Some introductory remarks to “In memoriam of Prof. Harry R. Hudson”

Phosphoros–the Morningstar, what a wonderful world came down to us through the millennia–let us keep and protect it! And Harry Hudson was able to wander between the worlds of arts and science as well. His advice in English history and literature was well accepted, like his profound knowledge in chemistry. We teamed up as partners in a group of chemists named EUROPHOS and combined our labs in London and in Düsseldorf with syntheses, analytics, structures, NMR spectroscopy and biological aspects. We enjoyed mutual visits, supported by binational funds, and looked into α-aminophosphonic acids, α-aminophosphinic acids and corresponding esters, generally abbreviated as NHR¹-CHR²-P(O)(R³)OR⁴. Selected results were published in a review, edited by V. Khukar and H. R. Hudson¹ and in several publications.^2a–j Molecular modelling, ring current calculations, and NMR were combined to understand complex ¹H NMR spectra of NHPh-CHPh-P(O(OEt)₂ and related structures.³ Compounds with sterically demanding substituents NH(CHPh₂)-CHR²-P(O(OEt)₂ (R² = Ph, Naphthyl, Anthranyl, Pyrenyl) were synthesized.^4a–b

Our particular interests were drawn toward the sterically overcrowded α-N-(diphenylmethyl)amino-α-(1-pyren-yl)methanephosphonic acid diethylester NH(CHPh₂)-CH(Pyr)-P(O(OEt)₂^4a which gave rise to a ¹H NMR spectrum⁵ (Figure 1) involving a total of 29 spins (Scheme 1):

Figure 1. 500 MHz-¹H-NMR-spectrum of α-N-(diphenylmethyl)amino-α-(1-pyrenyl)-methanephosphonic acid diethyl ester. Upper: experimental (3% in C₂D₂Cl₄, 300 K). Lower: simulated with WIN-DAISY. Two singlet lines: (a) C₂HDCl₄ (from C₂D₂Cl₄) at 6 ppm; (b) traces from acetone at 2.1 ppm.

Scheme 1. 29 spins of α-N-(diphenylmethyl)amino-α-(1-pyrenyl)methanepho-sphonic acid diethylester NH(CHPh₂)-CH(Pyr)-P(O(OEt)₂.

Only the pyrenyl fragment H₁ to H₉ (Figure 2) and neighboring protons H₁₀ and H₁₁ will be mentioned in more details within this foreword; more details are available in the literature^1,5:

Figure 2. 500 MHz-¹H-NMR-spectrum of α-N-(diphenylmethyl)amino-α-(1-pyrenyl)methanephosphonic acid diethyl ester at 300 K. Pyrene range (3% in CDCl₃, 300 K).

The pyrenyl part of this ¹H NMR spectrum may be broken down in a simplified first order approach (neglecting all the small interproton-couplings ⁿJ_HH with n > 3 and all ⁿJ_PH) into the superposition of one ABC and three AB type spectra. Those subsystems belong to: (a) H₁, H₂: AB; (b) H₅, H₇, H₆: ABC; (c) H₃, H₄: AB very close to A₂; (d) H₈, H₉: AB. Protons H₁ and H₉ and to a lesser degree H₂ and H₈ are affiliated with broadened lines possibly pointing toward dynamic exchange. Neighboring protons H₁₀ (CH) and H₁₁ (NH) show broadened lines as well. This might be due to ¹⁴N quadrupolar effects, long rang coupling to pyrenyl protons, or indicating again dynamics involving rotation around the pyrenyl-phosphorus bond. And indeed upon warming up to 403°K those broad lines sharpened up. Neglecting dynamics, a full line shape analysis and iteration using DAISY under WINNMR was performed, which yielded NMR parameters of 28 protons H₁ to H₂₈. Results for H₁ to H₁₁ are listed below in Table 1 (resonance frequencies, chemical shifts, spectral half widths) and in Table 2 (coupling constants). Data for the remaining protons H₁₂ to H₂₈ are given in Refs.^1,5

Table 1. Resonance frequencies ν_i, chemical shifts δ_i, and spectral half widths HW_i together with individual errors ±ϵ_i were obtained from iterating the 500 MHz-¹H-NMR-spectrum of α-N-(diphenylmethyl)amino-α-(1-pyrenyl)methanephosphonic acid diethylester at 300 K. Pyrene range. (3% in CDCl₃, 300 K, SW = 5170 Hz, NS = 64K, digital resolution: 0.079 Hz/pt corresponding 12.7 pts/Hz).

i Hi	Resonance Frequency	Error	Chemical Shift	Spectral half width	Error
i	νi [Hz]	±ϵi [Hz]	δi [ppm]	HWi [Hz]	±ϵi [Hz]
1	4207.886	0.731	8.399	40.157	1.595
2	4143.700	0.050	8.272	3.794	0.284
3	4067.908	0.178	8.125	0.713	0.858
4	4066.782	0.175	8.128	0.779	0.943
5	4119.262	0.013	8.230	0.794	0.043
6	4024.886	0.005	8.043	0.499	0.024
7	4100.666	0.016	8.196	0.847	0.037
8	3987.866	0.050	7.984	3.513	0.555
9	3898.960	1.239	7.956	58.764	3.540
10	2545.471	0.087	5.090	11.665	0.174
11	1474.95	n. i.	2.949	∼230	n. i.

R-Factor (%) = 1.244289. n.i.: not iterated.

Table 2. Coupling constants ⁿJ_ik (ⁿJ_HH and ⁿJ_PH) and individual errors ±ϵ_ik of α-N-(diphenylmethyl)amino-α-(1-pyrenyl)methanephosphonic acid diethylester.

Coupling constants					Error	Coupling constants					Error
Type	n	i	k	^nJik	±ϵik [Hz]	Type	n	i	k	^nJik	±ϵik [Hz]
HH	3	1	2	8.436	0.013	PH	7	3	29	1.054	0.086
HH	5	1	3	0.224	0.129	HH	4	4	5	−0.503	0.087
HH	6	1	4	−0.088	0.121	HH	5	4	6	−0.065	0.100
HH	8	1	5	0.154	0.034	HH	6	4	7	0.692	0.056
HH	9	1	6	0.072	0.045	HH	6	4	8	0.101	0.057
HH	8	1	7	0.458	0.022	HH	7	4	9	−0.704	0.094
HH	6	1	8	0.343	0.028	PH	8	4	29	−0.897	0.092
HH	5	1	9	5.000	0.018	HH	3	5	6	7.931	0.017
PH	4	1	29	4.910	2.172	HH	4	5	7	1.179	0.023
HH	4	2	3	−0.730	0.101	HH	6	5	8	0.279	0.027
HH	5	2	4	0.707	0.056	HH	7	5	9	0.267	0.036
HH	7	2	5	0.539	0.017	PH	8	5	29	0.626	0.045
HH	8	2	6	0.011	0.042	HH	3	6	7	7.601	0.017
HH	7	2	7	0.262	0.032	HH	5	6	8	0.009	0.036
HH	7	2	8	0.414	0.034	HH	6	6	9	0.177	0.039
HH	6	2	9	0.020	0.047	PH	9	6	29	0.389	0.022
HH	3	3	4	8.152	0.021	HH	4	7	8	−0.632	0.019
HH	5	3	5	0.312	0.080	HH	5	7	9	0.088	0.039
HH	6	3	6	0.462	0.069	PH	8	7	29	0.101	0.048
HH	7	3	7	−0.285	0.088	HH	3	8	9	8.767	0.074
HH	7	3	8	0.168	0.047	PH	6	8	29	−0.133	0.057
HH	6	3	9	0.978	0.135	PH	5	9	29	−2.632	0.352

(Experimental conditions given in Table 1.)

Data listed in Tables 1 and 2 are formal results obtained by line shape iteration. A few coupling constants are small, close to digital resolution, might be near to or equal to zero. ⁵J_HH of 5 Hz between protons H₁ and H₉ appears too large and not realistic, but it is the formal result and consequence from spectral half widths HW₁ = ca. 40 Hz and HW₉ = ca. 59 Hz. It is worth mentioning that ¹H NMR spectra of less crowded compounds α-N-(diphenylmethyl)amino-α-(1-Ar)methanephosphonic acid diethylester with Ar = Ph, Napthyl, and Anthranyl do not show those dyanamic phenomena. Hence spectral analysis of such systems is more simple.^1,5

Harry^{Figure 2} Hudson´s pyrenyl problem ended up in a thorough test of WIN-DAISY coming to the limits of iterability for complex multi spin systems, where fragment techniques, chemical, and magnetical equivalence in connection with fast line shape iterators were requested.^5,6

Toward the end of this foreword one more of Harry´s favourite structures should be mentioned: PNL62, which is the betainic form CH₃CH₂CH(NH₃⁺)PO₃H⁻ of the biorelevant α-aminopropanephosphonic acid CH₃CH₂CH(NH₂)PO₃H₂ and received considerable attention.^7a–f Dissociation and stability constants were determined followed by NMR controlled titrations leading to ion specific chemicals shifts δ_P. The HR ¹H NMR spectrum of CH₃CH₂CH(NH₃⁺)PO₃H⁻ was analyzed and iterated by automated lines shape procedures. And of course one side-question concerning the sign of coupling constant ²J_PH was settled by double resonance: the sign of ²J_PH is negative, while the sign of ³J_PH is positive. And this is true for related structures, a fact worth remembering when publishing on α-aminoalkylphosphonic acids and similar compounds.

Harry^{Table 1, Table 2} Hudson´s work was a catalyst for adjunct research, and we will not forget this fine, productive and pleasant cooperation.