13C NMR EXAMPLES.......Ethyl cyanoacetate

C5H7O2N

. IUPAC Name: ethyl cyanoacetate   The peak is a singlet, indicating that it corresponds to a carbon bearing no hydrogens. The chemical shift (d 172) suggests that the carbon is a carbonyl, most likely a carboxylic acid or ester.       The peak is a singlet, indicating that it corresponds to a carbon bearing no hydrogens. The chemical shift (d 118) is in the region often observed for alkenes, alkynes adjacent to electron withdrawing groups and for nitriles.   The peak is a triplet, indicating that it corresponds to a CH2 group. The chemical shift (d 59) suggests that the CH2 is adjacent to an electronegative atom (i.e., oxygen). - O - CH2-     The peak is a triplet, indicating that it corresponds to a CH2 group. The chemical shift (d 22) suggests that the CH2 is adjacent to something mildly electronegative (i.e., a carbonyl), or is shielded by an adjacent sp-p system.        The peak is a quartet, indicating that it corresponds to a CH3 group. The chemical shift (d 14) is in the "simple" range, suggesting a simple terminal CH3 adjacent to something like a CH2. - CH2 - CH3     Analysis : Molecular formula and index of hydrogen deficiency C5H7O2N The index of hydrogen deficiency is 3, (3 degrees of unsaturation). Interpret : d (ppm) Multiplicity (n + 1) Indicating 172 singlet 118 singlet 59 triplet - O - CH2- 22 triplet 14 quartet - CH2 - CH3 ///////

13C NMR EXAMPLES........1,2-dimethoxyethane

IUPAC Name: 1,2-dimethoxyethane 

C4H10O2

. The peak is a triplet, indicating that it corresponds to a CH2. The chemical shift (d 80) suggests that the CH2 is adjacent to an electron-withdrawing group, such as an oxygen, and may be further shifted due to steric effects. - O - CH2-       The peak is a quartet, indicating that it corresponds to a CH3 group. The chemical shift (d 54) suggests that the CH3 is adjacent to an electronegative atom (i.e., oxygen). Note that there are only two peaks in the spectrum, but there are four carbons in the molecular formula. - O - CH3        Analysis : Molecular formula and index of hydrogen deficiency C4H10O2 The index of hydrogen deficiency is zero (no double bonds or rings). Interpret : d (ppm) Multiplicity (n + 1) Indicating 80 triplet - O - CH2 - 54 quartet - O - CH3 The 13C NMR has two peaks, a quartet at d 54 (a CH3) and a triplet at d 80 (a CH2). Since the molecule has four carbons and only two 13C NMR peaks, there must be symmetry. Both peaks are in the regions where carbons next to electronegative atoms occur (oxygen). 10 Best Restaurants in Chinatown Singapore Where to eat in Chinatown Singapore Chinatown Singapore has an excellent variety of restaurants, ranging from outdoor diners where you can sample some of the city’s best street food to places that frequently make lists of the world’s very best restaurants. Whether you’re looking to spend a couple of dollars or a few hundred, there’s something for every price point. Chinatown Singapore has a wonderful atmosphere, the pace is slightly slower than the rest of the city and the charming shophouses are home to some of the best restaurants in the city. Popular with visitors and locals, the area is always busy around dinner time. We’ve put together a list of our 10 best restaurants in Chinatown to help you make a decision! Although its appearance may be humble, Restaurant André, which seats 30 diners, is the epitome of a fine-dining experience. As exclusive as it gets, there’s only one menu, created by Chef André and his team based on the seasons and availability. The eight-course degustation menu is prepared from market-fresh and imported ingredients that the chef hand-picks each morning. Each creation has a Mediterranean essence, but the presentation is French-inspired. If you’re in luck, the foie gras jelly will be on the menu du jour, an unusual and original house speciality. Restaurant André is also well-known for their excellent wine list which is sourced from small, independent vineyards around the world. Read More... 2 Maxwell Hawker Centre One of the oldest hawker centres in Singapore, Maxwell Road Food Centre stands at the corner of South Bridge Road and Maxwell Road. Picking a dish here can be difficult; there are over 100 stalls and everything looks so tempting, so turn up hungry! The locals flock here for some of the best hawker food in town such as chicken rice, tapioca pastries, meat fritters and pork porridge. Gordon Ramsey raves about Tian Tian Chicken Rice, which is said to be one of the best versions of this Hainanese favourite in the city. Lunchtime can be intimidating with long queues for food, so arrive outside peak hours if you 3 Duxton Hill The rebirth of Duxton Hill has created a new foodie street in Chinatown. New restaurants have opened in quaint shop houses and cool bars keep springing up in a neighbourhood whose reputation used to be far from squeaky clean. It’s now a real pleasure to walk around Duxton Hill, down tree lined lanes where you will also find independent boutiques and quirky cafes. Despite being so popular, it really has a village feel to it, and makes a great place for a night out. Head up the hill to the end of the road, this area is cobbled and car-free. The restaurants here include an Italian trattoria, seafood specialist and French steakhouse, and have outdoor seating. Read More... 4 Chinatown Food Street or Smith Street Closed to traffic at dusk, Smith Street takes on a gregarious personality to the delight of visitors. Traditional Chinese lanterns the streets, and the busy area has a genuine buzz to it thanks to the crowds who come for supper, sitting on the small plastic stools that line the road. Navigate your way through more than a dozen stalls under iridescent neon lights and take your pick of popular street favourites. There’s plenty to pick from: fresh seafood, wok-fried noodles, crispy duck and steamed dim sum. Not only is the food extremely tasty but the prices are extremely affordable (starting at 3 SGD a dish), so you can try a bit of everything. Read More... 5 Tippling Club This attractive restaurant and cocktail bar draws you into to their wondrous world with a traditional exterior which takes over three shophouses and a quirky design inside. There’s plenty of comfortable bistro style seating around the open kitchen and the friendly face behind the bar is one of the city’s top mixologists who creates out of this world cocktails. The food is innovative, and to get the best of the chef’s creations try the tasting menu, which includes razor clams with purple garlic, venison and an interpretative dessert based on Terry’s Chocolate Orange. Without pairing the menu is 160 SGD. Read More... 6 Burnt Ends This Australian barbeque joint is an unusual concept in Singapore, and for this reason, alongside their delicious food, Burnt Ends packs in the crowds almost every night. At the centre of this restaurant is a large double-door oven that burns apple and almond wood, adding a smoky flavour. If you’re coming in a group with less than six people you’ll sit on the long counter, a front seat view of the action. There’s everything from pulled-pork burgers to a whole char grilled redfish, and even a smoked ice-cream for dessert. They don’t encourage bookings so you might have to wait, but if you’re a meat lover then it’s really worth it. Read More... 7 Majestic Restaurant On the ground floor of the New Majestic Hotel, the retro-chic Majestic Restaurant is renowned for its take on modern Cantonese cuisine served in individual portions. Its dishes are well executed and include popular options such as the crispy prawn with wasabi dressing, Peking duck served with pan-seared foie gras and double-boiled lobster broth with lobster meat, asparagus and mushrooms and fried carrot cake. The restaurant has combined the best of modern and traditional when it comes to the décor as well, with a modern, wood-lined dining space and traditional crockery and place settings. 8 Yum Cha For all-day dining in the heart of Chinatown, Yum Cha is the place to go. On the second level of an old shophouse, Yum Cha, which means ‘drink tea’, is the quintessential experience for a Chinatown dining experience. Besides the shark fin soup, fried beef noodles, champagne pork ribs, spicy lamb rack and other specials, it is known for its dim sum dishes which are also offered in a daily high tea buffet. 9 Lee Tong Kee Ipoh Hor Fun Restaurant A quaint rice noodle shop with its roots in Ipoh, Malaysia, this outlet is ideal for a quick meal in a comfortable setting. Its staple is the homemade ‘hor fun’ or rice noodles served in tasty gravy with chicken and prawn. Other specialty dishes are the crunchy bean sprouts with cuttlefish, wonton soup and chicken claws with mushroom. Its freshly squeezed lime juice and avocado blended with gula melaka (palm sugar) has been winning fans for years. 10 Yixing Xuan Teahouse Yixing Xuan Teahouse sits behind one of the picturesque old-fashioned shop-house fronts in the heart of Chinatown, offering some of the finest Chinese tea and appreciation classes to those who want a taste of days gone by. Staff members are welcoming and will give you a much deeper understanding of the history and culture of tea drinking and its ceremonies. The small restaurant alongside the tea room makes great dim sum and a decent variety of Chinese dishes including the extraordinary tealeaf chicken – a great way of turning their highlight. Be sure to try their house tea, ‘Beauty of the East’ which is fresh and light. You can also admire pictures of Queen Elizabeth whilst you dine. She made a stop here in 1991 on her state visit. ///////

N-(4-hydroxyphenyl)mandelamide

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The chiral N-(4-hydroxyphenyl)mandelamide (1) was synthesized through condensation of p-aminophenol with (R)- or (S)-mandelic acid, respectively in presence of dicyclohexylcarbodiimide as condensing agent. For oligomerization of 1 via oxidative coupling laccase from Pleurotus ostreatus, peroxidase from horseradish or iron(II)-salen were used as catalysts. The obtained yellow powdery oligomers 2 show high solubility in many commonly used organic solvents like acetone, THF, ethanol, methanol, acetonitrile and 1,4-dioxan. Because of the broad signals of the oligomers 2 in the ¹H NMR spectra the ratio of the phenylene and oxyphenylene units (Scheme 1) could not be clearly determined.

Scheme 1: Oligomerization of N-(4-hydroxyphenyl)mandelamide (1).

The oligomerization of 1 in water could be easily performed through complexation of the monomer 1 with randomly methylated β-cyclodextrin (RAMEB-CD). The formation of the complex was verified with 2D ROESY NMR spectroscopy. The magnetic interaction of the monomer with the cavity of RAMEB-CD is obvious in the 2D ROESY NMR spectra as shown in Figure 1 (marked areas). Principally, cyclodextrins and their derivatives are able to discriminate enantiomeric compounds [9,10]. Such chirality recognition is provable with ¹H NMR spectroscopy because of the different induced shift of the protons which became diastereotopic through complexation [11,12]. Actually, the chirality discrimination of 1 with RAMEB-CD is evident from the different induced shift of the protons 8 at 5.2 ppm (zoomed out in Figure 1).

Figure 1: 2D ROESY NMR spectrum (600 MHz, D₂O) of the racemate 1 complexed with RAMEB-CD.

The MALDI–TOF MS measurements indicate the formation of oligomers 2 from the monomer 1 as shown in Figure 2. As expected the repetitive unit has a molecular mass of 241 g/mol, which confirms the linkage of the monomers via a formal abstraction of two hydrogen atoms. The highest molecular weight oligomers 2 obtained through enzymatic oligomerization consists of up to 10 repetitive units which could be detected by MALDI–TOF MS measurements. Furthermore comparable molecular weights are accessible through oligomerization of 1 with iron(II)-salen as catalyst. Here oligomers 2 with up to 8 repetitive units are detectable.

Figure 2: MALDI–TOF MS spectrum of the oligomers synthesized with laccase from the racemate 1.

The conversion of the enantiomers of 1 during the enzymatic oligomerization has been studied using chiral HPLC. Accordingly, the racemate of 1 was oligomerized three times with each enzyme in the absence of RAMEB-CD or in the presence of RAMEB-CD, respectively to evaluate the reproducibility. The isolated monomeric residual of each oligomerization was measured twice. The obtained enantiomeric excess (ee) values of the monomeric residual are given in Table 1. Because of the rapid conversion of the monomer 1 during the oligomerization with highly active peroxidase–H₂O₂ system at room temperature, the reaction time was limited to one minute at 0 °C. In the presence of the lower active laccase–O₂ system, the reaction was carried out for 4 h at room temperature.

Table 1: Enantiomeric excess values (ee) of the monomeric residual of the enzymatic oligomerization of 1.

used enzyme, use of CD	ee (%)a
laccase	racemic mixture
peroxidase	6 S
laccase + CD	4 R
peroxidase + CD	8 R
aCalculated on the basis of the surfaces of chiral HPLC peaks, enantiomers were separated from the reaction mixture by column chromatography with ethylacetate/n-hexane (2:1) as eluent.

In the absence of RAMEB-CD it is apparent that laccase shows no enantioselectivity. However it can be established that during the oligomerization with peroxidase the (S)-enantiomer 1 slightly enriches the reaction solution. Additionally to that, it was of some interest to verify, whether the complexation of the enantiomers with RAMEB-CD affects the conversion of the enantiomers. Therefore, the relatively slow oligomerizations in the presence of laccase were carried out in pH 5 buffer at room temperature for 4 hours. The rapid oligomerizations in the presence of peroxidase were carried out in pH 7 buffer at 0 °C for 1 min. It was found that, in the presence of RAMEB-CD, the (R)-enantiomer of 1 slightly enriches the reaction mixture with laccase as well as with peroxidase. As already mentioned above, the opposite effect was observed when the oligomerization was carried out with peroxidase without using RAMEB-CD. However, the obtained data show that the degree of enantioselectivity during conversion of 1 is generally very low.

Syntheses

Synthesis of N-(4-hydroxyphenyl)mandelamide (1)

7.61 g (50 mmol) Mandelic acid and 5.75 g (50 mmol) N-hydroxysuccinimide were dissolved in 150 mL acetone and cooled in an ice–water bath. Subsequently, a suspension of 10.32 g (50 mmol) dicyclohexylcarbodiimide in 50 mL acetone was added and the reaction mixture stirred for 2.5 hours at 0 °C. After that, 5.46 g (50 mmol) p-aminophenol was added and the ice bath was removed. The reaction mixture was stirred for 24 hours at room temperature. The precipitated dicyclohexylurea was filtered off. Then the solution was concentrated under reduced pressure and the product purified by column chromatography (eluent: n-hexane/ethyl acetate 1:2). Yield depending on the use of racemic or (S)-, (R)-enantiomer of mandelic acid: (RS)-1 = 9.16 g (75%), (S)-1 = 10.03 g (82%), (R)-1 = 9.63 g (79%). mp: (RS)-1: 97 °C, (S)-1: 155 °C, (R)-1: 153 °C; optical rotation (THF): (S)-1: [α]_D²⁰ −3,9°, (R)-1: [α]_D²⁰ +3,4°; (RS)-1: GC–EIMS, m/z: 243 [M(1)]⁺, 137, 109, 79. ¹H NMR (500 MHz, DMSO-d₆) δ 9.66 (s, 1H, -NH), 9.20 (s, 1H, -OH), 7.50 (d, 2H, -ArH), 7.46 (d, 2H, -ArH), 7.35 (t, 2H, -ArH), 7.28 (t, 1H, -ArH), 6.68 (d, 2H, -ArH), 6.35 (d, 1H, -OH), 5,055 (d, 1H, -CH) ppm; ¹³C NMR (75 MHz, DMSO-d₆) δ 170.42 (C=O), 153.52 (C-OH), 141.10, 130.17, 128.04, 127.51, 126.56, 121.39, 114.96 (Ar-C), 73.91 (C-OH) ppm.

Synthesis of oligo (N-(4-hydroxyphenyl)mandelamide) (2)

Enzymatic oxidative oligomerization with peroxidase: A solution of 7.5 mg peroxidase dissolved in 10 ml pH 7 buffer was added to a solution of 1.22 g (5 mmol) N-(4-hydroxyphenyl)mandelamide (1) and 40 mL 1.4-dioxan. 510 µL of hydrogen peroxide (30%) were added to the mixture in aliquots of 51 µL in 15 minutes intervals. After stirring for 2 h at room temperature, the product was precipitated by pouring into 0.5 M HCl and dried under vacuum. Yield depending on use of racemic or (S)-, (R)-enantiomer of N-(4-hydroxyphenyl)mandelamide (1): (RS)-2 = 0.79 g (65%), (S)-2 = 1.02 g (85%), (R)-2 = 0.97 g (80%). GPC (DMF): (RS)-2: M_n = 1500 g mol⁻¹, D = 1.22, (S)-2: M_n = 1510 g mol⁻¹, D = 1.21, (R)-2: M_n = 1500 g mol⁻¹, D = 1.23; (RS)-2: ¹H NMR (300 MHz, DMSO-d₆) δ 10.04–9.64 (broad signal, 1H, -NH), 7.79-6.71 (broad signal, 8H, -ArH), 6.52-6.13 (broad signal, 1H, -OH), 5.16-4.92 (broad signal, 1H, -CH) ppm.

Oligomerization of optically active N-(4-hydroxyphenyl)mandelamide in the presence of β-cyclodextrin and the minor role of chirality

Helmut Ritter¹, Antonia Stöhr¹ and Philippe Favresse²

¹Institute of Organic Chemistry and Macromolecular Chemistry, Heinrich-Heine-University Düsseldorf, Universitätsstraße 1, Düsseldorf, 40225, Germany
²Coatings & Additives, Evonik Industries AG, Goldschmidtstraße 100, Essen, 45127, Germany

Corresponding author email     

Associate Editor: S. C. Zimmerman

Beilstein J. Org. Chem. 2014, 10, 2361–2366.

 http://www.beilstein-journals.org/bjoc/single/articleFullText.htm?publicId=1860-5397-10-246
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DIMENSIONS IN NMR SPECTROSCOPY

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1D - NMR Spectrum

When we talk about an 1D-NMR spectrum, we mean a spectrum (2-dimensional graph) in which an abcissa axis shows the frequency (chemical shift) and an ordinate axis shows the intensity of peaks.

2D - NMR Spectrum

 When we talk about a two-dimensional spectrum, we mean a spectrum (3-dimensional graph) in which both abcissa and ordinate axes show chemical shifts and the third dimension shows the intensity of the peaks.

2-D J-resolved spectrum F1  scalar coupling F2  chemical shift	2D-correlated spectrum F1 & F2  chemical shift withn scalar spin-spin or dipolar copling a) 1H vs 1H b) 1H vs 13C

 Now many NMR techniques are now available for identifying molecular structures. Chemists can now clearly understand information about spin - spin coupling and the exact conectivity of atoms in molecules with techniques called multidimensional NMR spectroscopy. The most common techniques are two-dimensional NMR or 2D NMR such as COSY, HETCOR, and others.

When 2D NMR is applied to ¹H-NMR, it is called ¹H-¹H COrrelation SpectroscopY or COSY. COSY spectra are useful for deducing proton-proton coupling relationships.

2D spectra can be obtained to indicate coupling between hydrogens and the carbons to which they attached. In this case it is called ¹H-¹³C HETeronuclear CORrelation spectroscopy or HETCOR.

  In a COSY spectrum, a H ¹ spectrum is shown along both horizontal and vertical axes, and the intensity of correlation peaks is shown as mountains.

The important information from the COSY spectrum comes from the correlation peaks (mountains) that appear off the diagonal (cross peaks). If we start at a given cross peak and imagine that two perpendicular lines lead back to the diagonal, these lines are coupled to each other. The intersepted peaks indicate that they are coupled to each other. It is found that the cross peaks above the diagonal are found symmetrically so only cross peaks on one side of the diagonal need to be interpreted.

Example : COSY spectrum of geraniol
1. Basic COSY spectrum of geraniol, in CDCl₃ at 500 MHz
From the basic COSY spectrum, we can see that H-5 and H-6 are coupled by each other. However, the signals for 3 methyl groups at C-8, C-9, and C-10 are severely overlaped, as are those for the 2 methylene groups at C-4 and C-5. Moreover, it lacks of the H-1----H-4
and H-6----H-8 couplings, and the differentiation between H-8 and H-9 is uncertain.
These problems can be less by using a double quantum filtered COSY (DQFCOSY); the intense singlets of noncoupled methyl groups are greatly reduced.

2. The DQFCOSY spectrum of geraniol, in CDCl₃ at 500 MHz
In the DQFCOSY spectrum, we can see that the H-8 and H-9 methyl proton signals are clearly separated. The long-range coupling of H-8 and H-9 methyl groups with one another and the H-1----H-4 and H-6----H-8 couplings are present. However, the differentiation between H-8 and H-9 is still uncertain.

 The HETCOR experiment correlates ¹³C nuclei with attached ¹H nuclei; these are one-bond couplings.

In a HETCOR spectrum, a ¹³C spectrum is shown along one axist and a ¹H spectrum is shown along the other axist. The cross peaks that relate the two types of spectra to each other are found in the third dimension.

The cross peak indicates that the hydrogen giving rise to the ¹H NMR signal on one axist is coupled (and attached) to the carbon that giving rise to the corresponding ¹³C NMR signal on the other axist. Therefore, we can indicate which hydrogens are attached to which carbon in a molecule.

Example : HETCOR spectrum of geraniol

The HETCOR spectrum of geraniol, in CDCl₃ at 500 MHz for ¹H and 125.7 for ¹³C

We have the proton assigned from the COCY spectrum, so we can now correlate them with the carbon atoms in the HETCOR spectrum of geraniol. From high to low field in the ¹³C axis, we assign
       - the methyl groups 10, 8, and 9
       - the methylene 5, 4, and 1
       - the alkene methines 6 and 2
       - the quarternary carbon atoms 3 and 7 are not correlated with protons

1. Ipsenol

1.1 COSY spectrum of ipsenol

chemical shift (ppm)	indicated protons	correlations
6.35	olefinic	coupled to olefinic protons at d 5.08 ppm
5.08 (group)	olefinic	coupled to olefinic protons at d 5.35 ppm and methylene protons at d 2.22 and 2.48 ppm
3.83	carbinol methine	coupled to 4 protons corresponding to 2 adjacent methylene groups
2.48	methylene	coupled to carbinol methine proton and each other
2.22	methylene
1.82	isopropyl methine	coupled to 3 protons corresponding to 2 adjacent metnylene groups
1.80	hydroxylic	-
1.49	methylene	coupled to carbinol methine proton and each other
1.26	methylene
0.93	2 overlaping methyl doublets	coupled to isopropyl methine proton

1.2 HETCOR spectrum of ipsenol

13C chemical shift (ppm)	1H chemical shift (ppm)	indicated part of structure
143	-	olefinic (quarternary C)
138	6.35	olefinic
117, 119	5.08, 5.15	olefinic
117	5.24, 5.26	olefinic
69	3.83	carbinol methine
41	2.48, 2.22	methylene
25	1.82	isopropyl methine
-	1.80	hydroxylic
47	1.26, 1.49	methylene
22, 24	0.93	2 overlaping methyl doublets

2. Caryophyllene oxide 2.1 COSY spectrum of caryophyllene oxide 2.2 Expanded view of COSY spectrum of caryophyllene oxide        chemical shift (ppm) indicated protons correlations 4.99 olefinic coupled to each other 4.81 olefinic 2.86 methine coupled to 2 resonances at 1.28 and 2.23 ppm 2.60 allylic methine coupled to 3 resonances (methine 1.76 ppm and methylene 1.43, 1.47 ppm) 2.37, 2.11 methylene coupled to 2 resonances at 2.23 and 1.28 ppm 2.23, 1.28 methylene coupled to protons at 2.11, 2.37 and 2.86 ppm 2.06, 0.95 methylene coupled to 2 resonances at 1.45 and 1.63 ppm 1.76 methine coupled to proton at 1.45 ppm 1.63, 1.45 methylene coupled to 2 resonances at 0.95 and 2.06 ppm 1.47, 1.43 methylene coupled to allylic methine at 2.60 ppm 1.19 methyl - 1.01 methyl coupled to each other 0.98 methyl 2.3 HETCOR spectrum of caryophyllene oxide        13C chemical shift (ppm) 1H chemical shift (ppm) indicated part of structure 153 - quarternary C-8 113 4.81, 4.99 methylene C-12 63.6 2.86 methine C-5 59.7 - quarternary C-4 50.9 1.76 methine C-1 48.7 2.60 methine C-9 39.8 1.43, 1.47 methylene C-10 39.2 0.95, 2.06 methylene C-3 34.0 - quarternary C-11 30.1 1.28, 2.23 methylene C-6 30.0 not available methyl C-13 29.9 2.11, 2.37 methylene C-7 27.2 1.45, 1.63 methylene C-2 22.6 not available methyl C-14 or C-15 16.9 not available methyl C-14 or C-15

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