1,8-Diazabicyclo[5.4.0]undec-7-ene-mediated formation of N-sulfinyl imines

Article abstract of DOI:10.1177/1747519819884146

A facile and efficient method was developed for the preparation of a variety of aryl, heteroaryl, and alkyl N-sulfinyl imines using 1,8-diazabicyclo[5.4.0]undec-7-ene. In addition to tert-butanesulfinamide, the condensation is also effective with p-toluenesulfinamide. The reaction was performed at room temperature and produces the corresponding N-sulfinyl imines in excellent yields in the absence of acids, metals, and additives. This methodology is also useful for the preparation of N-sulfinyl imines on gram scale. A one-pot synthesis was developed using aryl and heteroaryl alcohols with both tert-butanesulfinamide and p-toluenesulfinamide at room temperature, resulting in the corresponding N-sulfinyl imines with good yields.

Full text of DOI:10.1177/1747519819884146

884146CHL0010.1177/1747519819884146Journal of Chemical ResearchRamaiah et al.
research-article2019
Research Paper
Journal of Chemical Research
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1,8-Diazabicyclo[5.4.0]undec-7-ene-mediated
formation of N-sulfinyl imines
https://doi.org/10.1177/1747519819884146
DOI: 10.1177/1747519819884146
journals.sagepub.com/home/chl
Manjunatha M Ramaiah1, Priya Babu Shubha1
,
Pavan Kumar Prabhala2 and Nanjunda Swamy Shivananju3
Abstract
A facile and efficient method was developed for the preparation of a variety of aryl, heteroaryl, and alkyl N-sulfinyl imines
using 1,8-diazabicyclo[5.4.0]undec-7-ene. In addition to tert-butanesulfinamide, the condensation is also effective with p-
toluenesulfinamide. The reaction was performed at room temperature and produces the corresponding N-sulfinyl imines
in excellent yields in the absence of acids, metals, and additives. This methodology is also useful for the preparation of
N-sulfinyl imines on gram scale. A one-pot synthesis was developed using aryl and heteroaryl alcohols with both tert-
butanesulfinamide and p-toluenesulfinamide at room temperature, resulting in the corresponding N-sulfinyl imines with
good yields.
Keywords
condensation, 1,8-diazabicyclo[5.4.0]undec-7-ene, N-sulfinyl imines, one-pot synthesis, sulfinamide
Date received: 31 July 2019; accepted: 30 September 2019
and so on, to accomplish this conversion. These methods suf-
Introduction
fer from certain disadvantages like long reaction times, heat-
Imine bond formation by the condensation of carbonyl com-
ing, low yields, formation of by-products, and usage of large
pounds and primary amine groups is important in organic syn-
excess reagents. Nevertheless, several reagents can achieve
thesis due to the significance of imines in the fields of
this transformation; indeed, there is a scope for the develop-
chemistry and biology.1 Chiral sulfinamides function as amine
ment of mild and efficient methods to address the drawbacks
counterparts and have been employed as useful chiral auxilia-
of the existing methodologies.
ries in asymmetric synthesis.2–4 They represent key building
blocks for the synthesis of a number of biologically active
molecules, chiral amines,4–8 and aziridines9–12 and also are
1Synthetic Laboratory, Department of Studies in Chemistry, University
of Mysore, Mysore, India
pounds with industrial interest.13 There are several reports for
2Department of Chemistry, S.V.R.M. College, Acharya Nagarjuna
constituents of pharmaceuticals, agro-chemicals, and com-
the synthesis of aldimines, and these are mainly based on the
University, Guntur, India
3Department of Biotechnology, JSS Science and Technology University,
Mysore, India.
condensation of aldehydes with sulfinamides in the presence
of reagents containing metals. Earlier reports were focused on
the application of either activating or dehydrating agents such
as copper(II) sulfate,14 magnesium sulfate–pyridinium p-tol-
uenesulfonate,14 titanium(IV) alkoxides,14–16 cesium carbon-
Corresponding author:
Priya Babu Shubha, Synthetic Laboratory, Department of Studies in
Chemistry, University of Mysore, Manasagangotri, Mysore 570006, India.
ate,17 ytterbium(III) triflate,18 potassium hydrogen sulfate,19 Email: priyabs_chem@yahoo.com

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Journal of Chemical Research 00(0)
Table 1. Optimization of the reaction conditions.
Entry
Base (equiv.)
Solvent
Time (h)
Temp (°C)
Isolated yield (%)a
1
2
3
4
5
6
7
8
NMM (1.5)
DABCO (1.5)
DBU (1.5)
DBU (1.5)
DBU (1.5)
DBU (1.5)
DBU (1.5)
DBU (1.5)
DBU (1.5)
DBU (1.0)
DBU (2.0)
DBU (1.5)
DBU (1.5)
DBU (1.5)
THF
THF
THF
THF
THF
1,4-Dioxane
DME
DMF
Solvent free
DMF
0.5
0.5
0.5
1
2
2
2
2
2
2
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
50
npb
npb
35
62
85
72
75
87
npb
72
87
30
45
55
9
10
11
12
13
14
DMF
DMF
DMF
DMF
2
0.5
1
50
50
2
NMM: N-methylmorpholine;THF: tetrahydrofuran; DABCO: 1,4-diazabicyclo[2.2.2]octane; DBU: 1,8-diazabicyclo[5.4.0]undec-7-ene; DME:
dimethoxyethane; DMF: dimethyl formamide; RT: room temperature.
aIsolated yield after chromatographic purification.
bnp: No product formation was observed.
The bold values inTable 1, indicate the best condition among screened conditions this is to attract readers attention to find the best among screened
conditions.
1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) is a steri- solvents, time, stoichiometry, and temperature, and the
cally hindered amidine, which is used as a non-nucleo- results are summarized in Table 1. The results indicated
philic base in organic synthesis to achieve various that the solvents THF, 1,4-dioxane, dimethoxyethane
transformations.20 It is cheap, readily available, and easy (DME), and dimethyl formamide (DMF) were suitable for
to remove from reaction mixtures. To the best of our the reaction (Table 1, entries 5–8). It was established that
knowledge, methods for the synthesis of N-sulfinyl DMF was the best among the screened solvents. No prod-
imines using DBU have not been reported yet. Herein, uct formation was observed in the case of the solvent-free
we aimed to develop a simple, mild, highly efficient, reaction after 2h (Table 1, entry 9). In summary, this reac-
economic, and metal-free protocol for the formation of tion is best performed with 1 (1.0mmol) and 2 (1.5mmol)
sulfinyl imines from sulfinamides and aldehydes in the in the presence of DBU (1.5mmol) in DMF at room tem-
presence of DBU. This method offers various advan- perature (Table 1, entry 8). The scope of this condensation
tages such as high yields and simple work-up, is scala- is amenable not only for N-(tert-butylsulfinyl)imines but
ble, and employs mild reaction condition.
also for N-p-toluenesulfinyl imines. Alternatively, a one-
pot synthesis was carried out with alcohols and sulfina-
mides by employing manganese dioxide and DBU at room
temperature to obtain good product yields.
Results and discussion
We initially optimized the method by using benzaldehyde
With optimized reaction conditions in hand, the scope of
(1; Table 1) and (S)-tert-butanesulfinamide (2) as starting the reaction was subsequently examined with respect to
materials. In our preliminary experiments, benzaldehyde various aldehydes (Table 2). The parent benzaldehyde
(1) (1.0 equiv.) was subjected to reaction with (S)-tert- (Table 2, entry 1) was smoothly reacted with 2, and the cor-
butanesulfinamide (2) (1.5 equiv.) in the presence of dif- responding sulfinyl imine 3a was obtained in 87% yield.
ferent bases such as N-methylmorpholine (NMM), Condensation of an electron-donating benzaldehyde (Table
1,4-diazabicyclo[2.2.2]octane (DABCO), and 1,8-diaz- 2, entry 2) with 2 provided the sulfinyl imine in lower yield
abicyclo[5.4.0]undec-7-ene (DBU) in tetrahydrofuran when compared to an electron-withdrawing benzaldehyde
(THF) at room temperature to obtain the corresponding (Table 2, entry 3). The reaction was explored with substrates
sulfinyl imine. After 0.5h, there was no product formation bearing ortho, para, and meta substitutents (Table 2, entries
in case of NMM and DABCO, whereas formation of the 4–8) which were also converted into the corresponding
desired product 3a was observed with DBU (Table 1, sulfinyl imines in good to excellent yields. Simple and sub-
entries 1–3), which was analyzed by thin-layer chroma- stituted pyridine carboxaldehydes (Table 2, entries 9 and 10)
tography (TLC) and confirmed by 1H nuclear magnetic reacted efficiently with 2 to provide imines 3i and 3j in simi-
resonance (NMR). To determine the optimum reaction lar yields. The bicyclic quinoline-8-carbaldehyde (Table 2,
conditions, we further investigated the influence of entry 11) provided the corresponding imine 3k in 85% yield.

Ramaiah et al.
3
Table 2. Synthesis of N-(tert-butylsulfinyl)imines 3a–pa.
Entry
R
Time(h)
Product
Isolated yield (%)b
1
2
3
4
5
6
7
8
C6H5
2
8
3
4
4
2
8
7
2
2
5
3
5
5
6
6
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
87
81
92
83
87
92
90
80
94
96
85
91
90
88
91
83
4-MeOC6H4
4-NCC6H4
2-FC6H4
4-FC6H4
3-BrC6H4
2-EtOOCC6H4
4-tBuC6H4
3-Pyridyl
5-Br-2-MeO-4-Pyridyl
8-Quinolinyl
3-Furyl
Cyclopropyl
Cyclohexyl
tert-butyl
9
10
11
12
13
14
15
16
(E)-2-hexenyl
DBU: 1,8-diazabicyclo[5.4.0]undec-7-ene; DMF: dimethyl formamide; RT: room temperature.
aReaction conditions: aldehyde (1.0mmol) and 2 (1.5mmol) in DMF (1mL) in the presence of DBU (1.5mmol) at RT for 2–8h.
bIsolated yield after chromatographic purification.
Similarly, furan-3-carbaldehyde (Table 2, entry 12) corresponding racemic products, and the enantiomeric
gave the desired product 3l in high yield. On the other excess was determined as >99% in both the cases (The
hand, aliphatic secondary, tertiary, and unsaturated alde- enantioselectivity of 3a and 3b was determined as >99%
hydes (Table 2, entries 13–16) were converted into the by chiral HPLC. (See the Supporting Information for
corresponding imines 3m–p in high yields, thus demon- HPLC data)). Thus, the significance of this method is that
strating the potential of our synthetic methodology. Thus, there was no racemization observed upon condensation of
this methodology is applicable for the reactions of a vari- aldehydes with (S)-tert-butanesulfinamide.
ety of aliphatic, aryl, and heteroaryl aldehydes with (S)-
To illustrate the scalability of the standardized conditions,
tert-butanesulfinamide (2) in the presence of DBU, and a scale-up batch was performed by using 1 (5g, 47.17mmol)
the reactions were complete in 2–8h. After completion of and 2 (8.56g, 70.74mmol) in DMF (65mL) in the presence
the reaction, the mixture was subjected to a simple aque- of DBU (10.75g, 70.74mmol) at room temperature for 2h.
ous work-up. The residue was subjected to silica gel col- After chromatographic purification, the desired product 3a
umn chromatography, and the corresponding products was obtained in a comparable yield (8.4g, 85%). From this
3a–p were isolated. The chiral purities of sulfinyl imines experiment, it was confirmed that our method is applicable
3a and 3b were evaluated by comparison with the for the preparation of sulfinyl imines on gram scale also.

4
Journal of Chemical Research 00(0)
Table 3. Synthesis of N-p-toluenesulfinyl imines 4a–ja.
Entry
R
Time(h)
Product
Isolated yield (%)b
1
2
3
4
5
6
7
8
9
C6H5
3
10
3
6
3
7
5
5
5
4a
4b
4c
4d
4e
4f
4g
4h
4i
81
78
85
80
91
82
86
82
85
81
4-MeOC6H4
4-NCC6H4
4-tBuC6H4
3-BrC6H4
2-HOC6H4
3-Thienyl
3-Furyl
2-MeO-4-pyridyl
8-Quinolinyl
10
6
4j
DBU: 1,8-diazabicyclo[5.4.0]undec-7-ene; DMF: dimethyl formamide; RT: room temperature.
aReaction conditions: aldehyde (1.0mmol) and 2a (1.5mmol) in DMF (1mL) in the presence of DBU (1.5mmol) at RT for 3–10h.
bIsolated yield after chromatographic purification.
In addition to N-(tert-butylsulfinyl)imine (2), it was yields. Unfortunately, enolizable aliphatic aldehydes upon
observed that the condensation was also effective with (S)- condensation with (S)-p-toluenesulfinamide (2a) resulted in
p-toluenesulfinamide (2a), as introduced by Davis, which is the corresponding products which were unstable as sup-
another commonly used chiral auxiliary.8 Under the stand- ported by 1H NMR.
ardized conditions, it reacted with aldehydes to provide the
Subsequently, we conducted the one-pot synthesis of
corresponding imines 4a–k in high yields (Table 3). With N-sulfinyl imine21 using benzyl alcohol (Table 4, entry 1),
the optimized conditions in hand, the initial reaction was (S)-tert-butanesulfinamide 2, and manganese dioxide in the
performed with 1 and 2a in the presence of DBU at room presence of DBU in DMF at room temperature. As we antici-
temperature for 3h and 4a was obtained in 81% yield. The pated, after 3h, the formation of the corresponding product
reaction was amenable for both electron-donating (Table 3, 3a was observed by TLC; the reaction was continued, and
entry 2) and electron-withdrawing (Table 3, entry 3) aro- complete conversion was observed after 5h. The product
matic aldehydes. Notably, the reaction also tolerated for was isolated in 75% yield, and the structure was confirmed
substrates bearing para, meta, and ortho substituents (Table by 1H NMR. The reaction proceeds through in situ oxidation
3, entries 4–6), which were converted smoothly into the cor- of the alcohol to corresponding aldehyde in the presence of
responding N-sulfinyl imines 4d, 4e, and 4f in good yields. manganese dioxide, which upon subsequent condensation
Similarly, five-membered heterocyclic aldehydes (Table 3, with the sulfinamide affords the corresponding N-sulfinyl
entries 7 and 8) were condensed with 2a to provide 4g and imine. Electron-withdrawing and electron-donating aromatic
4h in 86% and 82% yields, respectively. 2-Methoxypyridine- alcohols (Table 4, entries 2 and 3) reacted with both the sulfi-
4-carbaldehyde (Table 3, entry 9) upon condensation with namides 2 and 2a to give the corresponding products 3b, 3c,
2a was also effective, giving the corresponding imine 4i in 4b, and 4c in good yields. Similarly, substrates bearing mono
good yield. A bicyclic aldehyde (Table 3, entry 10) also pro- ortho, para, and meta substituents (Table 4, entries 4–7) also
duced the corresponding product 4j in 81% yield. All the gave the corresponding imines. Simple and substituted pyri-
reactions were performed at room temperature, were com- dine alcohols (Table 4, entries 8 and 9) were converted into
pleted in 3–10h, and all the products were obtained in high aldehydes and reacted with 2 and 2a successfully to give the

Ramaiah et al.
5
Table 4. One-pot synthesis of N-sulfinyl iminesa.
provide N-sulfinyl imines at room temperature. The reac-
tions proceed under mild and homogeneous conditions with
clean reaction profiles and simple work-up. The method
was shown to be appropriate for a broad range of alde-
hydes, including sterically hindered, electron-rich, and
electron-deficient substrates. This methodology is also use-
ful for the preparation of N-sulfinyl imines on gram scale.
Remarkably, the one-pot reaction of aromatic and heter-
oaromatic alcohols with sulfinamides for the preparation of
the corresponding N-sulfinyl imines resulted in good yields.
Unfortunately, this one-pot protocol for the formation of
N-sulfinyl imines was unsuccessful with aliphatic
alcohols.
Entry
R
Time (h)
Product
Isolated
yield (%)b
1
2
3
C6H5
5
7
15
15
5
7
6
5
3a
4a
3b
4b
3c
4c
3e
3f
75
72
70
68
76
71
75
81
76
70
75
71
83
75
76
70
npc
4-MeOC6H4
4-NCC6H4
Experimental
4
5
4-FC6H4
3-BrC6H4
All reagents and solvents used in this work were obtained
from commercial sources and were used without further
purification. TLC was performed on Merck silica gel 60F254
(0.25-mm thickness) plates and visualized under UV light.
Column chromatography was performed using brand silica
gel of 100–200 mesh. Melting points were determined in
open capillary tubes using paraffin oil bath and are uncor-
rected. NMR data were collected for 1H at 400MHz and
for 13C at 100MHz on an Agilent NMR spectrometer.
Chemical shifts are reported in parts per million relative to
tetramethylsilane (TMS) as an internal standard (δ 0), and
the values are reported as follows: chemical shift, integra-
tion, multiplicity (s=singlet, d=doublet, t=triplet, q=quar-
tet, m=multiplet, br s=broad singlet), and the coupling
constants are in hertz. For 13C NMR, CDCl3 (δ 77.27) was
used as the internal standard, and spectra were obtained
with complete proton decoupling. Mass spectra were
recorded on an Agilent mass spectrometer in electrospray
ionization (ESI) mode. High-resolution mass spectra were
obtained on a WATERS Q-TOF Premier-HAB213 spec-
trometer in ESI mode.
7
4e
3g
3h
4d
3i
6
7
2-EtOOCC6H4
4-tBuC6H4
10
10
12
5
8
3-Pyridyl
9
10
2-MeO-4-pyridyl
8-Quinolinyl
6
4i
3k
4j
12
13
15
11
Aliphatic
–
DBU: 1,8-diazabicyclo[5.4.0]undec-7-ene; DMF: dimethyl formamide; RT:
room temperature.
aReaction conditions: alcohol (1.0mmol); 2, 2a (1.5mmol); and MnO2
(10mmol) in DMF (1.5mL) in the presence of DBU (1.5mmol) at RT for
5–15h.
bIsolated yield after chromatographic purification.
cnp: No product formation was observed.
General experimental procedures for the
synthesis of N-sulfinyl imines 3 and 4
Scheme 1. N-Sulfinyl ketimine formation.
In a round-bottom flask, to aldehyde (1.0mmol) in DMF
(1mL) was added sulfinamide (2 or 2a) (1.5mmol) fol-
lowed by DBU (1.5mmol). The solution was allowed to stir
at room temperature for 2–10h. The progress of the reac-
tion was monitored by TLC. After complete conversion, the
reaction mixture was diluted with ethyl acetate and washed
with water. The organic layer was dried over anhydrous
sodium sulfate, filtered, and evaporated. The crude product
was subjected to column chromatography on silica gel (elu-
ent: petroleum ether/ethyl acetate=80:20) to provide the
corresponding N-sulfinyl imines.
corresponding imines 3i and 4i. Bicyclic (quinolin-8-yl)
methanol (Table 4, entry 10) provided imines 3k and 4j in
76% and 70% yields, respectively. Unfortunately, the one-
pot synthesis under optimum conditions using aliphatic alco-
hols was unsuccessful (Table 4, entry 11).
Our efforts toward the formation of (S)-(tert-butane-
sulfinyl) imine under standardized conditions using acetophe-
none (1a) were unsuccessful. When we switched to toluene as
the solvent and heated the reaction mixture at 120°C for 3h,
product 5 was obtained in 28% isolated yield, and no remark-
able change was noted in the conversion beyond 3h or even at
higher temperatures (Scheme 1).
General experimental procedures for the one-
pot synthesis of N-sulfinyl imines 3 and 4
In a round-bottom flask, to alcohol (1.0mmol) and manga-
nese dioxide (10mmol) in DMF (1.5mL), was added sulfi-
Conclusion
In conclusion, we have established DBU as an efficient rea- namide (2 or 2a) (1.5mmol) followed by DBU (1.5mmol).
gent for the condensation of sulfinamides with aldehydes to The suspension was allowed to stir at room temperature for

6
Journal of Chemical Research 00(0)
5–15h. The progress of the reaction was monitored by TLC. J=8.8Hz, 2H), 7.48 (d, J=8.0Hz, 2H), 1.33 (s, 9H), 1.24
After complete conversion, the reaction mixture was filtered (s, 9H). 13C NMR (100MHz, CDCl3): δ 162.4, 156.1,
through a celite pad and washed with portions of ethyl ace- 131.5, 129.2, 125.8, 57.6, 35.1, 31.0, 22.5. MS (ESI): m/z
tate. The organic layer was washed with water, dried over 266.0 [M+H]+.
anhydrous sodium sulfate, filtered, and evaporated. The
(S)-2-Methyl-N-(pyridin-3-ylmethylene)propane-
crude product was subjected to column chromatography on 2-sulfinamide (3i):22 Pale yellow liquid; Yield: 94%; 1H
silica gel (eluent: petroleum ether/ethyl acetate=80:20) to NMR (400MHz, CDCl3): δ 9.02 (s, 1H), 8.71-8.70 (m,
provide the corresponding N-sulfinyl imines.
1H), 8.62 (s, 1H), 8.14 (d, J=8.0Hz, 1H), 7.42-7.39 (m,
(S)-N-Benzylidene-2-methylpropane-2-sulfinamide 1H), 1.26 (s, 9H). 13C NMR (100MHz, CDCl3): δ 160.3,
(3a):22 Colorless liquid; Yield: 87%; 1H NMR (400MHz, 152.8, 150.9, 135.7, 129.6, 123.9, 58.1, 22.5. MS (ESI):
CDCl3): δ 8.56 (s, 1H), 7.83-7.81 (m, 2H), 7.51-7.42 (m, m/z 211.1 [M+1]+.
3H), 1.24 (s, 9H). 13C NMR (100MHz, CDCl3): δ 162.7,
134.0, 132.4, 129.3, 128.9, 57.7, 22.5. MS (ESI): m/z 210.0 2-methylpropane-2-sulfinamide (3j):26 Pale yellow solid;
[M+H]+.
Yield: 96%; m.p. 83–85°C; 1H NMR (400MHz, CDCl3): δ
(S)-N-((5-Bromo-2-methoxypyridin-4-yl)methylene)-
(S)-N-(4-Methoxybenzylidene)-2-methylpropane-2- 8.79 (s, 1H), 8.32 (s, 1H), 7.24 (s, 1H), 3.9 (3, 3H), 1.22 (s,
sulfinamide (3b):22 Off-white solid; Yield: 81%; m.p. 90– 9H). 13C NMR (100MHz, CDCl3): δ 163.7, 160.5, 149.9,
92°C; 1H NMR (400MHz, CDCl3): δ 8.48 (s, 1H), 7.77 (d, 141.2, 113.1, 110.2, 58.5, 54.1, 22.6. MS (ESI): m/z 321.0
J=9.2Hz, 2H), 6.94 (d, J=9.2Hz, 2H), 3.83 (s, 3H), 1.22 [M+2]+.
(s, 9H). 13C NMR (100MHz, CDCl3): δ 163.0, 161.7,
131.2, 127.2, 114.3, 57.5, 55.4 22.5. MS (ESI): m/z 240.1 2-sulfinamide (3k):27 White solid; Yield: 85%; m.p. 80–
[M+H]+.
82°C; 1H NMR (400MHz, CDCl3): δ 10.06 (s, 1H),
(S)-2-Methyl-N-(quinolin-8-ylmethylene)propane-
(S)-N-(4-Cyanobenzylidene)-2-methylpropane-2- 8.99-8.98 (m, 1H), 8.45 (d, J=7.2Hz, 1H), 8.17 (d,
sulfinamide (3c):23 Off-white solid; Yield: 92%; m.p. 96– J=8.0Hz, 1H), 7.97 (d, J=8.4Hz, 1H), 7.64-7.60 (m, 1H),
98°C; 1H NMR (400MHz, CDCl3): δ 8.59 (s, 1H), 7.93 (d, 7.46-7.43 (m, 1H), 1.29 (s, 9H). 13C NMR (100MHz,
J=8.4Hz, 2H), 7.75 (d, J=8.0Hz, 2H), 1.25 (s, 9H). 13C CDCl3): δ 161.0, 150.8, 146.5, 136.0, 132.1, 131.2, 128.5,
NMR (100MHz, CDCl3): δ 161.0, 137.3, 132.7, 129.5, 128.2, 126.1, 121.7, 57.8, 22.7. MS (ESI): m/z 261.1
118.0, 115.4, 58.3, 22.6. MS (ESI): m/z 235.1 [M+H]+.
[M+H]+.
(S)-N-(Furan-3-ylmethylene)-2-methylpropane-2-
(S)-N-(2-Fluorobenzylidene)-2-methylpropane-2-
sulfinamide (3d):24 Colorless liquid; Yield: 83%; 1H NMR sulfinamide (3l):22 Off-white solid; Yield: 91%; m.p. 114–
(400MHz, CDCl3): δ 8.85 (s, 1H), 7.96-7.92 (m, 1H), 7.45- 116°C; 1H NMR (400MHz, CDCl3): δ 8.50 (s, 1H), 7.86
7.43 (m, 1H), 7.20-7.16 (m, 1H), 7.12-7.07 (m, 1H), 1.22 (s, 1H), 7.44 (s, 1H), 6.79 (s, 1H), 1.19 (s, 9H). 13C NMR
(s, 9H). 13C NMR (100MHz, CDCl3): δ 163.8, 161.2, (100MHz, CDCl3): δ 154.3, 147.6, 144.6, 124.2, 107.8,
156.5, 156.4, 134.1 (d, J=35.2Hz), 128.6, 124.5, 124.4, 57.4, 22.4. MS (ESI): m/z 200.1 [M+H]+.
122.0, 121.9, 116.3, 116.1, 57.8, 22.5. MS (ESI): m/z 228.1
[M+H]+.
(S)-N-(Cyclopropylmethylene)-2-methylpropane-2-
sulfinamide (3m):22 Colorless liquid; Yield: 90%; 1H
(S)-N-(4-Fluorobenzylidene)-2-methylpropane-2- NMR (400 MHz, CDCl3): δ 7.43 (d, J = 7.6 Hz, 1H),
sulfinamide (3e):22 Colorless liquid; Yield: 87%; 1H NMR 1.99-1.94 (m, 1H), 1.17 (s, 9H), 1.09-1.06 (m, 2H), 0.93-
(400MHz, CDCl3): δ 8.48 (s, 1H), 7.81-7.77 (m, 2H), 7.10- 0.55 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 171.7,
7.06 (m, 2H), 1.19 (s, 9H). 13C NMR (100MHz, CDCl3): δ 56.5, 22.1, 22.0, 17.5, 8.5, 8.4. MS (ESI): m/z 174.0
166.4, 163.9, 161.3, 131.4 (d, J=35.2Hz), 130.4, 116.2, [M + H]+.
116.0, 57.6, 22.5. MS (ESI): m/z 228.1 [M+H]+.
(S)-N-(Cyclohexylmethylene)-2-methylpropane-2-
(S)-N-(3-Bromobenzylidene)-2-methylpropane-2- sulfinamide (3n):22 Pale yellow liquid; Yield: 88%; 1H
sulfinamide (3f):25 Colorless liquid; Yield: 92%; 1H NMR NMR (400MHz, CDCl3): δ 7.91 (d, J=4.8Hz, 1H), 2.46-
(400MHz, CDCl3): δ 8.50 (s, 1H), 7.99 (s, 1H), 7.71(d, 2.38 (m, 1H), 1.90-1.80 (m, 2H), 1.78-1.72 (m, 2H), 1.68-
J=7.6Hz, 1H), 7.61 (d, J=8.4Hz, 1H), 7.35-7.31 (m, 1H), 1.60 (m, 2H), 1.32-1.25 (m, 4H), 1.14 (s, 9H). 13C NMR
1.24 (s, 9H). 13C NMR (100MHz, CDCl3): δ 161.3, 135.8, (100MHz, CDCl3): δ 172.7, 56.4, 43.9, 29.2, 25.8, 25.3
135.2, 131.5, 130.4, 128.3, 123.1, 58.0, 22.6. MS (ESI): (2C), 22.3. MS (ESI): m/z 216.0 [M+H]+.
m/z 290.0 [M+2]+.
(S)-N-(2,2-Dimethylpropylidene)-2-methylpropane-2-
(S)-Ethyl 2-(((tert-butylsulfinyl)imino)methyl) benzoate sulfinamide (3o):24 Colorless liquid; Yield: 91%; 1H NMR
(3g): Pale yellow liquid; Yield: 90%; 1H NMR (400MHz, (400MHz, CDCl3): δ 7.89 (s, 1H), 1.15 (s, 9H), 1.13 (s,
CDCl3): δ 9.22 (s, 1H), 8.0 (d, J=3.6Hz, 1H), 7.93 (d, 9H). 13C NMR (100MHz, CDCl3): δ 175.6, 56.4, 37.9,
J=7.6Hz, 1H), 7.57-7.52 (m, 2H), 4.39 (q, J=6.8Hz, 2H), 26.6, 22.3. MS (ESI): m/z 190.0 [M+H]+.
1.39 (d, J=7.6Hz, 3H), 1.37 (s, 9H). 13C NMR (100MHz,
(S)-N-((E)-Hex-2-en-1-ylidene)-2-methylpropane-2-
CDCl3): δ 166.5, 162.6, 134.3, 131.9, 131.7, 131.2, 130.4, sulfinamide (3p):28 Colorless semi-solid; Yield: 83%; 1H
128.7, 61.8, 57.8, 22.6, 14.21. HRMS (ESI) m/z: Calcd for NMR (400MHz, CDCl3): δ 8.13 (d, J=8.8Hz, 1H), 6.54-
C14H19NO3S [M+H]+: 281.3706, found: 282.0648.
6.46 (m, 1H), 6.40-6.35 (m, 1H), 2.22 (q, J=7.2Hz, 2H)
(S)-N-(4-(tert-Butyl)benzylidene)-2-methylpropane- 1.52-1.43 (m, 2H), 1.15 (s, 9H), 0.09 (t, J=8.0Hz, 3H).
2-sulfinamide (3h):24 White solid; Yield: 80%; m.p. 72– 13C NMR (100MHz, CDCl3): δ 164.1, 151.5, 128.7, 57.1,
75°C; 1H NMR (400MHz, CDCl3): δ 8.55 (s, 1H), 7.77(d, 34.9, 22.4, 21.4, 13.6. MS (ESI): m/z 202.0 [M+H]+.

Ramaiah et al.
7
(S)-N-Benzylidene-4-methylbenzenesulfinamide (4a):29 2H), 6.78 (s, 1H), 2.36 (s, 3H). 13C NMR (100MHz,
Off-white solid; Yield: 81%; m.p. 78–90°C; 1H NMR CDCl3): δ 152.4, 148.0, 144.7, 141.8, 141.7, 129.8, 124.7,
(400MHz, CDCl3): δ 8.74 (s, 1H), 7.83 (d, J=6.8Hz, 2H), 124.0, 107.9, 21.4. MS (ESI): m/z 234.0 [M+H]+.
7.62 (d, J=8.0Hz, 2H), 7.48-7.41 (m, 3H), 7.29 (d,
(S)-N-((2-Methoxypyridin-4-yl)methylene)-4-methyl
J=8.0Hz, 2H), 2.37 (s, 3H). 13C NMR (100MHz, CDCl3): benzenesulfinamide (4i): Off-white solid; Yield: 85%; m.p.
δ 160.6, 141.8, 141.7, 133.8, 132.5, 129.8, 129.5, 128.8, 116–118°C; 1H NMR (400MHz, CDCl3): δ 8.65 (s, 1H),
124.7, 21.3. MS (ESI): m/z 244.0 [M+H]+.
8.24 (d, J=5.6Hz, 1H), 7.60 (d, J=8.0Hz, 2H), 7.30-7.24
(S)-N-(4-Methoxybenzylidene)-4-methylbenzene- (m, 3H), 7.07 (s, 1H), 3.94 (s, 3H), 2.39 (s, 3H). 13C NMR
sulfinamide (4b):29 Off-white solid; Yield: 78%; m.p. 135– (100MHz, CDCl3): δ 164.9, 158.9, 147.8, 142.9, 142.0,
136°C; 1H NMR (400MHz, CDCl3): δ 8.65 (s, 1H), 7.78 (d, 130.1, 129.9, 125.7, 124.7, 115.0, 111.2, 53.8, 21.4. HRMS
J=8.8Hz, 2H), 7.61 (d, J=8.4Hz, 2H), 7.28 (d, J=8.0Hz, (ESI) m/z: Calcd for C14H14N2O2S [M]+: 274.3382, found
2H), 6.93 (d, J=8.4Hz, 2H) 3.84 (s, 3H), 2.37 (s, 3H). 13C 274.0635.
NMR (100MHz, CDCl3): δ 163.1, 159.7, 141.5, 131.5,
129.7, 127.0, 124.8, 115.7, 114.2, 55.4, 21.3. MS (ESI): m/z namide (4j): Off-white solid; Yield: 81%; m.p. 128–130°C;
274.0 [M+H]+.
1H NMR (400MHz, CDCl3): δ 10.22 (s, 1H), 8.96-8.94 (m,
(S)-4-Methyl-N-(quinolin-8-ylmethylene)benzenesulfi-
(S)-N-(4-Cyanobenzylidene)-4-methylbenzene- 1H), 8.39 (d, J=7.2Hz, 1H), 8.13-8.11 (m, 1H), 7.91 (d,
sulfinamide (4c):29 Off-white solid; Yield: 85%; m.p. 158– J=8.0Hz, 1H), 7.68 (d, J=8.0Hz, 2H), 7.56-7.53 (m, 1H),
160°C; 1H NMR (400MHz, CDCl3): δ 8.75 (s, 1H), 7.92 7.43-7.40 (m, 1H), 7.27 (d, J=8.0Hz, 2H), 2.35 (s, 3H).
(d, J=8.0Hz, 2H), 7.73 (d, J=8.0Hz, 2H), 7.61 (d, 13C NMR (100MHz, CDCl3): δ 158.9, 150.8, 146.5, 142.0,
J=8.0Hz, 2H), 7.31 (d, J=7.6Hz, 2H), 2.39 (s, 3H). 13C 141.5, 136.1, 132.4, 130.9, 129.8, 128.9, 128.1, 126.1,
NMR (100MHz, CDCl3): δ 190.6, 158.7, 142.1, 140.8, 124.8, 121.7, 21.4. HRMS (ESI) m/z: Calcd for C17H14N2OS
137.2, 132.9, 132.6, 130.0, 129.8, 124.6, 118.0, 115.6, 21.4. [M+H]+: 294.3709, found 295.0641.
MS (ESI): m/z 268.9 [M+H]+.
(S)-N-(4-(tert-Butyl)benzylidene)-4-methylbenzene Acknowledgements
sulfinamide (4d): Off-white solid; Yield: 80%; m.p. 108–
The authors wish to thank Srinivasaiah and Krishna Koushik for
110°C; 1H NMR (400MHz, CDCl3): δ 8.72 (s, 1H), 7.77
(d, J=8.4Hz, 2H), 7.61 (d, J=8.4Hz, 2H), 7.46 (d,
J=8.4Hz, 2H), 7.28 (d, J=8.0Hz, 2H), 2.38 (s, 3H), 1.32
(s, 9H). 13C NMR (100MHz, CDCl3): δ 160.3, 156.4,
142.0, 141.6, 131.3, 129.8, 129.4, 125.9, 124.8, 35.1, 31.1,
21.4. HRMS (ESI) m/z: Calcd for C18H21NOS [M+H]+:
299.4304, found: 300.1168.
their support.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
(S)-N-(3-Bromobenzylidene)-4-methylbenzene-
sulfinamide (4e):17 White solid; Yield: 91%; m.p. 94–
96°C; 1H NMR (400MHz, CDCl3): δ 8.66 (s, 1H), 8.00
(s, 1H), 7.70 (d, J=8.4Hz, 1H), 7.62-7.60 (m, 3H), 7.33-
7.29 (m, 3H), 2.38 (s, 3H). 13C NMR (100MHz, CDCl3):
δ 159.1, 141.9, 141.3, 135.6, 135.3, 131.7, 130.4, 129.9,
128.5, 124.7, 123.1, 21.4. MS (ESI): m/z 322.0 [M]+.
(S)-N-(2-Hydroxybenzylidene)-4-methylbenzene-
sulfinamide (4f):29 White solid; Yield: 82%; m.p. 110–
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
ORCID iD
Priya Babu Shubha
https://orcid.org/0000-0003-3751-3435
Supplemental material
112°C; 1H NMR (400MHz, CDCl3): δ 10.85 (s, 1H), 8.83 Supplemental material for this article is available online.
(s, 1H), 7.58 (d, J=8.4Hz, 2H), 7.45-7.38 (m, 2H), 7.31(d,
J=8.0Hz, 2H), 6.97-6.94 (m, 2H), 2.39 (s, 3H). 13C NMR References
(100MHz, CDCl3): δ 162.9, 160.2, 142.4, 141.4, 134.8,
133.4, 130.1, 125.7, 124.4, 119.8, 118.1, 117.3, 21.4. MS
(ESI): m/z 260.0 [M+H]+.
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