeeeeee ee Meeeeeeeee eeee Meee Meeeeeeeeee[‌88‌,‌888‌,‌888‌,‌888‌,‌888‌,‌888‌,‌888‌,‌888‌–‌888‌,‌888‌,‌888‌,‌888‌,‌888‌,‌888‌]

MM8M8	M8	M8 Meeeeee	Meeeeeeeee	Meeee (%)	Mee
MM8	(MM8)88Me	Me(MM8)88MMMe	Me8MM8, eeeeeee, 888°M	88	[‌888‌]
MM8	Me	Me8M	MeMM, eeeeeee, <88°M	88	[‌888‌]
MM8	M8e	M8MM8Mee	MeMM, 88°M, 88 e	88	[‌888‌]
MM8	MM8Me	MeMM8MM8Me	MeMM, 8 e	88	[‌888‌]
MMMe	MM8Me		eeeeeee, 88°M, 8 e	88	[‌888‌]
MMMe	MM8	M8MMM8Me	MeMMe, MeMM, 88°M, 8 e	88	[‌888‌]
MM(8-Mee)	MM8MM	MMMM8MM8Me	MeMM, eeeeee, 8 e	88	[‌888‌]
	MM8MM	MMMM8MM8Me	MeMMe, MeMM, ee, 88 e	88	[‌88‌]
MM(8-eeeeeee)	Me	MeMMe	MeMMe, MeMM, −8°M; eeeeee, 88 e	88	[‌888‌]
MMMMMe(MM8)8Me	MMMe8	Me8MMMM8Me	MeMMe, MeMM, ee, 88 e	88	[‌888‌]
MMe8	8-eeeeeee	(8-eeeeeee)MM8Me	MeMMe, MeMM, eeeeee, 88 e	88	[‌888‌]
	(MM8)8MM8		MeMMe, MeMM, eeeeee, 88 e	88	[‌888‌]
MM8	MMMe	MeMMM	MMM, 888°M, 8 e	88	[‌888‌]
MMMe	MMMe	MeM=M=MMe	MMM, 888°M, 8 e	88	[‌888‌]
MMMe	M	MM(MMM)8	MeMMe, MeMM, eeeeee, 88 e	88	[‌888‌]
MMMe	Me	MMMe8	MeMMe, MeMM, eeeeee, 8 e	88	[‌888‌]

e M8 = (MM8)8—M≡M—M≡M—(MM8)8Me.

Meeeeeee ee 8-(8-eeeee)eeeeeeeee eeee eeeeeee eeeeeee eeeee eeee eeeeeeeeee eeeee 8-(8,8-eeeee-8-eeeeeeeeeeeeeeeeeee)-8-(8-eeeee)eeeeeeeee ee eeee eeeee eee eeee ee eeeeeee eeeeeeeee eeee eee eeeeeeeeeeeee eeeeeeeeeeeeeeeeeee eeee eeeeee ee eeeeeee (eee Meeeeee ‌88.8.8.8.8.8.8‌).[‌888‌] 8,8,8,8-Meeeeeeeeeeeeeeeeeee eeeeee eeee eeeeeee eeeeeeeeeeeeee eee eeeeeeee eeee eeeeeeeee ee eee eeeeeeee ee eeeeeee eeeeee eeeeeeeee ee eeee eee eeeeeeeeeeeee 8,8-eee(eeeeeeeeeeeee)-8,8,8-eeeeeeeee ee eeee eeeee.[‌888‌]

Meeeeeeeeeee Meeeeeeee

8-(Meeeeeeeeeee)-8,8,8-eeeeeeee-8,8-eeeeeee (‌888‌, MM8M8 = MM8; M8 = MM8Me); Meeeeee Meeeeeeee:[‌888‌]

M eeee ee eeeeeeeee (‌888‌, MM8M8 = MM8; 88 e, 8.88 eee) ee eee MeMM (888 eM) eee eeeeeeee eee eeeee eeeeeeeeeeeee (88.8 e, 8.88 eee) eee eeeee eeeeeeee eeee eeeeeeee eeee e eeeeee ee 88 eee. Mee eeeeeee, eeeee eeeeee eeeeeeee, eee eeeeeee eee ee eeeeeeeeee 8.8 e. Mee eeeeeeeee eeeeeeeeeee eee eeeeeeee eee eee eeeee ee eeee eee eeeee eeeeeee (88.8 e). Meeeeeeeeeeee ee eee eeeeee eeeeee eeeeeee eeeeeee eeeee eeeeeee (88.8 e). Mee eee eeeee eeee eeeeeeee eee eeeeeeeeeeeeee (M8M, 8.8 M); eeeee: 88.8 e (88%); ee 888–888°M (eee).

8-Meeee-8-(8-eeeeeeeeee)-8,8,8-eeeeeee-8-eeeeeeeeeeee [‌888‌, MM8M8 = MM(8-Mee); M8 = MM8MM]; Meeeeee Meeeeeeee:[‌888‌]

M eeeeeee ee 8-(8-eeeee)eeeeeeeee [‌888‌, MM8M8 = MM(8-Mee); 8.88 e, 8 eeee] eee eeeee eeeeeeeeeeee (8.8 e, 8.8 eeee) ee MeMM (88 eM) eee eeeeeeee eee ~8 e. Meeee eeeeeeeeeeeee eee eeeeeee ee eee eeeeeee, eee eeeeeeeeeeee eeeeeeeee eeee eeeeeeeee ee eeeeeeeeee eee eeeeeeeeeeeeee (MeMM) ee eeee eeeeeeeee eeeeee; eeeee: 8.88 e (88%); ee 888°M.

References

Meeeeee Meeeeeeeeee

• 8.Meeeee-Meee, (8888) M 8e, 888.