Synthesis of phosphonates from phenylphosphonic acid and its monoesters

Figures & data

Scheme 1. Earlier method for the synthesis of dialkyl phenylphosphonates.^[9]

Table 1. Direct esterification of phenylphosphonic acid with different alcohols under MW conditions.

R	IL	T (°C)	t (h)	Conversion^a (%)	Composition^a		Yield of the monoester (%)	Ref.	Entry
					Monoester 2 (%)	Diester 3 (%)
Bu	–	200	4^b	83	92 (2a)	8 (3a)	75 (2a)	^[Citation9]	1
Bu	10% [bmim][BF4]	180	0.75	100^c	95 (2a)	5 (3a)	82 (2a)	^[Citation10]	2
Et	–	165	8	30	98 (2a)	2 (3a)			3
Et	10% [bmim][BF4]	165	8	82	94 (2b)	6 (3b)	70 (2b)		4
Oct	–	220	4	96	75 (2c)	25 (3c)	–	^[Citation9]	5
Oct	10% [bmim][BF4]	180	0.75	100	96 (2c)	4 (3c)	90 (2c)	^[Citation10]	6

^a On the basis of relative ³¹P NMR intensities.

^b No change in the conversion on further irradiation.

^c In a comparative thermal experiment, the conversion was 22% [composition: 93% (2a) and 7% (3a)].

Table 2. Attempted monoalkylation of phenylphosphonic acid with butyl bromide under different conditions.

Base	PTC	T (°C)	t (h)	Conversion^a (%)	Composition^a		Entry
					Monoester 2a (%)	Diester 3a (%)
Et3N	–	80 (MW)	4	58	76	24	1
		80 (Δ)	4	47	85	15	2
		100 (MW)	2^b	62	61	39	3
K2CO3	TEBAC (5%)	80 (MW)^c	4	7	71	29	4

^a Based on relative ³¹P NMR intensities.

^b No change on further irradiation.

^c There was no reaction in the comparative thermal experiment.

Table 3. Attempted dialkylation of phenylphosphonic acid with butyl bromide under different conditions.

Base	PTC	BuBr (equiv.)	T (°C)	Conversion^a (%)	Composition^a		Yield of the diester (%)	Entry
					Monoester 2a (%)	Diester 3a (%)
Et3N	–	2.2	100	95	32	68		1
		2.2	120	94	35	65		2
		2.2	150	94	39	61		3
		5	120	100	17	83	69 (3a)	4
K2CO3	TEBAC (5%)	2.2	120	11	73	27		5

^a Based on relative ³¹P NMR intensities.

Table 4. Direct esterification of phenylphosphonic monoesters.

R	IL	T (°C)	t (h)	Conversion^a^,b (%)	Entry
Bu (2a)	–	180	6	7 (3a)	1
	–	220	6	17 (3a)	2
	10% [bmim][BF4]^c	220	6	45 (3a)	3
	10% [bmim][PF6]	220	6	40 (3a)	4
Oct (2c)	–	200	6	22 (3c)	5
	–	220	6	27 (3c)	6
	–	235	6	28 (3c)	7
	10% [bmim][BF4]^c	235	3	72 (3c)	8
	10% [bmim][PF6]	235	3	65 (3c)	9

^a Based on relative ³¹P NMR intensities.

^b Average of three parallel measurements.

^c No increase on further irradiation.

Table 5. Synthesis of dialkyl phenylphosphonates by the alkylation of phenylphosphonic monoesters.

R	RX	Base	Solvent	PTC	T (°C)	t (h)	Yield (%)	Entry
Bu (2a)	BuBr	Et3N	–	–	85^b	0.5^a	80 (3a)	1
		K2CO3	MeCN	TEBAC (5%)	100	1^a	75 (3a)	2
Et (2b)	EtI	Et3N	–	–	85	0.5	92 (3b)	3
		K2CO3	MeCN	TEBAC (5%)	100	1^a	76 (3b)	4
Oct (2c)	OctBr	Et3N	–	–	100	1	72 (3c)	5
		K2CO3	MeCN	TEBAC (5%)	100	1	58 (3c)	6

^a No change on further irradiation.

^b In the comparative thermal experiment the yield was 57%.

Table 6. Synthesis of phenylphosphonates with different alkyl groups by the alkylation of phenylphosphonic monoesters.

R	R′X	Base	Solvent	PTC	T (°C)	t (h)	Yield (%)	Entry
Bu (2a)	EtI	Et3N	–	–	85^b	0.5	71 (3d)	1
		K2CO3	MeCN	TEBAC (5%)	100^b	1	62 (3d)	2
	^nPrBr	Et3N	–	–	85	0.5	68 (3e)	3
		K2CO3	MeCN	TEBAC (5%)	100	1	56 (3e)	4
	^iPrBr	Et3N	–	–	85	0.5^a	48 (3f)	5
		K2CO3	MeCN	TEBAC (5%)	100	1	38 (3f)	6
Et (2b)	^nPrBr	Et3N	–	–	85	0.5	72 (3g)	7
		K2CO3	MeCN	TEBAC (5%)	100	1	54 (3g)	8
	^iPrBr	Et3N	–	–	85	1	54 (3h)	9
		K2CO3	MeCN	TEBAC (5%)	100	1^a	37 (3h)	10
	BuBr	Et3N	–	–	85	0.5	72 (3d)	11
		K2CO3	MeCN	TEBAC (5%)	100	1	67 (3d)	12

^a No change on further irradiation.

^b Diethyl phenylphosphonate by-product was formed at a higher temperature.

Scheme 2. The new protocol elaborated for the synthesis of dialkyl phenylphosphonates.

Kiss, N. Z.; Mucsi, Z.; Böttger, É.; Drahos, L.; Keglevich, G. A Three-Step Conversion of Phenyl-1H-Phosphinic Acid to Dialkyl Phenylphosphonates Including Two Microwave-Assisted Direct Esterification Steps. Curr. Org. Synthesis 2014, 11, 767–772. doi:10.2174/1570179410666131212231130.

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Kiss, N. Z.; Keglevich, G. Direct Esterification of Phosphinic and Phosphonic Acids Enhanced by Ionic Liquid Additives. Pure Appl. Chem. 2019, 91, 59–65. doi:10.1515/pac-2018-1008.

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