Base-Catalyzed Hydrophosphination of Azobenzenes with Diarylphosphine Oxides: A Precise Construction of N-N-P Unit

Article abstract of DOI:10.1021/acs.joc.6b01210

Addition of diarylphosphine oxides to the N=N double bond of azobenzenes leads to the formation of the P-substituted hydrazines in up to 98% yield for 24 examples, and the formation of diphenylphosphinic amides was observed in three substrates. This strat

Full text of DOI:10.1021/acs.joc.6b01210

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Note
Base-Catalyzed Hydrophosphination of Azobenzenes with
Diarylphosphine Oxides: A Precise Construction of N-N-P Unit
Gang Hong, Xiaoyan Zhu, Chen Hu, Alfred Njasotapher Aruma, Shengying Wu, and Limin Wang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01210 • Publication Date (Web): 07 Jul 2016
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Base-Catalyzed Hydrophosphination of Azobenzenes with
Diarylphosphine Oxides: A Precise Construction of N-N-P Unit
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Gang Hong,† Xiaoyan Zhu,† Chen Hu,† Alfred Njasotapher Aruma,† Shengying Wu,*,†
and Limin Wang*,†
†Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China
University of Science and Technology, 130 Meilong Road, Shanghai 200237, P. R. China
Phone (fax): +86-21-64253881; E-mail: wanglimin@ecust.edu.cn; wsy1986wsy@126.com
ABSTRACT: Addition of diarylphosphine oxides to the N=N double bond of azobenzenes
leads to the formation of the P-substituted hydrazines in up to 98% yield for 24 examples
and the formation of diphenylphosphinic amides was observed in 3 substrates. This strategy
features tolerance of a wide range of functional groups, simple operation, and mild reaction
conditions. Specially, this method can be also applied to the gram-scale synthesis of the
product. A polar reaction mechanism is also proposed based on control experiments.
Recently, significant attention has been paid to organophosphorous compounds for their
wide application in organic synthesis, asymmetric catalysis, and medicinal chemistry.1
Some pharmaceutical compounds containing P(=O)-N bond are depicted in Scheme 1. Thus,
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various methods have been developed to prepare organophosphorous compounds including
the construction of C-P bond,2 S-P bond,3 and N-P bond,4 among which the formation of
N-P bond usually suffered from anaerobic reagents, the use of toxic and moisture sensitive
halides (RO)2P(O)Cl, and inert conditions. Thus, it is always valuable to achieve N-P bond
formation under milder conditions to update the existing methods.
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Scheme 1. Structure of Pharmaceutical Compounds with Phosphinic Amide Unit
Azobenzenes are important scaffolds and have been widely applied in such fields as organic
dyes, protein probes, chemosensors, and molecular machines due to their unique
properties.5 Thus, the preparation of these compounds is well developed considering the
broad utility of azobenzenes.6 In 2014, our group realized the ortho-C-H phosphonation of
azobenzenes using N=N double bond as directing group,2b which further expanded the
scope of steric azo compounds. Meanwhile, the cleavage of the N=N bond is valuable in
understanding the mechanism of dinitrogen fixation as well as developing new
transformations using azo compounds as synthon. In 2014, Xi group utilized the cleavage
N=N bond of azobenzenes to synthesize benzimidazole derivatives.7 In 2015, the same
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group reported a new method for the synthesis of quinolones from azobenzenes and allyl
bromides via N=N bond cleavage.8 Recently, our group realized direct synthesis of amide
compounds from azobenzenes and aroyl surrogates via radical process (Scheme 2).9
However, it is still highly desirable to further explore the utilities of azobenzenes. Herein,
we report a highly efficient method for the construction of N-N-P unit by reaction of
azobenzenes with diarylphosphine oxides. To the best of our knowledge, only a few cases
for the synthesis of P-substituted hydrazines were reported.10
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Scheme 2. Different Approaches for the Cleavage of N=N Double Bond
At the outset, based on our previous work,9 we envisaged that P-centered radical, generated
from diphenylphosphine oxide,11 could attack the N=N double bond. Subsequently, the
hydrolysis of the intermediate 3aa could afford the final product 4aa (Table 1). Our initial
efforts focused on the model reaction of azobenzene (1a) with diphenylphosphine oxide (2a)
to optimize the reaction condition. Unexpectedly, screening on the oxidant showed the use
of DTBP (tert-butyl peroxide) afforded 3aa in 76% yield, however our expected product
4aa was not observed (Table 1, entries 1-5). Encouraged by this result, we further optimized
the reaction conditions through adding base as additive and found that the use of base did
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increase the yield of 3aa, and Cs2CO3 enhanced the product 3aa yield up to 88% for 6 h
(Table 1, entries 6-8). Surprisingly, this reaction could proceed well even without oxidant,
affording 3aa in up to 96% yield (Table 1, entry 9). What’s more, 95% yield was obtained
when shortening the reaction time to only 30 minutes (Table 1, entry 10). Solvent screening
including DCE, DMSO, PhCl, and DMF revealed that these tested solvents were all inferior
in terms of the reaction yields (Table1, entries 11-14). Gratifyingly, the yield was increased
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to 98% when the temperature was decreased to 100 C (Table 1, entries 15 and 16). Also,
decreasing the amount of Cs2CO3 to 0.2 equiv led to 16% yield of the product (Table 1.
entry 17). The reaction did not proceed in the absence of Cs2CO3 (Table 1, entry 18). It
should be noted that the assumed product 4aa was not observed during the whole screening
process.
Table 1. Hydrophosphination of Azobenzene 1a with Diphenylphosphine Oxide 2a
under Various Conditionsa
Entry Oxidant (equiv) Additive (equiv) Solvent
1
T (oC) Time (h) Yield of 3aab
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20
20
20
20
6
0
K2S2O8 (3)
TBHP (3)
AgOAc (3)
Mn(OAc)3 (3)
DTBP (3)
DTBP (3)
DTBP (3)
DTBP (3)
/
/
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
110
110
110
110
110
110
110
110
110
110
21%
0
2
3
/
/
0
4
/
5
/
76%
84%
88%
78%
96%
95%
6
K2CO3 (1.1)
Cs2CO3 (1.1)
Na2CO3 (1.1)
Cs2CO3 (1.1)
Cs2CO3 (1.1)
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6
8
9
6
6
10
/
0.5
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/
/
/
/
/
/
/
/
Cs2CO3 (1.1)
Cs2CO3 (1.1)
Cs2CO3 (1.1)
Cs2CO3 (1.1)
Cs2CO3 (1.1)
Cs2CO3 (1.1)
Cs2CO3 (0.2)
/
DCE
DMSO
PhCl
110
110
110
110
100
80
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
92%
27%
48%
66%
98%
86%
16%
0
DMF
CH3CN
CH3CN
CH3CN
CH3CN
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aReaction conditions: 1a (0.25 mmol), 2a (0.5 mmol), oxidant (equiv), additive (equiv),
solvent (2 mL), time, air. bIsolated yield.
Having found the optimal reaction conditions, the scope of this interesting reaction was
explored using various azobenzenes 1 with diphenylphosphine oxide (2a). Gratifyingly, the
reaction was tolerant toward a variety of substituted azobenzenes and showed good
compatibility with a wide range of functional groups (Scheme 3). Unexpectedly, when
azobenzene 1b having 2-methyl group on the phenyl ring reacted with 2a, the desired
product 3ba was isolated in 21% yield. Meanwhile, diphenylphosphinic amide 4ba was
obtained in 37% yield, which may be attributed to the hydrolysis of 3ba. 3- and
4-methyl-substituted azobenzenes were well transformed to the corresponding products in
72% and 85% yields, respectively (3ca, 3da). As for 4-methoxy azobenzene 1ea, only 4ea
was afforded in 51% yield, and no desired product 3ea was observed. Azobenzenes
possessing halogen moieties on the para and meta positions furnished the
hydrophosphinated products in 44-88% yields (3fa, 3ga, 3ha, 3ia, 3ja). Substrates with
electron-withdrawing groups such as –OCF3, -COOEt on the aromatic ring underwent
hydrophosphination to give the corresponding products in good yields (3ka, 3la).
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Surprisingly, 2,4-disubstituted azobenzene 1ma only furnished diphenylphosphinic amide
4ma in 26% yield for 5 h. Overall, azobenzenes with electron-donating and
electron-withdrawing groups worked well with diphenylphosphine oxide. When
nonaromatic azo compound reacted with diphenylphosphine oxide, no desired product was
formed (3na).
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Scheme 3. Hydrophosphination of Substituted Azoarenes with Diphenylphosphine
Oxidea
aReaction conditions: 1 (0.25 mmol), 2a (0.5 mmol), Cs2CO3 (1.1 equiv) and CH3CN
(2 mL) at 100 oC for indicated time; Isolated yields. bDiisopropyl
o
diazene-1,2-dicarboxylate was tested instead of azoarenes; Run twice at 40 C and
60 oC, respectively.
Next, the reactions of variously substituted phenylphosphine oxides with 1a were examined
and the results are listed in Scheme 4. Both electron-donating and electron-withdrawing
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substituents on the aryl groups were well tolerated in this reaction (3ab-3ag). Among them,
the o-methyl substituted substrate 2b afforded a relatively lower yield of 38% probably due
to steric hindrance (3ab). Delightedly, di-2-naphthylphosphine oxide could also deliver the
corresponding product 3ah with a good yield of 53%. Moreover, heterocyclic phosphine
oxide compound was also well tolerated, affording the desired product 3ai in 64% yield.
Subsequently, phosphine oxides with two different substituents were employed. The
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unsymmetric
phosphine
oxides,
such
as
phenyl(p-tolyl)phosphine
oxide,
(4-methoxyphenyl)(phenyl)phosphine oxide worked well to deliver the corresponding
products in excellent yields (3ak, 3al). Unfortunately, ethyl phenylphosphinate was less
effective in the reaction (3aj). When dialkyl phosphites like diethyl phosphonate and
dimethyl phosphonate were tested, no desired product was obtained (3am, 3an). Notably,
no diphenylphosphinic amides were observed when broadening the scope of substituted
phenylphosphine oxides.
Scheme 4. Reaction of P(O)-H Compounds with Azobenzenea
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aReaction conditions: 1 (0.25 mmol), 2a (0.5 mmol), Cs2CO3 (1.1 equiv) and CH3CN (2 mL)
at 100 oC for indicated time; Isolated yields.
To test whether the reaction was amenable to scale-up (Scheme 5), we attempted a reaction
using 5 mmol of azobenzene (1a) and 10 mmol of diphenylphosphine oxide (2a).
Gratifyingly, 1a was converted into corresponding product 3aa in 91% yield.
Scheme 5. Synthesis of 3aa on Gram Scale
To establish a possible mechanism of the Cs2CO3-promoted hydrophosphination reaction,
some control experiments were carried out. First of all, to confirm whether the reaction
process was performed via a radical way, 1a and 2a were subjected to the standard
conditions using TEMPO and AIBN as radical scavenger, respectively (Scheme 6, eq 1). To
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our surprise, the yield of 3aa was not largely affected by the addition of these
radical-trapping reagents. These results indicate that this transformation via radical process
is excluded. Then the hydrophosphinated products 3aa was found to be intact under strong
base conditions using Cs2CO3, KOH, tBuOK respectively (Scheme 6, eq 2), however 3ba
was converted into diphenylphosphinic amide 4ba in 63% yield under base condition
(Scheme 6, eq 3).12 These results confirm that the formation of diphenylphosphinic amides
in some substrates was through the corresponding hydrophosphinated products as the
intermediates, and it depends on the stability of the hydrophosphinated products under base
condition.
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Scheme 6. Investigation of the Reaction Mechanism
Based on the above results and literature reports,10,13 it is reasonable to propose that the
hydrophosphination of aromatic azo compounds with diarylphosphine oxides proceeds via a
polar reaction mechanism as shown in Scheme 7. First, diphenylphosphine oxide can be
deprotonated to generate A under basic condition, then the N=N double bond is attacked by
A to form intermediate B. Finally this intermediate B abstracts H+ from 2a leading to the
final product 3aa and regenerating A. It should be noted that some diphenylphosphinic
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amides were obtained via the hydrolysis process of hydrophosphinated products observed in
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some substrates.
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Scheme 7. Plausible Mechanism
In summary, we have disclosed a convenient and practical method for the construction of
N-N-P unit. This newly developed protocol features short reaction time, good functional
group tolerance, and a plausible mechanism is proposed. Considering the valuable structure
of the products, this concise method to construct N-P bond may have potential applications
in the synthesis of related natural compounds and pharmaceuticals.
EXPERIMENTAL SECTION
General Information. 1H NMR , 13C NMR, 19F NMR and 31P NMR spectra were recorded
at 400 MHz , 100 MHz, 376 MHz and 162 MHz respectively using tetramethylsilane as an
internal reference. Chemical shifts (δ) and coupling constants (J) were expressed in parts
per million and hertz, respectively. Melting points were uncorrected. High-resolution mass
spectrometry (HRMS) was performed on an ESI-TOF spectrometer. Chemicals were
commercially available and used without purification. Aromatic azo compound substrates
were prepared according to the literature procedure.14 Substituted phenylphosphine oxides
were synthesized according to the reported procedure.15 Chromatography: Column
chromatography was performed with silica gel (200-300 mesh ASTM).
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General Experimental Procedures and Characterizations.
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Azobenzene (0.25 mmol), diphenylphosphine oxide (0.5 mmol, 2 equiv), Cs2CO3 (1.1
equiv), dry CH3CN (2 mL) and a stir bar were added to a sealed tube. After being stirred at
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100 C for indicated time, the mixture was evaporated under vacuum. The corresponding
products were isolated by silica gel column chromatography with a dichloromethane/ethyl
acetate mixture (100:4) as eluent.
N,N',P,P-tetraphenylphosphinic hydrazide (3aa). White solid. mp: 217-219 oC. Yield: 98%
(94 mg). 1H NMR (CDCl3, 400 MHz): δ 7.82 (dd, J1 = 7.6 Hz, J2 = 12.0 Hz, 4H), 7.48-7.34
(m, 8H), 7.16 (t, J = 7.6 Hz, 2H), 7.07 (t, J = 7.6 Hz, 2H), 6.98 (t, J = 7.6 Hz, 1H), 6.73 (d, J
= 8.4 Hz, 2H), 5.92 (s, 1H), 5.30 (s, 1H). 13C NMR (DMSO-d6, 100 Hz): δ 147.1 (d, JC-P
=
1.2 Hz), 143.8 (d, JC-P = 12.0 Hz), 133.4 (d, JC-P = 117.7 Hz), 131.9 (d, JC-P = 8.5 Hz), 128.5
31
(d, JC-P = 11.6 Hz), 123.3, 120.9 (d, JC-P = 2.5 Hz)，119.0, 113.0. P NMR (CDCl3, 162
MHz): δ 30.87. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H22N2OP 385.1470; Found
385.1465.
P,P-diphenyl-N,N'-di-o-tolylphosphinic hydrazide (3ba). Colorless oil. Yield: 21% (22 mg).
1H NMR (CDCl3, 400 MHz): δ 7.88-7.82 (m, 4H), 7.47 (t, J = 7.6 Hz, 2H), 7.41-7.35 (m,
4H), 7.29 (d, J = 7.6 Hz, 2H), 7.09-7.04 (m, 2H), 7.00 (t, J = 4.8 Hz, 2H), 6.88 (d, J = 7.2
Hz, 1H), 6.68 (t, J = 7.2 Hz, 1H), 5.90 (s, 1H), 2,47 (s, 3H), 1.93 (s, 3H). 13C NMR (CDCl3,
100 Hz): δ 143.8 (d, JC-P = 5.3 Hz), 141.1 (d, JC-P = 5.9 Hz), 135.4 (d, JC-P = 3.6 Hz), 132.3
(d, JC-P = 9.3 Hz), 131.9 (d, JC-P = 2.7 Hz), 130.5 (d, JC-P = 121.5 Hz), 128.5, 128.2 (d, JC-P
= 12.7 Hz), 127.0, 126.8 (d, JC-P = 2.1 Hz), 126.4, 126.3, 122.2, 120.2, 114.0, 19.3, 16.9. 31P
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NMR (CDCl3, 162 MHz): δ 30.43. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C26H26N2OP
413.1783; Found 413.1790.
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P,P-diphenyl-N-(o-tolyl)phosphinic amide (4ba).16 Pale white solid. mp: 130-132 oC. Yield:
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37% (29 mg). H NMR (DMSO-d6, 400 MHz): δ 7.85 (dd, J1 = 6.8 Hz, J2 = 11.6 Hz, 4H),
7.55-7.44 (m, 6H), 7.42 (s, 1H), 7.18 (d, J = 7.6 Hz, 1H), 7.12 (d, J = 7.2 Hz, 1H), 6.89 (t, J
= 7.2 Hz, 1H), 6.81 (t, J = 7.2 Hz, 1H), 2.39 (s, 3H). 13C NMR (DMSO-d6, 100 Hz): δ 139.4,
133.3 (d, JC-P = 127.3 Hz), 131.7 (d, JC-P = 9.4 Hz), 131.6 (d, JC-P = 2.4 Hz), 130.4, 129.6 (d,
31
JC-P = 8.5 Hz), 128.5 (d, JC-P = 12.2 Hz), 126.0, 122.4, 121.4 (d, JC-P = 4.8 Hz), 18.1. P
NMR (CDCl3, 162 MHz): δ 16.18. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H19NOP
308.1204; Found 308.1201.
o
P,P-diphenyl-N,N'-di-m-tolylphosphinic hydrazide (3ca). White solid. mp: 210-212 C.
Yield: 72% (74 mg). 1H NMR (CDCl3, 400 MHz): δ 7.82 (dd, J1 = 7.6 Hz, J2 = 12.4 Hz, 4H),
7.45 (t, J = 6.8 Hz, 2H), 7.39-7.33 (m, 4H), 7.22 (s, 1H), 7.13 (d, J = 8.0 Hz, 1H), 7.02 (t, J
= 7.6 Hz, 1H), 6.95 (t, J = 8.0 Hz, 1H), 6.78 (d, J = 7.6 Hz, 1H), 6.56 (t, J = 7.6 Hz, 2H),
6.49 (s, 1H), 5.95 (s, 1H), 2.19 (s, 3H), 2.16 (s, 3H). 13C NMR (CDCl3, 100 Hz): δ 146.2 (d,
JC-P = 3.4 Hz), 143.9 (d, JC-P = 9.2 Hz), 138.6 (d, JC-P = 8.1 Hz), 132.2 (d, JC-P = 9.6 Hz),
131.9 (d, JC-P = 2.7 Hz), 130.9 (d, JC-P = 128.4 Hz), 128.6 (d, JC-P = 15.4 Hz), 128.3 (d, JC-P
= 12.7 Hz), 125.1, 122.2 (d, JC-P = 2.5 Hz), 121.4, 118.5 (d, JC-P = 2.7 Hz), 114.2, 110.8,
21.5, 21.4. 31P NMR (CDCl3, 162 MHz): δ 30.68. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd
for C26H25N2NaOP 435.1602; Found 435.1625.
o
P,P-diphenyl-N,N'-di-p-tolylphosphinic hydrazide (3da). White solid. mp: 219-221 C.
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Yield: 85% (88 mg). H NMR (DMSO-d6, 400 MHz): δ 8.25 (d, J = 4.0 Hz, 1H), 7.82 (dd,
J1 = 7.2 Hz, J2 = 12.0 Hz, 4H), 7.49-7.40 (m, 6H), 7.33-7.27 (m, 2H), 6.91 (d, J = 8.4 Hz,
2H), 6.82 (d, J = 8.0 Hz, 2H), 6.74 (d, J = 8.4 Hz, 2H), 2.10 (s, 3H), 2.07 (s, 3H). 13C NMR
(CDCl3, 100 Hz): δ 142.7, 132.9, 132.1, 129.7 (d, JC-P = 23.0 Hz), 128.7 (d, JC-P = 2.0 Hz),
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124.9 (d, JC-P = 83.2 Hz), 120.7 (d, JC-P = 5.3 Hz), 116.7, 20.7, 20.6. P NMR (DMSO-d6,
162 MHz): δ 17.76. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C26H26N2OP 413.1783;
Found 413.1785.
N-(4-methoxyphenyl)-P,P-diphenylphosphinic amide (4ea).16 White solid. mp: 146-148 oC.
Yield: 51% (41 mg). 1H NMR (DMSO-d6, 400 MHz): δ 7.99 (d, J = 11.2 Hz, 1H), 7.82-7.76
(m, 4H), 7.58-7.47 (m, 6H), 7.01 (d, J = 9.2 Hz, 2H), 6.71 (d, J = 9.2 Hz, 2H), 3.62 (s, 3H).
13C NMR (DMSO-d6, 100 Hz): δ 153.7, 134.3 (d, JC-P = 112.3 Hz), 132.5, 131.6 (d, JC-P
=
9.9 Hz), 128.5 (d, JC-P = 12.4 Hz), 119.8 (d, JC-P = 6.7 Hz), 114.1, 55.0. 31P NMR
(DMSO-d6, 162 MHz): δ 16.27. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H19NO2P
324.1153; Found 324.1160.
N,N'-bis(4-fluorophenyl)-P,P-diphenylphosphinic hydrazide (3fa). Yellow solid. mp:
o
1
199-201 C. Yield: 44% (46 mg). H NMR (DMSO-d6, 400 MHz): δ 8.43 (d, J = 3.2 Hz,
1H), 7.84 (dd, J1 = 7.2 Hz, J2 = 12.0 Hz, 4H), 7.54-7.42 (m, 8H), 7.01 (t, J = 8.8 Hz, 2H),
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6.88-6.83 (m, 4H). C NMR (DMSO-d6, 100 Hz): δ 158.6 (d, JC-F = 257.5 Hz), 156.2 (d,
JC-F = 250.9 Hz), 143.2 (d, JC-P = 1.8 Hz), 139.6 (dd, JC-F = 11.2 Hz, JC-P = 2.5 Hz), 131.9 (d,
JC-P = 8.7 Hz), 131.3 (d, JC-P = 124.7 Hz), 131.1 (d, JC-P = 9.5 Hz), 128.7 (d, JC-P = 12.4 Hz),
128.4 (m), 124.1 (dd, JC-F = 8.0 Hz, JC-P = 2.1 Hz), 115.2 (dd, JC-F = 22.6 Hz, JC-P = 9.5 Hz),
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114.6 (d, JC-P = 7.3 Hz). P NMR (DMSO-d6, 162 MHz): δ 28.14. F NMR (DMSO-d6,
376 MHz): δ -118.74, -125.31. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H20F2N2OP
421.1281; Found 421.1275.
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N,N'-bis(4-chlorophenyl)-P,P-diphenylphosphinic hydrazide (3ga). White solid. mp:
o
1
204-206 C. Yield: 85% (96 mg). H NMR (DMSO-d6, 400 MHz): δ 8.67 (d, J = 2.4 Hz,
1H), 7.85-7.75 (m, 4H), 7.56-7.78 (m, 8H), 7.23 (d, J = 8.8 Hz, 2H), 7.06 (d, J = 8.8 Hz,
2H), 6.75 (d, J = 8.8 Hz, 2H). 13C NMR (DMSO-d6, 100 Hz): δ 150.9, 147.9 (d, JC-P = 12.0
Hz), 137.1 (d, JC-P = 11.7 Hz), 133.7 (d, JC-P = 4.6 Hz), 132.8 (d, JC-P = 113.1 Hz), 127.8,
127.3 (d, JC-P = 1.8 Hz), 119.6. 31P NMR (DMSO-d6, 162 MHz): δ 34.03. HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C24H20Cl2N2OP 453.0690; Found 453.0689.
N,N'-bis(4-bromophenyl)-P,P-diphenylphosphinic hydrazide (3ha). White solid. mp:
o
1
203-205 C. Yield: 78% (106 mg). H NMR (DMSO-d6, 400 MHz): δ 8.67 (d, J = 2.8 Hz,
1H), 7.79 (br, 4H), 7.61-7.42 (m, 6H), 7.39 (d, J = 9.2 Hz, 2H), 7.23 (d, J = 8.8 Hz, 2H),
7.06 (d, J = 8.8 Hz, 2H), 6.75 (d, J = 8.8 Hz, 2H). 13C NMR (DMSO-d6, 100 Hz): δ 145.7 (d,
JC-P = 1.1 Hz), 142.6, 131.9 (d, JC-P = 3.4 Hz), 131.8, 131.7 (d, JC-P = 7.8 Hz), 131.3 (d, JC-P
= 9.9 Hz), 128.5 (d, JC-P = 4.5 Hz), 127.8 (d, JC-P = 112.4 Hz), 122.4 (d, JC-P = 26.2 Hz),
122.1 (d, JC-P = 2.4 Hz), 117.6, 114.6 (d, JC-P = 43.9 Hz). 31P NMR (DMSO-d6, 162 MHz): δ
29.31. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H20Br2N2OP 540.9680; Found
540.9675.
N,N'-bis(3-chlorophenyl)-P,P-diphenylphosphinic hydrazide (3ia). White solid. mp:
o
1
219-221 C. Yield: 88% (99 mg). H NMR (DMSO-d6, 400 MHz): δ 8.79 (d, J = 2.4 Hz,
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1H), 7.86-7.75 (m, 4H), 7.61-7.42 (m, 6H), 7.41 (d, J = 6.4 Hz, 2H), 7.34 (d, J = 9.2 Hz,
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1H), 7.21 (t, J = 8.0 Hz, 1H), 7.07-6.98 (m, 2H), 6.73-6.64 (m, 2H). C NMR (DMSO-d6,
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100 Hz): δ 148.3, 145.3 (d, JC-P = 12.1 Hz), 133.2 (d, JC-P = 24.3 Hz), 132.1 (d, JC-P = 25.4
Hz), 131.9, 131.1 (d, JC-P = 154.5 Hz), 128.9 (d, JC-P = 12.4 Hz), 128.1 (d, JC-P = 12.1 Hz),
123.1, 119.4 (d, JC-P = 2.5 Hz), 118.9, 118.5 (d, JC-P = 2.1 Hz), 112.0, 111.3. 31P NMR
(DMSO-d6, 162 MHz): δ 29.89. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C24H20Cl2N2OP 453.0690; Found 453.0692.
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N,N'-bis(3-bromophenyl)-P,P-diphenylphosphinic hydrazide (3ja). White solid. mp:
o
1
220-222 C. Yield: 62% (84 mg). H NMR (DMSO-d6, 400 MHz): δ 8.76 (d, J = 1.6 Hz,
1H), 7.85-7.74 (m, 4H), 7.63-7.35 (m, 8H), 7.17-7.11 (m, 2H), 6.98 (t, J = 8.0 Hz, 1H), 6.85
(s, 1H), 6.78 (d, J = 8.0 Hz, 1H), 6.72 (d, J = 8.0 Hz, 1H). 13C NMR (DMSO-d6, 100 Hz): δ
148.4, 145.4 (d, JC-P = 12.1 Hz), 132.2 (d, JC-P = 26.5 Hz), 131.8 (d, JC-P = 3.3 Hz), 131.7 (d,
JC-P = 2.6 Hz), 130.7, 129.7 (d, JC-P = 166.6 Hz), 128.8, 128.1 (d, JC-P = 12.7 Hz), 126.0,
122.3 (d, JC-P = 2.3 Hz), 121.9, 121.6 (d, JC-P = 15.6 Hz), 118.9 (d, JC-P = 2.0 Hz), 114.9,
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111.6. P NMR (DMSO-d6, 162 MHz): δ 29.85. HRMS (ESI-TOF) m/z: [M + H]+ Calcd
for C24H20Br2N2OP 540.9680; Found 540.9680.
Diethyl 4,4'-(1-(diphenylphosphoryl)hydrazine-1,2-diyl)dibenzoate (3ka). White solid. mp:
234-236 oC. Yield: 92% (122 mg). 1H NMR (DMSO-d6, 400 MHz): δ 9.29 (s, 1H), 7.87 (dd,
J1 = 8.4 Hz, J2 = 12.4 Hz, 2H), 7.80-7.70 (m, 6H), 7.65-7.59 (m, 4H), 7.46 (d, J = 9.2 Hz,
2H), 7.41-7.33 (m, 2H), 6.71 (d, J = 8.8 Hz, 2H), 4.24-4.15 (m, 4H), 1.23 (t, J = 6.8 Hz, 6H).
13C NMR (DMSO-d6, 100 Hz): δ 165.2 (d, JC-P = 28.1 Hz), 150.9, 148.6 (d, JC-P = 12.2 Hz),
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132.4 (d, JC-P = 2.9 Hz), 131.9 (d, JC-P = 10.1 Hz), 131.8, 131.7 (d, JC-P = 6.5 Hz), 130.6,
130.3, 130.1 (d, JC-P = 5.2 Hz), 129.0 (d, JC-P = 5.0 Hz), 128.8 (d, JC-P = 5.2 Hz), 128.0 (d,
JC-P = 13.0 Hz), 127.1 (d, JC-P = 162.5 Hz), 117.8 (d, JC-P = 1.9 Hz), 111.2, 60.3, 59.9, 14.2,
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14.1. P NMR (DMSO-d6, 162 MHz): δ 31.06. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd
for C30H29N2NaO5P 551.1712; Found 551.1707.
P,P-diphenyl-N,N'-bis(4-(trifluoromethoxy)phenyl)phosphinic hydrazide (3la). Yellow
solid. mp: 174-176 oC. Yield: 72% (99 mg). 1H NMR (DMSO-d6, 400 MHz): δ 8.79 (d, J =
2.0 Hz, 1H), 7.87-7.75 (m, 4H), 7.59-7.48 (m, 6H), 7.47-7.37 (m, 2H), 7.22 (d, J = 8.8 Hz,
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2H), 7.02 (d, J = 8.4 Hz, 2H), 6.78 (d, J = 9.2 Hz, 2H). C NMR (DMSO-d6, 100 Hz): δ
145.9, 143.8 (d, JC-P = 1.6 Hz), 142.8 (d, JC-P = 12.1 Hz), 140.7 (d, JC-P = 1.4 Hz), 131.8 (d,
JC-P = 9.7 Hz), 131.6 (d, JC-P = 116.2 Hz), 128.7 (d, JC-P = 14.2 Hz), 128.0 (d, JC-F = 11.4
Hz), 124.9, 120.3 (q, JC-F = 253.0 Hz), 120.1 (q, JC-F = 254.2 Hz), 118.7 (d, JC-P = 16.9 Hz)
113.4. 31P NMR (DMSO-d6, 162 MHz): δ 29.61. 19F NMR (DMSO-d6, 376 MHz): δ -57.08,
-57.29. HRMS (ESI-TOF) m/z: [M - H]- Calcd for C26H18F6N2O3P 551.0959; Found
551.0953.
N-(2,4-dimethylphenyl)-P,P-diphenylphosphinic amide (4ma). Orange solid. mp: 144-146
oC. Yield: 26% (21 mg). H NMR (DMSO-d6, 400 MHz): δ 7.84 (dd, J1 = 6.4 Hz, J2 = 11.6
1
Hz, 4H), 7.51-7.44 (m, 6H), 7.34 (d, J = 8.8 Hz, 1H), 7.09 (d, J = 8.0 Hz, 1H), 6.93 (s, 1H),
13
6.69 (d, J = 8.0 Hz, 1H) 2.35 (s, 3H), 2.12 (s, 3H). C NMR (DMSO-d6, 100 Hz): δ 136.6,
133.4 (d, JC-P = 127.4 Hz), 131.8 (d, JC-P = 9.3 Hz), 131.5 (d, JC-P = 2.5 Hz), 131.3, 131.0,
129.8 (d, JC-P = 8.4 Hz), 128.5 (d, JC-P = 12.2 Hz), 126.4, 121.7 (d, JC-P = 4.5 Hz), 20.2, 18.0.
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31P NMR (DMSO-d6, 162 MHz): δ 16.06. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
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C20H20NNaOP 344.1180; Found 344.1177.
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N,N'-diphenyl-P,P-di-o-tolylphosphinic hydrazide (3ab). White solid. mp: 195-197 C.
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Yield: 38% (39 mg). H NMR (DMSO-d6, 400 MHz): δ 8.39 (s, 1H), 7.70-7.43 (m, 6H),
7.29 (br, 3H), 7.19 (t, J = 7.6 Hz, 2H), 7.07-6.93 (m, 4H), 6.66 (d, J = 8.0 Hz, 2H), 6.56 (t, J
= 7.2 Hz, 1H), 2.37 (s, 3H), 2.23 (s, 3H). 13C NMR (DMSO-d6, 100 Hz): δ 146.7 (d, JC-P
=
1.3 Hz), 144.8 (d, JC-P = 11.8 Hz), 141.9, 132.5 (d, JC-P = 139.2 Hz), 131.1 (d, JC-P = 11.7
Hz), 128.4 (d, JC-P = 18.4 Hz), 125.4 (d, JC-P = 16.8 Hz), 124.7, 122.5, 119.2 (d, JC-P = 1.6
31
Hz), 118.8, 112.5, 21.4, 20.9. P NMR (DMSO-d6, 162 MHz): δ 34.84. HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C26H26N2OP 413.1783; Found 413.1789.
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N,N'-diphenyl-P,P-di-m-tolylphosphinic hydrazide (3ac). White solid. mp: 205-207 C.
Yield: 51% (53 mg). 1H NMR (DMSO-d6, 400 MHz): δ 8.44 (d, J = 3.6 Hz, 1H), 7.71-7.56
(m, 4H), 7.40 (d, J = 8.8 Hz, 2H), 7.30 (br, 4H), 7.14 (t, J = 7.6 Hz, 2H), 7.01 (t, J = 8.8 Hz,
2H), 6.88 (t, J = 7.6 Hz, 1H), 6.78 (d, J = 8.8 Hz, 2H), 6.60 (t, J = 7.6 Hz, 1H), 2.27 (s, 6H).
13C NMR (DMSO-d6, 100 Hz): δ 147.1 (d, JC-P = 0.9 Hz), 143.9 (d, JC-P = 11.9 Hz), 137.3,
132.2 (d, JC-P = 4.9 Hz), 131.2 (d, JC-P = 120.9 Hz), 129.0 (d, JC-P = 9.3 Hz), 128.4 (d, JC-P
=
8.6 Hz), 123.1, 120.7 (d, JC-P = 2.5 Hz), 118.9, 112.9, 20.9. 31P NMR (DMSO-d6, 162 MHz):
δ 28.78. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C26H25N2NaOP 435.1602; Found
435.1595.
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N,N'-diphenyl-P,P-di-p-tolylphosphinic hydrazide (3ad). White solid. mp: 215-217 C.
Yield: 92% (94 mg). 1H NMR (DMSO-d6, 400 MHz): δ 8.43 (d, J = 3.6 Hz, 1H), 7.68 (t, J =
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8.0 Hz, 4H), 7.39 (d, J = 8.0 Hz, 2H), 7.23 (br, 4H), 7.12 (t, J = 7.6 Hz, 2H), 7.01 (t, J = 7.6
Hz, 2H), 6.88 (t, J = 7.6 Hz, 1H), 6.80 (d, J = 7.6 Hz, 2H), 6.60 (t, J = 7.2 Hz, 1H), 2.28 (s,
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6H). C NMR (DMSO-d6, 100 Hz): δ 147.2 (d, JC-P = 1.1 Hz), 143.9 (d, JC-P = 11.8 Hz),
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131.8 (d, JC-P = 9.1 Hz), 128.5 (d, JC-P =17.0 Hz), 123.1, 121.9 (d, JC-P = 127.4 Hz), 120.8,
118.8, 112.9, 20.9. 31P NMR (DMSO-d6, 162 MHz): δ 29.01. HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C26H26N2OP 413.1783; Found 413.1783.
P,P-bis(4-methoxyphenyl)-N,N'-diphenylphosphinic hydrazide (3ae). White solid. mp:
o
1
202-204 C. Yield: 97% (107 mg). H NMR (DMSO-d6, 400 MHz): δ 8.41 (d, J = 2.8 Hz,
1H), 7.70 (t, J = 8.8 Hz, 4H), 7.38 (d, J = 8.4 Hz, 2H), 7.12 (t, J = 7.6 Hz, 2H), 7.03-6.96 (m,
6H), 6.87 (t, J = 7.2 Hz, 1H), 6.78 (d, J = 7.6 Hz, 2H), 6.59 (t, J = 7.6 Hz, 1H), 3.75 (s, 6H).
13C NMR (DMSO-d6, 100 Hz): δ 161.7 (d, JC-P = 1.7 Hz), 147.3 (d, JC-P = 1.0 Hz), 144.1 (d,
JC-P = 11.9 Hz), 133.7 (d, JC-P =10.7 Hz), 128.4 (d, JC-P = 20.2 Hz), 123.9 (d, JC-P = 2.1 Hz),
123.2 (d, JC-P = 132.2 Hz), 122.6, 120.6 (d, JC-P = 2.5 Hz), 118.7, 113.4 (d, JC-P = 34.0 Hz),
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112.8, 55.2. P NMR (DMSO-d6, 162 MHz): δ 28.92. HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C26H26N2O3P 445.1681; Found 445.1686.
P,P-bis(4-fluorophenyl)-N,N'-diphenylphosphinic hydrazide (3af). White solid. mp:
o
1
203-205 C. Yield: 28% (30 mg). H NMR (DMSO-d6, 400 MHz): δ 8.51 (d, J = 3.2 Hz,
1H), 7.88 (br, 4H), 7.40 (d, J = 8.0 Hz, 2H), 7.30 (br, 4H), 7.16 (t, J = 7.6 Hz, 2H), 7.03 (t, J
= 8.0 Hz, 2H), 6.92 (t, J = 7.2 Hz, 1H), 6.79 (d, J = 7.6 Hz, 2H), 6.62 (t, J = 7.2 Hz, 1H).
13C NMR (DMSO-d6, 100 Hz): δ 164.2 (d, JC-F = 254.6 Hz), 162.9, 146.9 (d, JC-P = 1.3 Hz),
143.4 (d, JC-P = 12.1 Hz), 134.8 (d, JC-P = 9.5 Hz), 134.7, 128.6 (d, JC-P = 7.9 Hz), 123.5,
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120.9, 120.1 (d, JC-P = 184.5 Hz), 115.6 (m), 112.9. 31P NMR (DMSO-d6, 162 MHz): δ
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26.65. F NMR (DMSO-d6, 376 MHz): δ -107.29, -107.64. HRMS (ESI-TOF) m/z: [M +
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H]+ Calcd for C24H20F2N2OP 421.1281; Found 421.1277.
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P,P-bis(4-chlorophenyl)-N,N'-diphenylphosphinic hydrazide (3ag). White solid. mp:
o
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202-204 C. Yield: 87% (98 mg). H NMR (DMSO-d6, 400 MHz): δ 8.48 (d, J = 3.6 Hz,
1H), 7.85-7.79 (m, 4H), 7.53-7.39 (m, 6H), 7.13 (t, J = 7.6 Hz, 2H), 7.01 (t, J = 8.0 Hz, 2H),
6.89 (t, J = 7.6 Hz, 1H), 6.79 (d, J = 8.0 Hz, 2H), 6.60 (t, J = 7.2 Hz, 1H). 13C NMR
(DMSO-d6, 100 Hz): δ 147.1 (d, JC-P = 1.3 Hz), 143.7 (d, JC-P = 12.0 Hz), 133.4, 132.6 (d,
JC-P = 139.4 Hz), 131.8, 131.2 (d, JC-P =9.9 Hz), 128.7 (d, JC-P = 36.0 Hz), 123.2, 120.9 (d,
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JC-P = 2.6 Hz), 118.9, 112.9. P NMR (DMSO-d6, 162 MHz): δ 28.34. HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C24H20Cl2N2OP 453.0690; Found 453.0686.
P,P-di(naphthalen-2-yl)-N,N'-diphenylphosphinic hydrazide (3ah). White solid. mp:
211-213 oC. Yield: 53% (64 mg). 1H NMR (DMSO-d6, 400 MHz): δ 8.64 (d, J = 3.6 Hz, 1H),
8.56 (br, 2H), 8.02 (d, J = 7.6 Hz, 2H), 7.91 (d, J = 8.0 Hz, 6H), 7.63-7.56 (m, 4H), 7.50 (d,
J = 8.4 Hz, 2H), 7.13 (t, J = 7.6 Hz, 2H), 7.01 (t, J = 8.4 Hz, 2H), 6.90-6.85 (m, 3H), 6.59 (t,
J = 7.2 Hz, 1H). 13C NMR (DMSO-d6, 100 Hz): δ 147.1, 143.7 (d, JC-P = 11.9 Hz), 134.0 (d,
JC-P = 3.9 Hz), 128.8, 128.6 (d, JC-P = 8.6 Hz), 127.5 (d, JC-P = 137.3 Hz), 126.9, 123.4,
121.0, 119.0, 113.1. 31P NMR (DMSO-d6, 162 MHz): δ 28.03. HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C32H26N2OP 485.1783; Found 485.1780.
N,N'-diphenyl-P,P-di(thiophen-2-yl)phosphinic hydrazide (3ai). White solid. mp: 185-187
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oC. Yield: 64% (63 mg). H NMR (DMSO-d6, 400 MHz): δ 8.45 (d, J = 0.8 Hz, 1H), 7.98
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(br, 2H), 7.66 (q, J = 4.0 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H), 7.21 (t, J = 7.6 Hz, 4H),
7.07-6.98 (m, 3H), 6.80 (d, J = 8.6 Hz, 2H), 6.65 (t, J = 7.2 Hz, 1H). 13C NMR (DMSO-d6,
100 Hz): δ 146.8 (d, JC-P = 3.8 Hz), 142.8 (d, JC-P = 12.5 Hz), 128.6 (d, JC-P = 7.7 Hz), 123.9,
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121.3, 119.4 (d, JC-P = 180.4 Hz), 113.4. P NMR (DMSO-d6, 162 MHz): δ 15.00. HRMS
(ESI-TOF) m/z: [M + Na]+ Calcd for C20H17N2NaOPS2 419.0418; Found 419.0415.
o
N,N',P-triphenyl-P-(p-tolyl)phosphinic hydrazide (3ak). White solid. mp: 200-202 C.
Yield: 90% (89 mg). 1H NMR (DMSO-d6, 400 MHz): δ 8.46 (d, J = 3.6 Hz, 1H), 7.79 (t, J =
8.0 Hz, 2H), 7.71 (t, J = 8.0 Hz, 2H), 7.46-7.38 (m, 5H), 7.25 (br, 2H), 7.13 (t, J = 7.6 Hz,
2H), 7.01 (t, J = 8.4 Hz, 2H), 6.88 (t, J = 7.2 Hz, 1H), 6.79 (d, J = 8.0 Hz, 2H), 6.60 (t, J =
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7.2 Hz, 1H), 2.29 (s, 3H). C NMR (DMSO-d6, 100 Hz): δ 147.2 (d, JC-P = 1.1 Hz), 143.8
(d, JC-P = 11.9 Hz), 131.8 (m), 128.5 (d, JC-P = 14.3 Hz), 123.1, 120.8, 118.9, 112.9, 21.00.
31P NMR (DMSO-d6, 162 MHz): δ 28.75. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C25H24N2OP 399.1626; Found 399.1634.
P-(4-methoxyphenyl)-N,N',P-triphenylphosphinic hydrazide (3al). White solid. mp:
o
1
176-178 C. Yield: 93% (96 mg). H NMR (DMSO-d6, 400 MHz): δ 8.45 (d, J = 3.2 Hz,
1H), 7.81-7.71 (m, 5H), 7.39 (d, J = 8.4 Hz, 4H), 7.16-7.10 (m, 2H), 7.01 (t, J = 8.4 Hz, 4H),
6.88 (t, J = 7.2 Hz, 1H), 6.79 (d, J = 7.6 Hz, 2H), 6.60 (t, J = 7.2 Hz, 1H), 3.75 (s, 3H). 13C
NMR (DMSO-d6, 100 Hz): δ 162.3, 147.2 (d, JC-P = 0.9 Hz), 133.8 (d, JC-P = 29.8 Hz), 131.5
(d, JC-P = 50.0 Hz), 128.4 (d, JC-P = 15.9 Hz), 123.1, 121.9 (d, JC-P = 129.5 Hz), 120.7, 118.8,
114.6, 112.9, 55.2. 31P NMR (DMSO-d6, 162 MHz): δ 29.51. HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C25H24N2O2P 415.1575; Found 415.1565.
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This Supporting Information is available free of charge on the ACS Publications websites at
http://pubs.acs.org. Copies of 1H, 13C, 31P, and 19F NMR spectra for products (PDF).
Corresponding Authors
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*E-mail: wanglimin@ecust.edu.cn.
*E-mail: wsy1986wsy@126.com.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This research was financially supported by the National Nature Science Foundation of
China (21272069, 20672035) and the Fundamental Research Funds for the Central
Universities and Key Laboratory of Organofluorine Chemistry, Shanghai Institute of
Organic Chemistry, Chinese Academy of Sciences.
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